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__NOTOC__
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{{Pancytopenia}}
 
{{CMG}}'''; Associate Editor-In-Chief:''' {{CZ}}
'''''Pancytopenia is not equivalent with bone marrow suppression.  Pancytopenia is a lab finding that may related to either bone marrow suppression or peripheral sequestration/destruction.  For details about bone marrow suppression click [[bone marrow suppression|here]].'''''
{{SI}}
 
{{CMG}}; {{AE}} {{CZ}}, {{Ochuko}}, {{shyam}}, {{SSH}}


==Overview==
==Overview==
Pancytopenia is the reduction in numbers of all three bone marrow cell types, including [[red blood cells]], [[white blood cells]], and [[platelets]]. The prefix "pan-" means "everything," "cyto" means "cell", and the suffix "penia" means "deficiency." Pancytopenia is not a disease, but rather a laboratory finding that may related to bone marrow suppression caused by either insufficient production ([[aplastic anemia]]), inability of cells to mature ([[myelodysplasia]]), replacement of normal bone marrow with [[fibrosis]] ([[myelofibrosis]]) or peripheral sequestration that is not related to the [[bone marrow]] (e.g. [[splenomegaly]] or [[hypersplenism]]). Chemotherapy is associated with pancytopenia due to drug-mediated bone marrow suppression. Pancytopenia frequently requires a [[bone marrow biopsy]] in order to distinguish among different causes.


'''Pancytopenia''' is the pronounced reduction in the number of [[erythrocyte]]s, all types of [[white blood cell]]s and blood [[platelets]] that are circulating in the blood.  
==Historical Perspective==
 
The history of pancytopenia relates to the history of each of its individual sub-entities, namely [[anemia]], [[thrombocytopenia]], and [[leukopenia]]. Pancytopenia was not recognized as a distinct clinical entity until after each of its other subcomponents were characterized. Thus, there is no specific history for pancytopenia.
[[Pancytopenia]] is generally due to diseases affecting the [[bone marrow]], although peripheral destruction of all lines of blood cells in [[hypersplenism]] (overactive [[spleen]]) is a recognized cause. [[Bone marrow]] problems causing [[pancytopenia]] include [[myelofibrosis]], [[leukemia]], [[aplastic anemia]], and the malignant form of [[osteoporosis]].


Chemotherapy for malignancies may also cause [[pancytopenia]], if the drug or drugs used cause [[bone marrow]] suppression.   
*History of [[aplastic anemia]]:
**The seminal discoveries for [[aplastic anemia]] were made by Bruno Speck and Georges Mathe, who noted that immunosuppression could be used to treat aplastic anemia.<ref name="pmid19252172">{{cite journal| author=Passweg JR, Tichelli A| title=Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? | journal=Haematologica | year= 2009 | volume= 94 | issue= 3 | pages= 310-2 | pmid=19252172 | doi=10.3324/haematol.2008.002329 | pmc=2649354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19252172  }} </ref>
**In the 1970s, matched sibling donor transplant was used for severe aplastic anemia.<ref name="pmid22517900">{{cite journal| author=Scheinberg P, Young NS| title=How I treat acquired aplastic anemia. | journal=Blood | year= 2012 | volume= 120 | issue= 6 | pages= 1185-96 | pmid=22517900 | doi=10.1182/blood-2011-12-274019 | pmc=3418715 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22517900 }} </ref>


Increasingly, [[HIV]] ([[Human Immunodeficiency Virus]]) is itself a cause for [[pancytopenia]].
*History of [[paroxysmal nocturnal hemoglobinuria]]:
**In 1882, Dr. Paul Strubing reported the case of a patient with hematuria at night that occurred periodically.<ref name="pmid25237200">{{cite journal| author=Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria. | journal=Blood | year= 2014 | volume= 124 | issue= 18 | pages= 2804-11 | pmid=25237200 | doi=10.1182/blood-2014-02-522128 | pmc=4215311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25237200  }} </ref>
***He noted that hemolysis was the reason for the patient's hematuria.
**In 1925, the term paroxysmal nocturnal hemaglobinuria was coined.<ref name="pmid25237200">{{cite journal| author=Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria. | journal=Blood | year= 2014 | volume= 124 | issue= 18 | pages= 2804-11 | pmid=25237200 | doi=10.1182/blood-2014-02-522128 | pmc=4215311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25237200  }} </ref>
**In the 1930s, Dr. T.H. Ham noted that acidified serum could induce hemolysis.
***Thus, the Ham's acid serum test was developed.<ref name="pmid25237200">{{cite journal| author=Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria. | journal=Blood | year= 2014 | volume= 124 | issue= 18 | pages= 2804-11 | pmid=25237200 | doi=10.1182/blood-2014-02-522128 | pmc=4215311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25237200  }} </ref>
***This became the first diagnostic test for this disease.
**In the 1950s, the [[complement]] pathway was discovered, and it was determined that [[paroxysmal nocturnal hemoglobinuria]] was due to activation of [[complement]] proteins on the [[red blood cell]] membrane.<ref name="pmid25237200">{{cite journal| author=Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria. | journal=Blood | year= 2014 | volume= 124 | issue= 18 | pages= 2804-11 | pmid=25237200 | doi=10.1182/blood-2014-02-522128 | pmc=4215311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25237200  }} </ref>
**In the 1980s, the genetic defect responsible for the disease was discovered, specifically, the PIG-A gene defect leading to inability to anchor [[complement]]-inhibitory proteins onto the [[red blood cell]] membrane.


Rarely, drugs (antibiotics, anti hypertensive medication, heart medication) can cause [[pancytopenia]].
==Classification==
There is no classification system for pancytopenia. However, some underlying disease entities that cause pancytopenia have classification. For example, aplastic anemia is classified as moderate, severe, or very severe.


[[Pancytopenia]] usually requires a [[bone marrow]] [[biopsy]] in order to distinguish among different causes.
==Pathophysiology==
* The pathophysiology of pancytopenia relates to the underlying etiology. 
* In most cases, pancytopenia is due to a disruption in trilineage [[hematopoiesis]]. 
* This means that the bone marrow is not appropriately producing [[erythrocytes]], [[leukocytes]], and [[thrombocytocytes]]
* The cause of the disruption in trilineage [[hematopoiesis]] is in turn due to the underlying cause of pancytopenia. 
* For example, viral-mediated pancytopenia is caused by viral particles infecting [[Hematopoietic|hematopoietic cells]] and preventing normal cell division. 
* Leukemia-mediated pancytopenia is typically due to marrow replacement of normal hematopoietic precursors, a process known as myelopthisis. 
* Leukemic infiltration of the bone marrow creates a "crowding-out" phenomenon.  


==Causes==
==Causes==
===Life Threatening Causes===
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of pancytopenia that require acute treatment within 24 hours. However, if pancytopenia is accompanied by fever, this should be treated as a hematologic emergency with prompt administration of IV antibiotics.


===Common Causes===
===Common Causes===
 
* [[Aplastic anemia]] <ref name="pmid24353701">{{cite journal| author=Das Makheja K, Kumar Maheshwari B, Arain S, Kumar S, Kumari S| title=The common causes leading to pancytopenia in patients presenting to tertiary care hospital. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 5 | pages= 1108-11 | pmid=24353701 | doi= | pmc=PMC3858928 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353701  }} </ref>
# [[Aplastic anemia]]
** This is a condition characterized by immune-mediated reduction in all three hematopoietic cell lines with absence of hematopoietic precursors.<ref name="pmid19252172">{{cite journal| author=Passweg JR, Tichelli A| title=Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? | journal=Haematologica | year= 2009 | volume= 94 | issue= 3 | pages= 310-2 | pmid=19252172 | doi=10.3324/haematol.2008.002329 | pmc=2649354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19252172  }} </ref> 
 
** It is a rare condition with a prevalence of only 1-2 cases per million annually. It is most commonly diagnosed in childhood. 
# [[Myelodysplastic syndrome]]
** Epidemiologic studies have shown a greater prevalence in Southeast Asia and other countries with limited access to healthcare, as viral infection can trigger aplastic crisis.<ref name="pmid19252172">{{cite journal| author=Passweg JR, Tichelli A| title=Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? | journal=Haematologica | year= 2009 | volume= 94 | issue= 3 | pages= 310-2 | pmid=19252172 | doi=10.3324/haematol.2008.002329 | pmc=2649354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19252172  }} </ref> 
 
** There are three categories: moderate, severe, and very severe. 
# [[Leukemia]]
** These categories are based upon the number and degree of cytopenias as well as bone marrow cellularity. 
 
** The preferred treatment of aplastic anemia is bone marrow transplantation from an HLA-matched sibling. 
# [[Leishmaniasis]]
** If there is no [[human leukocyte antigen]] (HLA)-matched sibling available, the next best option is medical management with the immunosuppressive agents [[anti-thymocyte globulin]] ([[ATG]]) and [[cyclosporine A]].<ref name="pmid19252172">{{cite journal| author=Passweg JR, Tichelli A| title=Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? | journal=Haematologica | year= 2009 | volume= 94 | issue= 3 | pages= 310-2 | pmid=19252172 | doi=10.3324/haematol.2008.002329 | pmc=2649354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19252172  }} </ref> 
 
** The reason for the efficacy of immunosuppressive medications is that the pancytopenia from [[aplastic anemia]] is due to abnormal immune activation and thus destruction of hematopoietic cells. 
# Severe [[Folate]] or [[Vitamin B12 deficiency]]  
** [[ATG]] from horse has been shown to be superior compared to [[ATG]] from rabbit.<ref name="pmid19252172">{{cite journal| author=Passweg JR, Tichelli A| title=Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling? | journal=Haematologica | year= 2009 | volume= 94 | issue= 3 | pages= 310-2 | pmid=19252172 | doi=10.3324/haematol.2008.002329 | pmc=2649354 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19252172  }} </ref> 
 
** [[ATG]] is administered over 5 days, and [[cyclosporine A]] is administered orally for 6 months, after which response can be assessed. 
# [[Paroxysmal nocturnal hemoglobinuria]] ([[Urine test]])
** The combination of [[ATG]] and [[cyclosporine A]] carries a response rate of 60-70%. <ref name="pmid22517900">{{cite journal| author=Scheinberg P, Young NS| title=How I treat acquired aplastic anemia. | journal=Blood | year= 2012 | volume= 120 | issue= 6 | pages= 1185-96 | pmid=22517900 | doi=10.1182/blood-2011-12-274019 | pmc=3418715 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22517900  }} </ref> Eltrombopag can also be added to the regimen of ATG and cyclosporine.
 
* [[Folate deficiency]]
# Finally overwhelming [[viral infection]]s ([[HIV]] most common)
** Folate is required for pyrimidine nucleotide synthesis, and thus folate deficiency can lead to decreased production of hematopoietic cells.<ref name="pmid3671238">{{cite journal| author=Weston CF, Hall MJ| title=Pancytopenia and folate deficiency in alcoholics. | journal=Postgrad Med J | year= 1987 | volume= 63 | issue= 736 | pages= 117-20 | pmid=3671238 | doi= | pmc=2428237 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3671238  }} </ref>
** Folate deficiency occurs in persons who consume large amounts of alcohol.
** Folate deficiency is accompanied by [[macrocytosis]], or large-sized cells.
** Treatment of folate deficiency is supplementation of folate in the diet.
* [[Leishmaniasis]]
** This is a rare infectious cause of pancytopenia.
* [[Leukemia]]
** This can be myeloid or lymphoid, and each of these can be acute or chronic.
** Acute leukemias typically cause pancytopenia via a crowding-out phenomenon, known as [[myelopthisis]].
** Diagnosis of acute leukemia is based by demonstration of blast count of 20% or greater in the bone marrow.
** Treatment involves multiagent chemotherapy, such as [[cytarabine]] combined with [[anthracycline]] for [[acute myeloid leukemia]], or vincristine-based and anthracycline-based regimen for [[acute lymphoblastic leukemia]].
** Treatment of the underlying leukemia can help improve pancytopenia.
* [[Megaloblastic anemia]] <ref name="pmid24353701">{{cite journal| author=Das Makheja K, Kumar Maheshwari B, Arain S, Kumar S, Kumari S| title=The common causes leading to pancytopenia in patients presenting to tertiary care hospital. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 5 | pages= 1108-11 | pmid=24353701 | doi= | pmc=PMC3858928 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353701  }} </ref>
** This condition is characterized by decreased [[red blood cell]] count and increased cellular size with defective maturation.<ref name="pmid27780269">{{cite journal| author=Yadav MK, Manoli NM, Madhunapantula SV| title=Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0164559 | pmid=27780269 | doi=10.1371/journal.pone.0164559 | pmc=5079580 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27780269  }} </ref>
** The cause is usually deficiency of vitamin B12 or folate.
** The diagnosis is made with a [[complete blood count]] showing hemoglobin less than 12 g/dl, mean corpuscular volume greater than 100 femtoliter (MCV > 100 fL), and peripheral smear showing enlarged cells.
** The treatment is supplementation with vitamin B12 or folate.<ref name="pmid27780269">{{cite journal| author=Yadav MK, Manoli NM, Madhunapantula SV| title=Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0164559 | pmid=27780269 | doi=10.1371/journal.pone.0164559 | pmc=5079580 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27780269  }} </ref>
* [[Myelodysplastic syndrome]]
** This is a disease characterized by ineffective erythropoiesis and peripheral cytopenias.
** It is a clonal disorder of the [[hematopoietic stem cell]].<ref name="pmid22417201">{{cite journal| author=Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K et al.| title=Clonal architecture of secondary acute myeloid leukemia. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 12 | pages= 1090-8 | pmid=22417201 | doi=10.1056/NEJMoa1106968 | pmc=3320218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22417201  }} </ref>
** The subtype of myelodysplastic syndrome that causes pancytopenia is termed refractory anemia with multilineage dysplasia.
** The pancytopenia of myelodysplastic syndrome is due to failure of maturation of hematopoietic precursors, leading to peripheral cytopenias.<ref name="pmid22417201">{{cite journal| author=Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K et al.| title=Clonal architecture of secondary acute myeloid leukemia. | journal=N Engl J Med | year= 2012 | volume= 366 | issue= 12 | pages= 1090-8 | pmid=22417201 | doi=10.1056/NEJMoa1106968 | pmc=3320218 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22417201  }} </ref>
** Diagnosis of myelodysplastic syndrome is made by demonstration of at least 1 cell line with 10% of greater dysplastic cells on bone marrow biopsy.
** Bone marrow biopsy should also show myeloblasts less then 20% of total leukocytes.
** Clinical features of myelodysplastic syndrome include manifestations of specific cytopenias, such as fatigue if there is anemia, bleeding if there is thrombocytopenia, and infections if there is leukopenia.<ref name="pmid23954262">{{cite journal| author=Zeidan AM, Linhares Y, Gore SD| title=Current therapy of myelodysplastic syndromes. | journal=Blood Rev | year= 2013 | volume= 27 | issue= 5 | pages= 243-59 | pmid=23954262 | doi=10.1016/j.blre.2013.07.003 | pmc=4124605 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23954262  }} </ref>
** The prognostication of myelodysplastic syndrome is determined by the International Prognosis Scoring System-Revised (IPSS-R), which is determined by blast count, the karyotype, and cytopenia.
** This clinical tool is used to estimate the time to progression to acute myeloid leukemia.
** The treatment of myelodysplastic syndrome is based on the subtype. Lenalidomide is highly effective for persons with deletion of chromosome 5q.<ref name="pmid23954262">{{cite journal| author=Zeidan AM, Linhares Y, Gore SD| title=Current therapy of myelodysplastic syndromes. | journal=Blood Rev | year= 2013 | volume= 27 | issue= 5 | pages= 243-59 | pmid=23954262 | doi=10.1016/j.blre.2013.07.003 | pmc=4124605 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23954262  }} </ref>
** DNA hypomethylating agents like azacitadine and decitabine are commonly used for those with symptomatic cytopenias and without chromosome 5q deletion.
** In some cases, allogeneic stem cell transplantation can be done with the goal of curing myelodysplastic syndrome and preventing progression to acute myeloid leukemia.<ref name="pmid23954262">{{cite journal| author=Zeidan AM, Linhares Y, Gore SD| title=Current therapy of myelodysplastic syndromes. | journal=Blood Rev | year= 2013 | volume= 27 | issue= 5 | pages= 243-59 | pmid=23954262 | doi=10.1016/j.blre.2013.07.003 | pmc=4124605 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23954262  }} </ref>
** Adjunctive therapies include transfusion support (such as red blood cell transfusions or platelet transfusions), growth factor support (such as filgrastim), and immunosuppressive therapy, which is particularly effective in persons with PNH clones, HLA-DR15 positivity, or STAT3-mutant cytotoxic T cells.
* [[Paroxysmal nocturnal hemoglobinuria]]
** This is a clonal disorder of the hematopoietic stem cell characterized by hemolysis due to complement activation on the [[red blood cell]] membrane.<ref name="pmid26043387">{{cite journal| author=DeZern AE, Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia. | journal=Hematol Oncol Clin North Am | year= 2015 | volume= 29 | issue= 3 | pages= 479-94 | pmid=26043387 | doi=10.1016/j.hoc.2015.01.005 | pmc=4695989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26043387  }} </ref>
** It is cause of bone marrow failure.
** The genetic defect is a deficiency in glycosylphosphatidylinositol (GPI) which is encoded by the PIG-A gene.
** This protein normally serves to anchor complement regulatory and inhibitory proteins onto the [[red blood cell]] membrane.<ref name="pmid26043387">{{cite journal| author=DeZern AE, Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia. | journal=Hematol Oncol Clin North Am | year= 2015 | volume= 29 | issue= 3 | pages= 479-94 | pmid=26043387 | doi=10.1016/j.hoc.2015.01.005 | pmc=4695989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26043387  }} </ref>
** The two major regulatory proteins are CD55 (or decay accelerating factor (DAF)), which functions to degrade complement proteins C3 and C5 convertase, and CD59 (or membrane inhibitor of reactive lysis (MIRL)), which functions to prevent complement-mediated hemolysis via preventing formation of the membrane attack complex.<ref name="pmid26043387">{{cite journal| author=DeZern AE, Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia. | journal=Hematol Oncol Clin North Am | year= 2015 | volume= 29 | issue= 3 | pages= 479-94 | pmid=26043387 | doi=10.1016/j.hoc.2015.01.005 | pmc=4695989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26043387  }} </ref>
** The clinical manifestations include [[hematuria]], portal venous or hepatic venous thrombosis.
** Diagnosis is made by performing flow cytometry of peripheral blood and analyzing the expression fo CD55 and CD59 on [[red blood cell]] membranes.<ref name="pmid26043387">{{cite journal| author=DeZern AE, Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia. | journal=Hematol Oncol Clin North Am | year= 2015 | volume= 29 | issue= 3 | pages= 479-94 | pmid=26043387 | doi=10.1016/j.hoc.2015.01.005 | pmc=4695989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26043387  }} </ref>
** Treatment of this condition is eculizumab, a humanized monoclonal antibody that inhibits complement protein C5.<ref name="pmid26043387">{{cite journal| author=DeZern AE, Brodsky RA| title=Paroxysmal nocturnal hemoglobinuria: a complement-mediated hemolytic anemia. | journal=Hematol Oncol Clin North Am | year= 2015 | volume= 29 | issue= 3 | pages= 479-94 | pmid=26043387 | doi=10.1016/j.hoc.2015.01.005 | pmc=4695989 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26043387  }} </ref>
* [[Viral infection]]s
** Viruses such as [[HIV]], EBV, or CMV can cause pancytopenia.
** The diagnosis can be made by checking viral loads via PCR of peripheral blood or by checking antibody titers to the viruses.
** For example, EBV can be diagnosed by assessing for EBV DNA PCR, or by assessing for IgM or IgM to EBV antigens.
* [[Vitamin B12 deficiency]]
** This can cause [[megaloblastic anemia]].<ref name="pmid27780269">{{cite journal| author=Yadav MK, Manoli NM, Madhunapantula SV| title=Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia. | journal=PLoS One | year= 2016 | volume= 11 | issue= 10 | pages= e0164559 | pmid=27780269 | doi=10.1371/journal.pone.0164559 | pmc=5079580 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27780269  }} </ref>
* [[Copper]] deficiency
** This is a more rare cause of pancytopenia.
* [[Zinc]] deficiency
** This is a more rare cause of pancytopenia. Treatment is supplementation with zinc.


===Causes by Organ System===
===Causes by Organ System===
 
{| style="width:80%; height:100px" border="1"
{|style="width:75%; height:100px" border="1"
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
 
| style="width:75%" bgcolor="Beige" ; border="1" | No underlying causes
|style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
 
|style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | No underlying causes
 
|-
|-
 
| bgcolor="LightSteelBlue" | '''Chemical/Poisoning'''
|-bgcolor="LightSteelBlue"
| bgcolor="Beige" |[[Arsenic poisoning]], [[arsenicals]], [[benzene|benzene solvents]], [[genotoxicity|genotoxic therapy]], [[solvent|glue vapors]], [[gold]], [[mutagen|mutagen exposure]], [[mutagen|mutagen-detoxification (GSTq1-null)]], [[radium chloride]], [[toxins]], [[valproic acid|valproic acid poisoning]]
 
| '''Chemical/Poisoning'''
 
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Dental'''
| '''Dental'''
 
| bgcolor="Beige" | No underlying causes
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Dermatologic'''
| '''Dermatologic'''
 
| bgcolor="Beige" |[[Chediak-Higashi disease]], [[dyskeratosis congenita]], [[eosinophilic fasciitis]], [[melanoma]], reticular dysgenesis, [[reticulosis]], [[systemic lupus erythematosus]], [[xeroderma pigmentosum]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Drug Side Effect'''
| '''Drug Side Effect'''
 
| bgcolor="Beige" |[[Acetaminophen and Oxycodone]], [[aclarubicin]], [[albendazole]], [[alemtuzumab]], [[alkylating antineoplastic agent]], [[auranofin]], [[azathioprine]], [[aztreonam]], [[boceprevir]], [[busulfan]], [[carbamazepine]], [[carboplatin]], [[cefadroxil]], [[ceftazidime]], [[certolizumab pegol]], [[chemotherapy]], [[chloramphenicol]], [[chlorpromazine]], [[chlorpropamide]], [[cromolyn]], [[cidofovir]], [[clomipramine]], [[cyclophosphamide]], [[cytotoxic drugs]], [[dactinomycin]], [[docetaxel]], [[doxorubicin]], [[ethosuximide]], [[febuxostat]], [[flucytosine]], [[gemcitabine]], [[gemifloxacin mesylate]], [[genotoxicity|genotoxic therapy]], [[idarubicin]], [[Imipenem-Cilastatin]],[[indomethacin ]] , [[infliximab]], [[interferon beta-1a]], [[lincomycin hydrochloride]], [[minocycline hydrochloride]], [[non steroidal anti-inflammatory drugs]], [[ofatumumab]], [[omacetaxine]], [[oxaprozin]], [[oxcarbazepine]], [[penicillamine]], [[phenacemide ]] , [[phenylbutazone]], [[piperacillin]], [[pralatrexate]], [[propylthiouracil]], [[pyrimethamine]], [[rabeprazole]], [[sulfonamides ]] , [[tamoxifen]], [[temozolomide]], [[thiothixene]], [[tolazamide]], [[tolbutamide]], [[topoisomerase II|topoisomerase II interactive agents]], [[trifluoperazine]], [[trimethadione]], [[trimethoprim-sulfamethoxazole]], [[valganciclovir hydrochloride]]
|bgcolor="Beige"| [[Acetaminophen and Oxycodone]], Aclarubicin, [[Albendazole]], [[Alemtuzumab]], [[Alkylating antineoplastic agent]], Alkylators, [[Arsenicals]], [[Auranofin]], [[Azathioprine]], [[Aztreonam]], [[Boceprevir]], Busulphan, [[carbamazepine]], [[Carboplatin]], [[Cefadroxil]], [[Ceftazidime]], [[Certolizumab pegol]], [[Chlorpromazine]], [[Chloramphenicol]], [[Chlorpropamide]], [[Cidofovir]], [[Clomipramine]], [[Colchicine toxicity]], [[Cytotoxic drugs]] and [[radiation]], [[Dactinomycin]], [[Doxorubicin]], [[Ethosuximide]], [[Febuxostat]], [[Flucytosine]], [[Gold]], [[Idarubicin]], [[indomethacin ]], [[Interferon beta- 1a]], [[Lincomycin Hydrochloride]] [[Minocycline hydrochloride]], [[Non steroidal anti-inflammatory drugs]], [[Ofatumumab]], [[Omacetaxine]], [[Oxaprozin]], [[Oxcarbazepine]], [[Penicillamine]], [[phenacemide ]], Phenylbutazone, [[Piperacillin]], [[Pralatrexate]], [[ propylthiouracil ]], [[Pyrimethamine]], [[Rabeprazole]], [[ sulfonamides]], [[Tamoxifen]], [[Tolbutamide]], [[Trifluoperazine]], [[Thiothixene]], [[Valganciclovir hydrochloride]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Ear Nose Throat'''
| '''Ear Nose Throat'''
 
| bgcolor="Beige" |[[Dubowitz syndrome]], [[Jacobsen syndrome]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Endocrine'''
| '''Endocrine'''
 
| bgcolor="Beige" |[[Osteoporosis]], [[panhypopituitarism]], [[thyroid carcinoma]]
|bgcolor="Beige"|[[Thyroid carcinoma]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Environmental'''
| '''Environmental'''
 
| bgcolor="Beige" | No underlying causes
|bgcolor="Beige"|[[Tobacco]] use, Environmental/occupational (eg, benzene)
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Gastroenterologic'''
| '''Gastroenterologic'''
 
| bgcolor="Beige" |[[Banti's syndrome]], [[cirrhosis]], [[Gaucher's disease]], [[hepatosplenic T-cell lymphoma]], [[hypersplenism]], [[intrinsic factor|intrinsic factor deficiency]], [[malabsorption syndrome]], [[Plummer-Vinson syndrome]], [[portal hypertension]], [[sarcoidosis]], [[Schwachman-Diamond syndrome]], [[splenomegaly]]
|bgcolor="Beige"|[[Portal hypertension]], Intestinal [[lymphangiectasia]], [[ Hepatitis ]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Genetic'''
| '''Genetic'''
 
| bgcolor="Beige" |[[Albers-Schonberg disease]], [[ataxia telangiectasia]], [[Banti's syndrome]], [[Bloom syndrome ]] , [[cartilage-hair hypoplasia]], [[Chediak-Higashi disease]], [[Diamond-Blackfan anemia]], [[DNA repair-deficiency disorder]], [[Down syndrome]], [[Dubowitz syndrome]], [[dyskeratosis congenita]], [[familial histiocytic reticulosis]], [[monosomy|familial monosomy 7]], [[Fanconi anemia]], [[Gaucher's disease]], [[hemophagocytic lymphohistiocytosis]], [[dyskerin|Hoyeraal-Hreidarsson syndrome]], [[Jacobsen syndrome]], [[intrinsic factor|intrinsic factor deficiency]], [[neurofibromatosis 1]], [[Niemann-Pick disease]], [[osteopetrosis|osteopetrosis lethal]], [[osteopetrosis|osteopetrosis, autosomal recessive 2]], [[Pearson syndrome]], [[Schwachman-Diamond syndrome]], [[severe combined immunodeficiency]], [[TAR syndrome]], [[trisomy 8 mosaicism]], [[Wiskott-Aldrich syndrome]], [[xeroderma pigmentosum]]
|bgcolor="Beige"|[[Wiskott-Aldrich syndrome]], [[Trisomy 8]] mosaicism, Severe combined immunodeficiency, T- B+ due to JAK3 deficiency, [[Niemann-Pick disease]], [[Neurofibromatosis 1]], Mutagen-detoxification (GSTq1-null), Mutagen exposure, [[Glutathione]] synthase deficiency, Genotoxic therapy, [[Fanconi anaemia]], [[Familial]] monosomy 7, [[Down syndrome]], DNA repair deficiencies, Defect in synthesis of adenosylcobalamin, [[Chediak-Higashi disease]], [[Ataxia telangiectasia]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Hematologic'''
| '''Hematologic'''
 
| bgcolor="Beige" |[[Acute lymphoblastic leukemia]], [[acute myeloid leukemia]], [[aggressive NK-cell leukemia]], [[amegakaryocytic thrombocytopenia]], [[aplastic anemia]], [[autoimmune lymphoproliferative syndrome type 1]], [[autoimmune lymphoproliferative syndrome type 2]], [[bleeding (Excessive)]], [[bone marrow disorders|bone marrow tumor]], [[Castleman's disease]], [[chronic lymphocytic leukaemia]], [[chronic myeloid leukaemia]], [[cyclical neutropenia]], [[Diamond-Blackfan anemia]], [[familial histiocytic reticulosis]], [[myelofibrosis|familial myelofibrosis]], [[Fanconi anemia]], [[Gaucher's disease]], [[hairy cell leukemia]], [[hematopoietic stem cell transplantation]], [[hemoglobin E disease]], [[hemoglobin H disease]], [[hemoglobin SC disease]], [[hemophagocytic lymphohistiocytosis ]] , [[hepatosplenic T-cell lymphoma]], [[histiocytosis X]], [[Hodgkin's lymphoma]], [[hypersplenism]], [[myelodysplastic syndrome|hypoplastic myelodysplastic syndromes]], [[erythropoiesis|ineffective erythropoiesis]], [[lymphangiectasia|intestinal lymphangiectasia]], [[intrinsic factor|intrinsic factor deficiency]], [[iron deficiency]], [[langerhans cell histiocytosis]], [[leucoerythroblastic|leucoerythroblastic anemia]], [[leukemia]], [[lymphoma]], [[malignant histiocytosis]], [[megaloblastic anemia]], [[myelodysplastic syndrome]], [[myelofibrosis]], [[myeloma]], [[myelophthisis|myelopathic anemia]], [[non-Hodgkin lymphoma]], [[paroxysmal nocturnal hemoglobinuria]], [[Pearson syndrome]], [[pernicious anemia]], [[Plummer-Vinson syndrome]], [[acute lymphoblastic leukemia|precursor B acute lymphoblastic leukemia]], [[reticulosis]], [[Schwachman-Diamond syndrome]], [[sickle cell disease]], [[TAR syndrome]], [[t-cell large granular lymphocytic leukemia]], [[Wiskott-Aldrich syndrome]]
|bgcolor="Beige"|[[Sickle cell disease]], Reticular dysgenesis, [[Paroxysmal nocturnal haemoglobinuria]], [[Non-Hodgkin lymphoma]], Myelpathic [[anemia]],
 
[[Myeloma]], [[Myelofibrosis]], [[Myelodysplastic syndrome]], [[Megaloblastic anaemia]], [[Malignant histiocytosis]], Leucoerythroblastic [[anaemia]],
 
Large granular [[lymphocytic leukemia]], [[Langerhans cell histiocytosis]], Ineffective erythropoiesis, Hypoplastic [[myelodysplastic syndromes ]],
 
[[Hypersplenism]], [[Hodgkin lymphoma]], [[Histiocytosis X]], [[Hepatosplenic T-cell lymphoma]], [[Hemoglobin H disease]], Hematopoietic cell transplantation, [[Hairy cell leukaemia]], [[Haemoglobin SC disease]], [[Haemoglobin E disease]], [[Graft versus host disease]], Familial [[myelofibrosis]], Familial histiocytic reticulosis, [[Eosinophilic fasciitis ]], [[Cyclical neutropenia]], Congenital [[neutropenia]] (Kostmann's or Shwachman-Diamond syndrome), [[Common variable hypogammaglobulinaemia]], [[Chronic myeloid leukaemia]], [[Chronic lymphocytic leukaemia]], Bleeding (Excessive), [[Autoimmune lymphoproliferative syndrome]] type 2, [[Autoimmune lymphoproliferative syndrome]] type 1, [[Aplastic anemia]], Amegakaryocytic [[thrombocytopenia]], [[Aggressive NK-cell leukemia]], [[Acute lymphoblastic leukemia]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Iatrogenic'''
| '''Iatrogenic'''
 
| bgcolor="Beige" |[[Radiation therapy]], [[isotopes of phosphorus|radioactive p32]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Infectious Disease'''
| '''Infectious Disease'''
 
| bgcolor="Beige" |[[Babesiosis]], [[brucellosis]], [[dengue]], [[Epstein-Barr virus ]] , [[hepatitis]], [[human immunodeficiency virus ]] , [[infectious mononucleosis]], [[kala-azar]], [[Kikuchi disease]], [[lassa fever]], [[legionella pneumophila]], [[mycobacterium tuberculosis]], [[parvovirus B19 infection]], [[Q fever]], [[tuberculosis]], [[viral infections]], [[Whipple's disease]]
|bgcolor="Beige"|[[Q fever]], [[Parvovirus B19]] infection, Oklahoma tick fever, [[Mycobacterium tuberculosis]], [[Legionella pneumophila]], [[Lassa fever]], [[Human immunodeficiency virus ]], [[Epstein-Barr virus]] Seronegative, [[Dengue]], [[Brucellosis]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Musculoskeletal/Orthopedic'''
| '''Musculoskeletal/Orthopedic'''
 
| bgcolor="Beige" |[[Albers-Schonberg disease]], [[ankylosing spondylitis]], [[cartilage-hair hypoplasia]], [[Ewing's sarcoma]], [[osteoclastoma]], [[osteopetrosis|osteopetrosis lethal]], [[osteopetrosis|osteopetrosis, autosomal recessive 2]], [[osteoporosis]], [[osteosarcoma]], [[TAR syndrome]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Neurologic'''
| '''Neurologic'''
 
| bgcolor="Beige" |[[Ataxia telangiectasia]], [[Down syndrome ]] , [[neuroblastoma]], [[neurofibromatosis 1]], [[Niemann-Pick disease]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Nutritional/Metabolic'''
| '''Nutritional/Metabolic'''
 
| bgcolor="Beige" |[[Anorexia nervosa]], [[copper deficiency]], [[folate deficiency]], [[Gaucher's disease]], [[glutathione synthase|glutathione synthase deficiency]], [[iron deficiency]], [[kwashiorkor]], [[marasmus]], [[obesity]], [[vitamin B12 deficiency]], [[vitamin C deficiency]]
|bgcolor="Beige"|[[Vitamin C deficiency]], [[Vitamin B12 deficiency]], [[Marasmus]], [[Malabsorption syndrome]], [[Kwashiorkor]], [[Iron deficiency]],
 
[[Intrinsic factor]] deficiency, [[Folate deficiency]], [[Copper deficiency]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Obstetric/Gynecologic'''
| '''Obstetric/Gynecologic'''
 
| bgcolor="Beige" |[[Pregnancy]]
|bgcolor="Beige"|[[Pregnancy ]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Oncologic'''
| '''Oncologic'''
 
| bgcolor="Beige" |[[Acute lymphoblastic leukemia]], [[acute myeloid leukemia]], [[aggressive NK-cell leukemia]], [[bone marrow disorders|bone marrow tumor]], [[cancer]], [[chondrosarcoma]], [[chronic lymphocytic leukaemia]], [[chronic myeloid leukaemia]], [[tumor|epiphyseal tumors]], [[Ewing's sarcoma]], [[myelofibrosis|familial myelofibrosis]], [[germ cell tumors ]] , [[granuloma]], [[hairy cell leukemia]], [[hepatosplenic T-cell lymphoma]], [[histiocytosis X]], [[Hodgkin's lymphoma]], [[myelodysplastic syndrome|hypoplastic myelodysplastic syndromes]], [[langerhans cell histiocytosis]], [[leukemia]], [[lymphoma]], [[melanoma]], [[metastatic neoplasm]], [[myelodysplastic syndrome]], [[myelofibrosis]], [[myeloma]], [[neuroblastoma]], [[non-Hodgkin lymphoma]], [[osteoclastoma]], [[osteosarcoma]], [[ acute lymphoblastic leukemia|precursor B acute lymphoblastic leukemia]], [[prostate cancer]], [[t-cell large granular lymphocytic leukemia]], [[thymoma]], [[thyroid carcinoma]]
|bgcolor="Beige"|[[Thymoma ]], [[Prostate cancer]], Metastatic neoplasm, [[Melanoma]], [[Germ cell tumors]] (embryonal dysgenesis), [[Ewing sarcoma]], [[Chondrosarcoma]], Cancer treatment
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Ophthalmologic'''
| '''Ophthalmologic'''
 
| bgcolor="Beige" | No underlying causes
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Overdose/Toxicity'''
| '''Overdose/Toxicity'''
 
| bgcolor="Beige" |[[Colchicine toxicity]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Psychiatric'''
| '''Psychiatric'''
 
| bgcolor="Beige" |[[Anorexia nervosa]]
|bgcolor="Beige"|[[Anorexia nervosa]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Pulmonary'''
| '''Pulmonary'''
 
| bgcolor="Beige" |[[Sarcoidosis]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Renal/Electrolyte'''
| '''Renal/Electrolyte'''
 
| bgcolor="Beige" |[[Renal failure, chronic]], [[systemic lupus erythematosus]]
|bgcolor="Beige"|[[Renal failure, chronic]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Rheumatology/Immunology/Allergy'''
| '''Rheumatology/Immunology/Allergy'''
 
| bgcolor="Beige" |[[Ankylosing spondylitis]], [[auto-immune disorders]], [[autoimmune lymphoproliferative syndrome type 1]], [[autoimmune lymphoproliferative syndrome type 2]], [[Castleman's disease]], [[common variable immunodeficiency|common variable hypogammaglobulinemia]], [[common variable immune deficiency]], [[eosinophilic fasciitis ]] , [[Felty's syndrome]], [[graft versus host disease]], [[histiocytosis X]], [[langerhans cell histiocytosis]], [[rheumatoid disease]], [[sarcoidosis]], [[severe combined immunodeficiency]], [[systemic lupus erythematosus]], [[Wiskott-Aldrich syndrome]]
|bgcolor="Beige"|[[Systemic lupus erythematosus]], [[Rheumatoid disease]], [[Osteopetrosis]] autosomal recessive 2, [[Osteopetrosis]] lethal
 
Osteoclastoma, [[Ankylosing spondylitis]]
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Sexual'''
| '''Sexual'''
 
| bgcolor="Beige" | No underlying causes
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Trauma'''
| '''Trauma'''
 
| bgcolor="Beige" | No underlying causes
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Urologic'''
| '''Urologic'''
 
| bgcolor="Beige" |[[Prostate cancer]]
|bgcolor="Beige"| No underlying causes
 
|-
|-
 
|- bgcolor="LightSteelBlue"
|-bgcolor="LightSteelBlue"
 
| '''Miscellaneous'''
| '''Miscellaneous'''
 
| bgcolor="Beige" |[[Idiopathic]], [[isotopes of phosphorus|radioactive p32]], [[tobacco use]]
|bgcolor="Beige"|Topoisomerase II interactive agents, [[Plummer-Vinson syndrome]], [[Obesity]], [[Idiopathic ]], Glue vapors, Dyskeratosis congenita Shwachman-Diamond syndrome,  Diamond-Blackfan [[anemia]], [[Castleman disease]], [[Bloom's syndrome ]]
 
|-
|-
|}
|}


===Causes in Alphabetical Order===
===Causes in Alphabetical Order===
 
{{columns-list|
{{col-begin|width=84%}}
*[[Acetaminophen and Oxycodone]]
 
*[[Aclarubicin]]
{{col-break|width=33%}}
*[[Acute lymphoblastic leukemia]] <ref name="pmid21941136">{{cite journal| author=Shah NR, Landi DB, Kreissman SG, Kulbachi E, Moran C| title=Presentation and outcomes for children with bone marrow necrosis and acute lymphoblastic leukemia: a literature review. | journal=J Pediatr Hematol Oncol | year= 2011 | volume= 33 | issue= 7 | pages= e316-9 | pmid=21941136 | doi=10.1097/MPH.0b013e318223fe9b | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21941136  }} </ref>
 
*[[Acute myeloid leukemia]] <ref name="pmid24353701">{{cite journal| author=Das Makheja K, Kumar Maheshwari B, Arain S, Kumar S, Kumari S| title=The common causes leading to pancytopenia in patients presenting to tertiary care hospital. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 5 | pages= 1108-11 | pmid=24353701 | doi= | pmc=PMC3858928 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353701  }} </ref>
*Aclarubicin
*[[Aggressive NK-cell leukemia]] <ref name="pmid15953954">{{cite journal| author=Guerrero A M, Lira V P, Bertin C P, Galleguillos V M, Ocqueteau T M| title=[Natural killer cell leukemia. Case report]. | journal=Rev Med Chil | year= 2005 | volume= 133 | issue= 4 | pages= 457-60 | pmid=15953954 | doi=/S0034-98872005000400010 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15953954  }} </ref>
 
*[[Acute lymphoblastic leukemia]]
 
*[[Aggressive NK-cell leukemia]]
 
*[[Albendazole]]
*[[Albendazole]]
 
*[[Albers-Schonberg disease]]
*[[Alemtuzumab]]
*[[Alemtuzumab]]
*[[Alkylating antineoplastic agent]]
*[[Alkylating antineoplastic agent]]
 
*[[Amegakaryocytic thrombocytopenia ]]  
*Alkylators
 
*Amegakaryocytic [[thrombocytopenia ]]
 
*[[Ankylosing spondylitis]]
*[[Ankylosing spondylitis]]
 
*[[Anorexia nervosa]] <ref name="pmid15139557">{{cite journal| author=Vande Zande VL, Mazza JJ, Yale SH| title=Hematologic and metabolic abnormalities in a patient with anorexia nervosa. | journal=WMJ | year= 2004 | volume= 103 | issue= 2 | pages= 38-40 | pmid=15139557 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15139557  }} </ref>
*[[Anorexia nervosa]]
 
*[[Aplastic anemia]]
*[[Aplastic anemia]]
 
*[[Arsenic poisoning]]
*[[Arsenicals]]
*[[Arsenicals]]  
 
*[[Ataxia telangiectasia]]
*[[Ataxia telangiectasia]]
*[[Auranofin]]
*[[Auranofin]]
*[[Autoimmune lymphoproliferative syndrome type 1]]
*[[Autoimmune lymphoproliferative syndrome type 1]]
 
*[[Autoimmune lymphoproliferative syndrome type 2]]  
*[[Autoimmune lymphoproliferative syndrome type 2]]
*[[Azathioprine]] <ref name="pmid7458518">{{cite journal| author=Bacon BR, Treuhaft WH, Goodman AM| title=Azathioprine-induced pancytopenia. Occurrence in two patients with connective-tissue diseases. | journal=Arch Intern Med | year= 1981 | volume= 141 | issue= 2 | pages= 223-6 | pmid=7458518 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7458518  }} </ref>
 
*[[Aztreonam]]  
*[[Azathioprine]]
*[[Babesiosis]] <ref name="pmid23432953">{{cite journal| author=Poisnel E, Ebbo M, Berda-Haddad Y, Faucher B, Bernit E, Carcy B et al.| title=Babesia microti: an unusual travel-related disease. | journal=BMC Infect Dis | year= 2013 | volume= 13 | issue=  | pages= 99 | pmid=23432953 | doi=10.1186/1471-2334-13-99 | pmc=PMC3598249 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23432953  }} </ref>
 
*[[Banti's syndrome]]
*[[Aztreonam]]
*[[benzene|Benzene solvents]] <ref name="pmid6578748">{{cite journal| author=Braier L| title=An hypothesis for the induction of leukemia by benzene. | journal=Arch Toxicol Suppl | year= 1983 | volume= 6 | issue=  | pages= 42-6 | pmid=6578748 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6578748  }} </ref>
 
*[[isotopes of phosphorus|Radioactive p32]]
*Benzene Solvents
 
*Beta-emitters (eg, radioactive P-32)
 
*[[Bleeding (Excessive)]]
*[[Bleeding (Excessive)]]
 
*[[Bloom syndrome ]]
*[[Bloom's syndrome ]]
 
*[[Boceprevir]]
*[[Boceprevir]]
 
*[[bone marrow disorders|Bone marrow tumor]]
*[[Brucellosis]]
*[[Brucellosis]] <ref name="pmid24820461">{{cite journal| author=Guler S, Kokoglu OF, Ucmak H, Gul M, Ozden S, Ozkan F| title=Human brucellosis in Turkey: different clinical presentations. | journal=J Infect Dev Ctries | year= 2014 | volume= 8 | issue= 5 | pages= 581-8 | pmid=24820461 | doi=10.3855/jidc.3510 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24820461  }} </ref>
 
*[[Busulfan]]
*Busulphan
*[[Cancer]]
 
*[[Carbamazepine]]
*Cancer treatment
 
*[[carbamazepine]]
 
*[[Carboplatin]]
*[[Carboplatin]]
 
*[[Cartilage-hair hypoplasia]]
*[[Castleman disease]]
*[[Castleman's disease]]
 
*[[Cefadroxil]]
*[[Cefadroxil]]
 
*[[Ceftazidime]]  
*[[Ceftazidime]]
*[[Certolizumab pegol]]
 
*[[Chediak-Higashi disease]]  
*[[Chediak-Higashi disease]]
*[[Chemotherapy]]
 
*[[Chloramphenicol]]  
*[[Chloramphenicol]]
*[[Chlorpromazine]]
 
*[[Chlorpropamide]]
*[[Chlorpropamide]]  
*[[Chondrosarcoma]]  
 
*[[Chondrosarcoma]]
 
*[[Chronic lymphocytic leukaemia]]
*[[Chronic lymphocytic leukaemia]]
 
*[[Chronic myeloid leukaemia]]  
*[[Chronic myeloid leukaemia]]
 
*[[Cidofovir]]
*[[Cidofovir]]
 
*[[Cirrhosis]]
*[[Clomipramine]]
*[[Clomipramine]]
*[[Colchicine toxicity]]
*[[Colchicine toxicity]]
 
*[[common variable immunodeficiency|Common variable hypogammaglobulinemia]]
*[[Common variable hypogammaglobulinaemia]]
*[[Common variable immune deficiency]] <ref name="pmid24433602">{{cite journal| author=Bajaj P, Clement J, Bayerl MG, Kalra N, Craig TJ, Ishmael FT| title=High-grade fever and pancytopenia in an adult patient with common variable immune deficiency. | journal=Allergy Asthma Proc | year= 2014 | volume= 35 | issue= 1 | pages= 78-82 | pmid=24433602 | doi=10.2500/aap.2014.35.3704 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24433602  }} </ref>
 
*Congenital [[neutropenia]] (Kostmann's or Shwachman-Diamond syndrome)
 
*[[Copper deficiency]]
*[[Copper deficiency]]
*[[Cyclical neutropenia]]
*[[Cyclical neutropenia]]
 
*[[Cyclophosphamide]]
*[[Cytotoxic]] drugs and [[radiation ]]
*[[Cytotoxic drugs]]
 
*[[Dactinomycin]]
*Defect in synthesis of adenosylcobalamin
 
*[[Dengue]]
*[[Dengue]]
*[[Diamond-Blackfan anemia]]
*[[Diamond-Blackfan anemia]]
 
*[[DNA repair-deficiency disorder]]
*DNA repair deficiencies
*[[Docetaxel]]
 
*[[Down syndrome ]]  
*[[Down syndrome]] (trisomy 21)
 
*[[Doxorubicin]]
*[[Doxorubicin]]
 
*[[Dubowitz syndrome]]
*Dyskeratosis congenita Shwachman-Diamond syndrome
*[[Dyskeratosis congenita]] <ref name="pmid19615640">{{cite journal| author=Abdel-Karim A, Frezzini C, Viggor S, Davidson LE, Thornhill MH, Yeoman CM| title=Dyskeratosis congenita: a case report. | journal=Oral Surg Oral Med Oral Pathol Oral Radiol Endod | year= 2009 | volume= 108 | issue= 2 | pages= e20-4 | pmid=19615640 | doi=10.1016/j.tripleo.2009.03.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19615640  }} </ref>
 
{{col-break|width=33%}}
 
*Environmental/occupational (eg, benzene)
 
*[[Eosinophilic fasciitis ]]
*[[Eosinophilic fasciitis ]]
 
*[[tumors|Epiphyseal tumors]]
*[[Epstein-Barr virus]] Seronegative
*[[Epstein-Barr virus]] <ref name="pmid24228130">{{cite journal| author=Zhang X, Wang Z, Wang L, Yao H| title=An adult case of systemic Epstein-Barr virus-positive T/natural killer-cell lymphoproliferative disorder with good outcome. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 11 | pages= 2620-4 | pmid=24228130 | doi= | pmc=PMC3816837 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24228130  }} </ref>
 
*[[Ethosuximide]]
*[[Ewing sarcoma]]
*[[Ewing's sarcoma]]
 
*[[Familial histiocytic reticulosis]]
*[[Familial]] histiocytic reticulosis
*[[monosomy|Familial monosomy 7]]
 
*[[myelofibrosis|Familial myelofibrosis]]
*[[Familial]] monosomy 7
*[[Fanconi anemia]]
 
*[[Febuxostat]]
*[[Familial]] [[myelofibrosis]]
*[[Felty's syndrome]]  
 
*[[Fanconi anaemia]]
 
*[[Flucytosine]]
*[[Flucytosine]]
 
*[[Folate deficiency]] <ref name="pmid21659050">{{cite journal| author=Roche C, Roche NC, Thefenne H, Saidi R, De Pina JJ, Molinier S et al.| title=[Pancytopenia and folate deficiency: a case report]. | journal=Ann Biol Clin (Paris) | year= 2011 | volume= 69 | issue= 3 | pages= 331-5 | pmid=21659050 | doi=10.1684/abc.2011.0584 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21659050  }} </ref>
*[[Folate deficiency]]
*[[Gaucher's disease]]
 
*[[Gemcitabine]]  
*Genotoxic therapy  
*[[Gemifloxacin mesylate]]
 
*[[genotoxicity|Genotoxic therapy]]
*[[Germ cell]] tumors (embryonal dysgenesis)
*[[Germ cell tumors ]] <ref name="pmid24005437">{{cite journal| author=Suyama T, Obara N, Kawai K, Yamada K, Kusakabe M, Kurita N et al.| title=[Acute myeloid leukemia possibly originating from the same clone of testicular germ cell tumor]. | journal=Rinsho Ketsueki | year= 2013 | volume= 54 | issue= 8 | pages= 764-8 | pmid=24005437 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24005437  }} </ref>
 
*[[solvent|Glue vapors]]
*Glue vapors  
*[[glutathione synthase|Glutathione synthase deficiency]]
 
*[[Gold]]
*Glutathione synthase deficiency
*[[Graft versus host disease]] <ref name="pmid17655584">{{cite journal| author=Agbaht K, Altintas ND, Topeli A, Gokoz O, Ozcebe O| title=Transfusion-associated graft-versus-host disease in immunocompetent patients: case series and review of the literature. | journal=Transfusion | year= 2007 | volume= 47 | issue= 8 | pages= 1405-11 | pmid=17655584 | doi=10.1111/j.1537-2995.2007.01282.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17655584  }} </ref>
 
*[[Granuloma]]
*[[Gold ]]
*[[Hairy cell leukemia]] <ref name="pmid22351675">{{cite journal| author=Fino P, Fioramonti P, Onesti MG, Passaretti D, Scuderi N| title=Skin metastasis in patient with hairy cell leukemia: case report and review of literature. | journal=In Vivo | year= 2012 | volume= 26 | issue= 2 | pages= 311-4 | pmid=22351675 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22351675  }} </ref>
 
*[[Hematopoietic stem cell transplantation]]
*[[Graft versus host disease]]
*[[Hemoglobin E disease]]
 
*[[Haemoglobin E disease]]
 
*[[Haemoglobin SC disease]]
 
*[[Hairy cell leukaemia]]
 
*Hematopoietic cell transplantation
 
*[[Hemoglobin H disease]]
*[[Hemoglobin H disease]]
 
*[[Hemoglobin SC disease]]
*[[ Hepatitis ]]
*[[Hemophagocytic lymphohistiocytosis]] <ref name="pmid22193223">{{cite journal| author=Giri PP, Pal P, Ghosh A, Sinha R| title=Infection-associated haemophagocytic lymphohistiocytosis: a case series using steroids only protocol for management. | journal=Rheumatol Int | year= 2013 | volume= 33 | issue= 5 | pages= 1363-6 | pmid=22193223 | doi=10.1007/s00296-011-2291-2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22193223  }} </ref>
 
*[[Hepatitis]]
*[[Hepatosplenic T-cell lymphoma]]
*[[Hepatosplenic T-cell lymphoma]]
*[[Histiocytosis X]]
*[[Histiocytosis X]]
 
*[[Hodgkin's lymphoma]]
*[[Hodgkin lymphoma]]
*[[dyskerin|Hoyeraal-Hreidarsson syndrome]]
 
*[[Human immunodeficiency virus ]]
*[[Human immunodeficiency virus ]]
 
*[[Hypersplenism]] <ref name="pmid24238033">{{cite journal| author=Jain A, Naniwadekar M| title=An etiological reappraisal of pancytopenia - largest series reported to date from a single tertiary care teaching hospital. | journal=BMC Hematol | year= 2013 | volume= 13 | issue= 1 | pages= 10 | pmid=24238033 | doi=10.1186/2052-1839-13-10 | pmc=PMC4177001 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24238033  }} </ref>
*[[Hypersplenism]]
*[[myelodysplastic syndrome|Hypoplastic myelodysplastic syndromes]] <ref name="pmid17701956">{{cite journal| author=Konoplev S, Medeiros LJ, Lennon PA, Prajapati S, Kanungo A, Lin P| title=Therapy may unmask hypoplastic myelodysplastic syndrome that mimics aplastic anemia. | journal=Cancer | year= 2007 | volume= 110 | issue= 7 | pages= 1520-6 | pmid=17701956 | doi=10.1002/cncr.22935 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17701956  }} </ref>
 
*Hypoplastic [[myelodysplastic syndromes ]]
 
*[[Idarubicin]]
*[[Idarubicin]]
 
*[[Idiopathic]]
*[[Idiopathic ]]
*[[Auto-immune disorders]]
 
*[[Indomethacin ]]
*[[indomethacin ]]
*[[erythropoiesis|Ineffective erythropoiesis]]
 
*[[Infectious mononucleosis]]
*Ineffective [[erythropoiesis]]
 
*Intestinal [[lymphangiectasia]]
 
*[[Infliximab]]
*[[Infliximab]]
 
*[[Interferon beta-1a]]
*Intrinsic factor deficiency
*[[lymphangiectasia|Intestinal lymphangiectasia]]
 
*[[intrinsic factor|Intrinsic factor deficiency]]
*[[Iron deficiency]]
*[[Iron deficiency]]
 
*[[Jacobsen syndrome]] <ref name="pmid19267933">{{cite journal| author=Mattina T, Perrotta CS, Grossfeld P| title=Jacobsen syndrome. | journal=Orphanet J Rare Dis | year= 2009 | volume= 4 | issue=  | pages= 9 | pmid=19267933 | doi=10.1186/1750-1172-4-9 | pmc=PMC2670819 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19267933  }} </ref>
*[[Kala-azar]] <ref name="pmid8373548">{{cite journal| author=Trejo-Pérez JA, Miranda-Novales MG, Solórzano-Santos F, Cabrera-Muñoz L, Díaz-Ponce H| title=[Kala-azar in Mexico: report of 2 cases]. | journal=Bol Med Hosp Infant Mex | year= 1993 | volume= 50 | issue= 9 | pages= 662-5 | pmid=8373548 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8373548  }} </ref>
*[[Kikuchi disease]]
*[[Kwashiorkor]]
*[[Kwashiorkor]]
 
*[[Langerhans cell histiocytosis]]  
*[[Langerhans cell histiocytosis]]
 
*Large granular lymphocytic [[leukemia]]
 
*[[Lassa fever]]
*[[Lassa fever]]
*[[Legionella pneumophila]]
*[[Legionella pneumophila]]
 
*[[leucoerythroblastic|Leucoerythroblastic anemia]]
*Leucoerythroblastic [[anaemia]]
*[[Leukemia]]
 
*[[Lincomycin hydrochloride]]
*[[Lymphoma]]
*[[Malabsorption syndrome]]
*[[Malabsorption syndrome]]
*[[Malignant histiocytosis]]
*[[Malignant histiocytosis]]
*[[Marasmus]]
*[[Marasmus]]
 
*[[Megaloblastic anemia]] <ref name="pmid24669609">{{cite journal| author=Khattak MB, Ismail M, Marwat ZI, Khan F| title=Frequency and characterisation of pancytopenia in megaloblastic anaemia. | journal=J Ayub Med Coll Abbottabad | year= 2012 | volume= 24 | issue= 3-4 | pages= 53-5 | pmid=24669609 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24669609  }} </ref>
*[[Megaloblastic anaemia]]
 
*[[Melanoma]]
*[[Melanoma]]
 
*[[Metastatic neoplasm]]
*Metastatic neoplasm
*[[Minocycline hydrochloride]]
 
*[[mutagen|Mutagen exposure]]
{{col-break|width=33%}}
*[[mutagen|Mutagen-detoxification (GSTq1-null)]]
 
*Mutagen exposure  
 
*Mutagen-detoxification (GSTq1-null)
 
*[[Mycobacterium tuberculosis]]
*[[Mycobacterium tuberculosis]]
 
*[[Myelodysplastic syndrome]] <ref name="pmid24300826">{{cite journal| author=Germing U, Kobbe G, Haas R, Gattermann N| title=Myelodysplastic syndromes: diagnosis, prognosis, and treatment. | journal=Dtsch Arztebl Int | year= 2013 | volume= 110 | issue= 46 | pages= 783-90 | pmid=24300826 | doi=10.3238/arztebl.2013.0783 | pmc=PMC3855821 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24300826  }} </ref>
*[[Myelodysplastic syndrome]]
 
*[[Myelofibrosis]]
*[[Myelofibrosis]]
*[[Myeloma]]
*[[Myeloma]]
 
*[[myelophthisis|Myelopathic anemia]]
*Myelpathic [[anemia]]
*[[Neuroblastoma]]
 
*[[Neurofibromatosis 1]]
*[[Neurofibromatosis 1]]
*[[Niemann-Pick disease]]
*[[Niemann-Pick disease]]
*[[Non steroidal anti-inflammatory drugs ]]
*[[Non steroidal anti-inflammatory drugs ]]
*[[Non-Hodgkin lymphoma]]
*[[Non-Hodgkin lymphoma]]
*[[Obesity]]
*[[Obesity]]
 
*[[Ofatumumab]]
*Oklahoma [[tick fever]]
*[[Omacetaxine]]
 
*[[Osteoclastoma]]
*Osteoclastoma
*[[osteopetrosis|Osteopetrosis lethal]]
 
*[[osteopetrosis|Osteopetrosis, autosomal recessive 2]]
*[[Osteopetrosis]] lethal
*[[Osteoporosis]]
 
*[[Osteopetrosis]], autosomal recessive 2
 
*[[Osteosarcoma]]
*[[Osteosarcoma]]
*[[Oxaprozin]]
*[[Oxaprozin]]
 
*[[Oxcarbazepine]]
*[[Paroxysmal nocturnal haemoglobinuria]]
*[[Panhypopituitarism]]
 
*[[Paroxysmal nocturnal hemoglobinuria]] <ref name="pmid1879240">{{cite journal| author=Zhang ZN, Liu EK| title=[Clinical features of paroxysmal nocturnal hemoglobinuria (PNH) in China as compared with those in United Kingdom]. | journal=Zhonghua Nei Ke Za Zhi | year= 1991 | volume= 30 | issue= 5 | pages= 276-9, 317 | pmid=1879240 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1879240  }} </ref>
*[[Parvovirus B19 infection]]
*[[Parvovirus B19 infection]] <ref name="pmid23730023">{{cite journal| author=Rajput R, Sehgal A, Jain D, Sen R, Gupta A| title=Acute parvovirus b19 infection leading to severe aplastic anemia in a previously healthy adult female. | journal=Indian J Hematol Blood Transfus | year= 2012 | volume= 28 | issue= 2 | pages= 123-6 | pmid=23730023 | doi=10.1007/s12288-011-0112-0 | pmc=PMC3332267 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23730023  }} </ref>
 
*[[Pearson syndrome]]
*[[phenacemide ]]
*[[Penicillamine]] <ref name="pmid228408">{{cite journal| author=Franck JL, Bouteiller G, Gayrard M, Arlet J| title=[D-penicillamine in rheumatoid arthritis : hematological incidents and accidents (author's transl)]. | journal=Sem Hop | year= 1979 | volume= 55 | issue= 27-30 | pages= 1325-7 | pmid=228408 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=228408  }} </ref>
 
*[[Pernicious anemia]] <ref name="pmid23400269">{{cite journal| author=Song IC, Lee HJ, Kim HJ, Bae SB, Lee KT, Yang YJ et al.| title=A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population. | journal=J Korean Med Sci | year= 2013 | volume= 28 | issue= 2 | pages= 200-4 | pmid=23400269 | doi=10.3346/jkms.2013.28.2.200 | pmc=PMC3565130 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23400269  }} </ref>
*[[phenylbutazone ]]
*[[Phenacemide ]]
 
*[[Phenylbutazone]]
*[[Piperacillin]]
*[[Plummer-Vinson syndrome]]
*[[Plummer-Vinson syndrome]]
 
*[[Portal hypertension]]  
*[[Portal hypertension]]
*[[Pralatrexate]]
 
*[[Precursor B acute lymphoblastic leukemia/lymphoma]]
*[[Pregnancy ]]
*[[Pregnancy ]]
 
*[[Propylthiouracil]]
*[[Prostate cancer]]
*[[Prostate cancer]]
*[[Pyrimethamine]]
*[[Q fever]]
*[[Rabeprazole]]
*[[Radiation therapy]] <ref name="pmid21930984">{{cite journal| author=Birkeland AC, Auerbach AD, Sanborn E, Parashar B, Kuhel WI, Chandrasekharappa SC et al.| title=Postoperative clinical radiosensitivity in patients with fanconi anemia and head and neck squamous cell carcinoma. | journal=Arch Otolaryngol Head Neck Surg | year= 2011 | volume= 137 | issue= 9 | pages= 930-4 | pmid=21930984 | doi=10.1001/archoto.2011.154 | pmc=PMC3343719 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21930984  }} </ref>
*[[Radium chloride]]
*[[Renal failure, chronic]]
*Reticular dysgenesis
*[[Reticulosis]]
*[[Rheumatoid disease]]
*[[Sarcoidosis]] <ref name="pmid11481582">{{cite journal| author=Bauer H| title=[Fatal outcome of a multisystemic sarcoidosis in a 54-year-old patient]. | journal=Pneumologie | year= 2001 | volume= 55 | issue= 7 | pages= 343-6 | pmid=11481582 | doi=10.1055/s-2001-15617 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11481582  }} </ref>
*[[Schwachman-Diamond syndrome]]
*[[Severe combined immunodeficiency]] <ref name="pmid17481714">{{cite journal| author=Palmer K, Green TD, Roberts JL, Sajaroff E, Cooney M, Parrott R et al.| title=Unusual clinical and immunologic manifestations of transplacentally acquired maternal T cells in severe combined immunodeficiency. | journal=J Allergy Clin Immunol | year= 2007 | volume= 120 | issue= 2 | pages= 423-8 | pmid=17481714 | doi=10.1016/j.jaci.2007.02.047 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17481714  }} </ref>
*[[Sickle cell disease]]
*[[Splenomegaly]]
*[[Sulfonamides ]]
*[[Systemic lupus erythematosus]] <ref name="pmid20329445">{{cite journal| author=Sarkar RN, Banerjee S, Dey S, Saha A, Bhattacharjee P, Banerjee TK et al.| title=Haematological presentation of systemic lupus erythematosus. | journal=J Assoc Physicians India | year= 2009 | volume= 57 | issue=  | pages= 767-8 | pmid=20329445 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20329445  }} </ref>
*[[Tamoxifen]]
*[[TAR syndrome]]
*[[T-cell large granular lymphocytic leukemia]] <ref name="pmid21337493">{{cite journal| author=Song S| title=A case report: Concurrent chronic myelomonocytic leukemia and T-cell large granular lymphocytic leukemia-type clonal proliferation as detected by multiparametric flow cytometry. | journal=Cytometry B Clin Cytom | year= 2011 | volume= 80 | issue= 2 | pages= 126-9 | pmid=21337493 | doi=10.1002/cyto.b.20565 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21337493  }} </ref>
*[[Temozolomide]] <ref name="pmid21614470">{{cite journal| author=Villano JL, Letarte N, Yu JM, Abdur S, Bressler LR| title=Hematologic adverse events associated with temozolomide. | journal=Cancer Chemother Pharmacol | year= 2012 | volume= 69 | issue= 1 | pages= 107-13 | pmid=21614470 | doi=10.1007/s00280-011-1679-8 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21614470  }} </ref>
*[[Thiothixene]]
*[[Thymoma]]
*[[Thyroid carcinoma]]
*[[Tobacco use]]
*[[Tolazamide]]
*[[Tolbutamide]]
*[[type II topoisomerase|Topoisomerase II interactive agents]]
*[[Toxins]]
*[[Trifluoperazine]]
*[[Trimethadione]]
*[[Trimethoprim-sulfamethoxazole]]
*[[Trisomy 8 mosaicism]]
*[[Tuberculosis]] <ref name="pmid20359619">{{cite journal| author=Le Hô H, Barbarot N, Desrues B| title=[Pancytopenia in disseminated tuberculosis: Think of macrophage activation syndrome]. | journal=Rev Mal Respir | year= 2010 | volume= 27 | issue= 3 | pages= 257-60 | pmid=20359619 | doi=10.1016/j.rmr.2010.02.005 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20359619  }} </ref>
*[[Valganciclovir hydrochloride]]
*[[valproic acid|Valproic acid poisoning]] <ref name="pmid22010461">{{cite journal| author=Klimaszyk D, Łukasik-Głebocka M| title=[Pancytopenia in the course of acute valproic acid poisoning--case report]. | journal=Przegl Lek | year= 2011 | volume= 68 | issue= 8 | pages= 539-42 | pmid=22010461 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22010461  }} </ref><ref name="pmid22797722">{{cite journal| author=Eom TH, Lee HS, Jang PS, Kim YH| title=Valproate-induced panhypogammaglobulinemia. | journal=Neurol Sci | year= 2013 | volume= 34 | issue= 6 | pages= 1003-4 | pmid=22797722 | doi=10.1007/s10072-012-1153-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22797722  }} </ref>
*[[Viral infections]]
*[[Vitamin B12 deficiency]]
*[[Vitamin C deficiency]]
*[[Whipple's disease]] <ref name="pmid24765256">{{cite journal| author=Tun NT, Shukla S, Krishnakurup J, Pappachen B, Krishnamurthy M, Salib H| title=An unusual cause of pancytopenia: Whipple's disease. | journal=J Community Hosp Intern Med Perspect | year= 2014 | volume= 4 | issue=  | pages=  | pmid=24765256 | doi=10.3402/jchimp.v4.23482 | pmc=PMC3992356 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24765256  }} </ref>
*[[Wiskott-Aldrich syndrome]]
*[[Xeroderma pigmentosum]]
}}


*[[Propylthiouracil]]
===Causes by Pathophysiology===
====Bone Marrow Failure====
* Insufficient production ([[aplastic anemia]])
* Inability of cells or mature ([[myelodysplasia]])
* Replacement of normal bone marrow with [[fibrosis]] ([[myelofibrosis]])


*[[Pyrimethamine]]
====Peripheral Sequestration/Destruction====
* [[Splenomegaly]]
* [[Hypersplenism]]


*[[Q fever]]
===Causes by Mode of Inheritance===
This is not applicable since there is no specific mode of inheritance for pancytopenia.


*[[Renal failure, chronic]]
====Congenital====
*[[Cartilage hair hypoplasia]]:
**This is a bone marrow failure condition caused by ribosomal protein mutations.<ref name="pmid24237972">{{cite journal| author=Chirnomas SD, Kupfer GM| title=The inherited bone marrow failure syndromes. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1291-310 | pmid=24237972 | doi=10.1016/j.pcl.2013.09.007 | pmc=3875142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237972  }} </ref>
**Clinical manifestations include cartilage and hair loss.
*[[Diamond-Blackfan syndrome]]:
**This is a rare condition affecting 5-7 persons per million and is characterized by a [[macrocytic anemia]] and less than 5% erythroid precursors including reticulocytes.<ref name="pmid20655265">{{cite journal| author=Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T| title=Diamond-Blackfan anemia, ribosome and erythropoiesis. | journal=Transfus Clin Biol | year= 2010 | volume= 17 | issue= 3 | pages= 112-9 | pmid=20655265 | doi=10.1016/j.tracli.2010.06.001 | pmc=3699172 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20655265  }} </ref>
**It is the most common inherited erythrocyte failure syndrome, and it is inherited in an autosomal dominant pattern.<ref name="pmid24237972">{{cite journal| author=Chirnomas SD, Kupfer GM| title=The inherited bone marrow failure syndromes. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1291-310 | pmid=24237972 | doi=10.1016/j.pcl.2013.09.007 | pmc=3875142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237972  }} </ref>
**This condition is caused by mutations in ribosomal protein genes such as RPS19.
**Though neutropenia and thrombocytopenia do not usually occur, moderate white blood cell and platelet count reductions have been described in some cases.<ref name="pmid20655265">{{cite journal| author=Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T| title=Diamond-Blackfan anemia, ribosome and erythropoiesis. | journal=Transfus Clin Biol | year= 2010 | volume= 17 | issue= 3 | pages= 112-9 | pmid=20655265 | doi=10.1016/j.tracli.2010.06.001 | pmc=3699172 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20655265  }} </ref>
**Fetal hemoglobin is typically increased in an effect to enhance delivery of oxygen to tissues in the setting of low hemoglobin.<ref name="pmid20655265">{{cite journal| author=Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T| title=Diamond-Blackfan anemia, ribosome and erythropoiesis. | journal=Transfus Clin Biol | year= 2010 | volume= 17 | issue= 3 | pages= 112-9 | pmid=20655265 | doi=10.1016/j.tracli.2010.06.001 | pmc=3699172 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20655265  }} </ref>
**Clinical manifestations usually include short statute, ocular abnormalities, skeletal abnormalities.
**It is the most common inherited erythrocyte failure syndrome.<ref name="pmid24237972">{{cite journal| author=Chirnomas SD, Kupfer GM| title=The inherited bone marrow failure syndromes. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1291-310 | pmid=24237972 | doi=10.1016/j.pcl.2013.09.007 | pmc=3875142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237972  }} </ref>
**The only curative therapy is bone marrow transplantation.
*[[Dubowitz syndrome]]
**This is a rare autosomal recessive disorder characterized by increased cancer susceptibility.<ref name="pmid23372718">{{cite journal| author=Yue J, Lu H, Lan S, Liu J, Stein MN, Haffty BG et al.| title=Identification of the DNA repair defects in a case of Dubowitz syndrome. | journal=PLoS One | year= 2013 | volume= 8 | issue= 1 | pages= e54389 | pmid=23372718 | doi=10.1371/journal.pone.0054389 | pmc=3556036 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23372718  }} </ref>
**The exact genetic abnormality and etiology is yet to be identified.
**Patients have DNA that is very sensitive to ionizing radiation and a few chemotherapy agents like anthracyclines and bleomycin.<ref name="pmid23372718">{{cite journal| author=Yue J, Lu H, Lan S, Liu J, Stein MN, Haffty BG et al.| title=Identification of the DNA repair defects in a case of Dubowitz syndrome. | journal=PLoS One | year= 2013 | volume= 8 | issue= 1 | pages= e54389 | pmid=23372718 | doi=10.1371/journal.pone.0054389 | pmc=3556036 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23372718  }} </ref>
**There is some clinical overlap with Fanconi anemia.<ref name="pmid23372718">{{cite journal| author=Yue J, Lu H, Lan S, Liu J, Stein MN, Haffty BG et al.| title=Identification of the DNA repair defects in a case of Dubowitz syndrome. | journal=PLoS One | year= 2013 | volume= 8 | issue= 1 | pages= e54389 | pmid=23372718 | doi=10.1371/journal.pone.0054389 | pmc=3556036 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23372718  }} </ref>
**Patients can develop bone marrow failure and cytopenias.
*[[Dyskeratosis congenita]]
**This is a rare condition caused by short telomeres, which normally function to maintain the length and integrity of DNA.<ref name="pmid21745483">{{cite journal| author=Nelson ND, Bertuch AA| title=Dyskeratosis congenita as a disorder of telomere maintenance. | journal=Mutat Res | year= 2012 | volume= 730 | issue= 1-2 | pages= 43-51 | pmid=21745483 | doi=10.1016/j.mrfmmm.2011.06.008 | pmc=3208805 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21745483  }} </ref>
**It is characterized by skin abnormalities, nail abnormalities, and [[leukoplakia]].
**The genes implicated include DKC1 (dyskerin), TERT, and TERC.
**Other genes implicated in this condition encode ribonucleoprotein enzymes.
**By age 30, approximately 80% of patients with this condition will develop bone marrow failure.<ref name="pmid21745483">{{cite journal| author=Nelson ND, Bertuch AA| title=Dyskeratosis congenita as a disorder of telomere maintenance. | journal=Mutat Res | year= 2012 | volume= 730 | issue= 1-2 | pages= 43-51 | pmid=21745483 | doi=10.1016/j.mrfmmm.2011.06.008 | pmc=3208805 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21745483  }} </ref>
*[[Fanconi's anemia]]
**This is a condition characterized by erythrocyte hypoproduction due to genomic instability and increased susceptibility to DNA damaging agents.<ref name="pmid24237972">{{cite journal| author=Chirnomas SD, Kupfer GM| title=The inherited bone marrow failure syndromes. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1291-310 | pmid=24237972 | doi=10.1016/j.pcl.2013.09.007 | pmc=3875142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237972  }} </ref> <ref name="pmid28239445">{{cite journal| author=Palovcak A, Liu W, Yuan F, Zhang Y| title=Maintenance of genome stability by Fanconi anemia proteins. | journal=Cell Biosci | year= 2017 | volume= 7 | issue=  | pages= 8 | pmid=28239445 | doi=10.1186/s13578-016-0134-2 | pmc=5320776 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28239445  }} </ref>
**Diagnosis is made by demonstration of DNA crosslinking upon exposure to diepoxybutane (DEB) and mitomycin C (MCC).
**Patients with [[fanconi anemia]] have a higher risk for development of [[Myelodysplastic syndrome|myelodysplastic syndrome (MDS)]] and [[Acute myeloid leukemia|acute myeloid leukemia (AML)]], both of which can contribute to pancytopenia.<ref name="pmid23890415">{{cite journal| author=Du W, Erden O, Pang Q| title=TNF-α signaling in Fanconi anemia. | journal=Blood Cells Mol Dis | year= 2014 | volume= 52 | issue= 1 | pages= 2-11 | pmid=23890415 | doi=10.1016/j.bcmd.2013.06.005 | pmc=3851925 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23890415  }} </ref>
*[[Pearson syndrome]]
**This is a relatively uncommon cause of refractory [[sideroblastic anemia]], [[neutropenia]], and [[thrombocytopenia]].<ref name="pmid1985462">{{cite journal| author=McShane MA, Hammans SR, Sweeney M, Holt IJ, Beattie TJ, Brett EM et al.| title=Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. | journal=Am J Hum Genet | year= 1991 | volume= 48 | issue= 1 | pages= 39-42 | pmid=1985462 | doi= | pmc=1682744 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1985462  }} </ref>
**Clinical features include proximal myopathy and weakness, ophthalmoplegia, ataxia. and peripheral neuropathy.<ref name="pmid1985462">{{cite journal| author=McShane MA, Hammans SR, Sweeney M, Holt IJ, Beattie TJ, Brett EM et al.| title=Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. | journal=Am J Hum Genet | year= 1991 | volume= 48 | issue= 1 | pages= 39-42 | pmid=1985462 | doi= | pmc=1682744 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1985462  }} </ref>
*[[Schwachman-Diamond syndrome]]
**This is a condition that affects approximately 1 in 50000 persons and is characterized by bone marrow failure, pancreatic exocrine insufficiency, and skeletal abnormalities.<ref name="pmid24388329">{{cite journal| author=Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE et al.| title=Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. | journal=J Pediatr | year= 2014 | volume= 164 | issue= 4 | pages= 866-70 | pmid=24388329 | doi=10.1016/j.jpeds.2013.11.039 | pmc=4077327 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24388329  }} </ref>
**It is caused by a biallelic (two alleles) mutation in a ribosomal protein encoded by the Schwachman-Bodian-Diamond gene SBDS, located on chromosome 7.<ref name="pmid24388329">{{cite journal| author=Myers KC, Bolyard AA, Otto B, Wong TE, Jones AT, Harris RE et al.| title=Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. | journal=J Pediatr | year= 2014 | volume= 164 | issue= 4 | pages= 866-70 | pmid=24388329 | doi=10.1016/j.jpeds.2013.11.039 | pmc=4077327 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24388329  }} </ref>
**Clinical manifestations in children usually include diarrhea and steatorrhea (due to pancreatic exocrine insufficiency).<ref name="pmid22935661">{{cite journal| author=Andolina JR, Morrison CB, Thompson AA, Chaudhury S, Mack AK, Proytcheva M et al.| title=Shwachman-Diamond syndrome: diarrhea, no longer required? | journal=J Pediatr Hematol Oncol | year= 2013 | volume= 35 | issue= 6 | pages= 486-9 | pmid=22935661 | doi=10.1097/MPH.0b013e3182667c13 | pmc=3514592 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22935661  }} </ref>
**However, there have been cases of pancytopenia from [[Shwachman-Diamond syndrome|schwachman-diamond syndrome]] in the absence of diarrhea, so this condition should still be in the differential diagnosis of children with pancytopenia and bone marrow failure.
*[[TAR syndrome]]
**This is a rare condition characterized by low platelet count ([[thrombocytopenia]]) and absent radius (a long bone of the lower arm).<ref name="pmid26550033">{{cite journal| author=Tassano E, Gimelli S, Divizia MT, Lerone M, Vaccari C, Puliti A et al.| title=Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP: a new familial case. | journal=Mol Cytogenet | year= 2015 | volume= 8 | issue=  | pages= 87 | pmid=26550033 | doi=10.1186/s13039-015-0188-6 | pmc=4635577 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26550033  }} </ref>
**It is thought to be caused by an interstitial deletion in chromosome 1q21.
**Patients can have skeletal abnormalities (like absent radius, short ulna, and absence of other long bones of the arm).<ref name="pmid26550033">{{cite journal| author=Tassano E, Gimelli S, Divizia MT, Lerone M, Vaccari C, Puliti A et al.| title=Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP: a new familial case. | journal=Mol Cytogenet | year= 2015 | volume= 8 | issue=  | pages= 87 | pmid=26550033 | doi=10.1186/s13039-015-0188-6 | pmc=4635577 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26550033  }} </ref>
**The fingers are not affected.


*Reticular dysgenesis
====Acquired====
*[[Albers-Schonberg disease]]
*[[Banti's Syndrome]]
*[[Bone marrow]] [[tumor]]
*[[Cirrhosis]]
*[[Drug]]s/[[Toxins]]
*[[Felty's Syndrome]]
*[[Gaucher's Disease]]
*[[Graft-versus-host disease]]
*[[Infection]]s
*[[Kala-Azar]]
*[[Leukemia]]
*[[Lymphoma]]
*[[Lymphoproliferative Disorders]]
*[[Myelodysplastic syndrome]]
*[[Myelofibrosis]]
*[[Niemann-Pick Disease]]
*[[Osteoporosis]]
*[[Pernicious anemia]]
*[[Reticulosis]]
*[[Sarcoidosis]]
*[[Thymoma]]
*[[Tuberculosis]]


*[[Rheumatoid disease]]
==Differentiating Pancytopenia from Other Diseases==
{|
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! colspan="3" rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Mechanism
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! colspan="9" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Clinical manifestations
! colspan="8" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para−clinical findings
! colspan="1" rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! rowspan="5" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptoms
| colspan="4" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Signs
|-
! colspan="8" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
|-
! colspan="1" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Special Features
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Splenomegaly
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |CBC
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |PTT
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow infiltration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow failure
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Destruction/
sequestration/
redistribution
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
|-
! rowspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hematologic disorders
! align="center" style="background:#DCDCDC;" |[[Myelodysplastic syndrome (patient information)|Myelodysplastic syndrome]]<ref name="NatelsonPyatt2013">{{cite journal|last1=Natelson|first1=Ethan A.|last2=Pyatt|first2=David|title=Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog|journal=Advances in Hematology|volume=2013|year=2013|pages=1–11|issn=1687-9104|doi=10.1155/2013/309637}}</ref>
| align="left" style="background:#F5F5F5;" |
* [[Bone marrow]] infiltration
* Ineffective [[hematopoiesis]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |−
| align="center" style="background:#F5F5F5;" | ±
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" |Elderly
| align="left" style="background:#F5F5F5;" |Exposure to
* [[Chemotherapy]]
* [[Radiation therapy]]
* [[Tobacco smoking|Tobacco smoke]]
| align="left" style="background:#F5F5F5;" |
* [[Petechia|Petechiae]]
* [[Purpura]]
* Diffuse erythematous [[rash]]
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | Nl
| align="center" style="background:#F5F5F5;" | +
| align="center" style="background:#F5F5F5;" | +
| align="left" style="background:#F5F5F5;" |
* [[Shortness of breath]]
* [[Fatigue]]
* [[Pallor]]
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |↓
| align="center" style="background:#F5F5F5;" |
*Ovalomacrocytosis
*Basophilic stippling
*[[Howell-Jolly body]]
*Dysplastic [[Neutrophil|neutrophils]]
| align="center" style="background:#F5F5F5;" |
*Impaired [[myeloid]] maturation
*[[Congenital dyserythropoietic anemia|Dyserythropoiesis]]
*Dysgranulopoiesis
*Dysmegakaryocytopoiesis
*Hypercellular [[bone marrow]]
*[[Fibrosis]]
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |Nl
| align="center" style="background:#F5F5F5;" |[[Bone marrow examination]] + clinical manifestation
| align="center" style="background:#F5F5F5;" |
*Might transformed to [[acute leukemia]]
|-
! align="left" style="background:#DCDCDC;" |Malignancies such as:<ref name="OshimaYuji2013">{{cite journal|last1=Oshima|first1=Yasuo|last2=Yuji|first2=Koichiro|last3=Tanimoto|first3=Tetsuya|last4=Hinomura|first4=Yasushi|last5=Tojo|first5=Arinobu|title=Association between Acute Myelogenous Leukemia and Thrombopoietin Receptor Agonists in Patients with Immune Thrombocytopenia|journal=Internal Medicine|volume=52|issue=19|year=2013|pages=2193–2201|issn=0918-2918|doi=10.2169/internalmedicine.52.0324}}</ref><ref name="pmid24088751">{{cite journal |vauthors=Oshima Y, Yuji K, Tanimoto T, Hinomura Y, Tojo A |title=Association between acute myelogenous leukemia and thrombopoietin receptor agonists in patients with immune thrombocytopenia |journal=Intern. Med. |volume=52 |issue=19 |pages=2193–201 |date=2013 |pmid=24088751 |doi= |url=}}</ref>
* [[Acute leukemia]]
* [[Chronic leukemia]]
* [[Multiple myeloma]]
* [[Metastasis|Metastatic cancer]]
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow]] infiltration
* Ineffective [[hematopoiesis]]
* Immune mediated
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |Any, more in adults
| align="center" style="background:#F5F5F5;" + |
*Exposure to chemicals
*[[Radiation therapy|Radiation]]
*Pre-existent blood disorders
| align="left" style="background:#F5F5F5;" + |
* [[Petechia|Petechiae]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Muscle weakness|Weakness]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Blast cells
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*[[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" + |Bone marrow examination
| align="left" style="background:#F5F5F5;" + |
*[[Tumor lysis syndrome]]
*[[Infection]]
*[[CNS]] involvement
*[[Disseminated intravascular coagulation|DIC]]
|-
! align="center" style="background:#DCDCDC;" |[[Myelofibrosis]]<ref name="BaePark2013">{{cite journal|last1=Bae|first1=E.|last2=Park|first2=C.-J.|last3=Cho|first3=Y.-U.|last4=Seo|first4=E.-J.|last5=Chi|first5=H.-S.|last6=Jang|first6=S.|last7=Lee|first7=K.-H.|last8=Lee|first8=J.-H.|last9=Lee|first9=J.-H.|last10=Suh|first10=J.-J.|last11=Im|first11=H.-J.|title=Differential diagnosis of myelofibrosis based on WHO 2008 criteria: Acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis|journal=International Journal of Laboratory Hematology|volume=35|issue=6|year=2013|pages=629–636|issn=17515521|doi=10.1111/ijlh.12101}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow]] infiltration
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Average 60 years old
| align="left" style="background:#F5F5F5;" + |
*Exposure to chemicals
*[[Radiation therapy|Radiation]]
*Pre-existent blood disorders
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
* Major [[weight loss]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Muscle weakness|Weakness]]
*[[Fatigue]]
* [[Dyspnea|Shortness of breath]]
* [[Headache]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
* [[Pancytopenia]]
* Hypercellular [[bone marrow]]
* [[Fibrosis]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*[[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" + |Bone marrow examination
| align="left" style="background:#F5F5F5;" + |
* [[Cardiac arrhythmia|Arrhythmia]]
* [[Infection]]
* [[Seizure]]
* May progress to malignancy
|-
! align="center" style="background:#DCDCDC;" |[[Fanconi anemia]]<ref name="ZhangBenedetti2015">{{cite journal|last1=Zhang|first1=Qing-Shuo|last2=Benedetti|first2=Eric|last3=Deater|first3=Matthew|last4=Schubert|first4=Kathryn|last5=Major|first5=Angela|last6=Pelz|first6=Carl|last7=Impey|first7=Soren|last8=Marquez-Loza|first8=Laura|last9=Rathbun|first9=R. Keaney|last10=Kato|first10=Shigeaki|last11=Bagby|first11=Grover C.|last12=Grompe|first12=Markus|title=Oxymetholone Therapy of Fanconi Anemia Suppresses Osteopontin Transcription and Induces Hematopoietic Stem Cell Cycling|journal=Stem Cell Reports|volume=4|issue=1|year=2015|pages=90–102|issn=22136711|doi=10.1016/j.stemcr.2014.10.014}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Genetic disorder|Genetic defect]]
* [[Bone marrow suppression|Bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare  [[autosomal recessive]] genetic disorder, higher in Ashkenazi Jews and Afrikaners in South Africa
| align="left" style="background:#F5F5F5;" + |
* Family history of [[Fanconi anemia]]
| align="left" style="background:#F5F5F5;" + |
* [[Short stature]]
* [[Petechia|Petechiae]] and [[Bruise|bruises]]
* [[Pallor]]
* [[Skin changes|Skin discoloration]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* Skeletal defects
* [[Deafness]]
* [[Ventricular septal defect|VSD]]
* [[Kidney]] abnormalities
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
* [[Pancytopenia]]
* Hypercellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Genetic studies
| align="left" style="background:#F5F5F5;" + |
* Progress to [[Acute myeloid leukemia|acute myelogenous leukemia]]
* [[Neoplasm|Solid tumors]]
* [[Developmental abnormality|Developmental abnormalities]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow infiltration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow failure
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Destruction/
sequestration/
redistribution
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Splenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Aplastic anemia]]<ref name="DolbergLevy2014">{{cite journal|last1=Dolberg|first1=Osnat Jarchowsky|last2=Levy|first2=Yair|title=Idiopathic aplastic anemia: Diagnosis and classification|journal=Autoimmunity Reviews|volume=13|issue=4-5|year=2014|pages=569–573|issn=15689972|doi=10.1016/j.autrev.2014.01.014}}</ref>
| align="left" style="background:#F5F5F5;" + |
*Unknown
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |Biphasic (the young and the elderly)
| align="left" style="background:#F5F5F5;" + |
* Exposure to [[Radiation (medicine)|radiation]], drugs and chemicals, [[pregnancy]], [[Paroxysmal nocturnal hemoglobinuria|PNH]] and viral or [[Autoimmune disease|autoimmune]] causes
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*Large [[Red blood cell|RBCs]]
*Low [[Platelet|platelets]] and [[Granulocyte|granulocytes]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
*replacement of [[bone marrow]] by [[fat]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] +
laboratory findings
| align="left" style="background:#F5F5F5;" + |
*[[Fanconi anemia|Fanconi Anemia]]
*[[Dyskeratosis congenita]]
*[[Shwachman-Diamond syndrome|Schwachman-Diamond syndrome]]
*[[Preleukemia]]
|-
! align="center" style="background:#DCDCDC;" |[[Paroxysmal nocturnal hemoglobinuria]]<ref name="BoyerGrardel2015">{{cite journal|last1=Boyer|first1=Thomas|last2=Grardel|first2=Nathalie|last3=Copin|first3=Marie-Christine|last4=Roumier|first4=Christophe|last5=Touzart|first5=Aurore|last6=Buchdahl|first6=Anne-Laure|last7=Corm|first7=Sélim|last8=de Latour|first8=Régis Peffault|last9=Preudhomme|first9=Claude|last10=Terriou|first10=Louis|title=Paroxysmal nocturnal hemoglobinuria (PNH) and T cell large granular lymphocyte (LGL) leukemia—an unusual association: another cause of cytopenia in PNH|journal=Annals of Hematology|volume=94|issue=10|year=2015|pages=1759–1760|issn=0939-5555|doi=10.1007/s00277-015-2439-3}}</ref>
| align="left" style="background:#F5F5F5;" + |
*Deficiency of [[complement]] regulatory proteins
*[[Mutation|Mutations]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any age
(usually younger adults)
| align="left" style="background:#F5F5F5;" + |
*Sudden [[nocturnal]] [[hemoglobinuria]] with partial clearing during the day
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Thrombosis]]
*Smooth muscle [[dystonia]]
| align="center" style="background:#F5F5F5;" + |↓/Nl
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/Nl
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Cellular [[Bone marrow|marrow]]
*[[Erythroid]] [[hyperplasia]]
*[[dyserythropoiesis]]
* Hypocellular marrow in certain stages of the disease
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |
*[[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" + |[[Flow cytometry]]
| align="left" style="background:#F5F5F5;" + |
*[[Chronic renal failure]]
*[[Pulmonary hypertension]]
*[[Aplastic anemia]]
|-
! align="center" style="background:#DCDCDC;" |[[Disseminated intravascular coagulation]]<ref name="HossainPaidas2013">{{cite journal|last1=Hossain|first1=Nazli|last2=Paidas|first2=Michael J.|title=Disseminated intravascular coagulation|journal=Seminars in Perinatology|volume=37|issue=4|year=2013|pages=257–266|issn=01460005|doi=10.1053/j.semperi.2013.04.008}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Consumption
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
* [[Infection]]
* [[Physical trauma|Trauma]]
* [[Obstetrics]] complications
* [[Cancer]]
* [[Shock]]
| align="left" style="background:#F5F5F5;" + |
* Acutely ill
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
*[[Shortness of breath]]
*[[Fatigue]]
*[[Chest pain]]
| align="center" style="background:#F5F5F5;" + |↓/Nl
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/Nl
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*[[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" + |Lab findings
| align="left" style="background:#F5F5F5;" + |
* High mortality rate
|-
! align="center" style="background:#DCDCDC;" |Dyskeratosis congenital/telomere biology disorders<ref name="PaivaCalado2014">{{cite journal|last1=Paiva|first1=Raquel M.A.|last2=Calado|first2=Rodrigo T.|title=Telomere Dysfunction and Hematologic Disorders|volume=125|year=2014|pages=133–157|issn=18771173|doi=10.1016/B978-0-12-397898-1.00006-2}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Aberrant [[telomere]] biology
* Germline [[Mutation|mutations]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare genetic disorder
| align="left" style="background:#F5F5F5;" + |
* Family history
| align="left" style="background:#F5F5F5;" + |
* [[Isolated congenital nail dysplasia|Nail dysplasia]]
* Abnormal [[Human skin color|skin pigmentation]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Leukoplakia|Oral leukoplakia]]
* [[Shortness of breath]]
*[[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical findings + genetic studies
| align="left" style="background:#F5F5F5;" + |
* Progress to [[Cancer|malignancy]]
* [[Idiopathic pulmonary fibrosis|Pulmonary fibrosis]]
* [[Hepato-biliary diseases|Liver disease]]
|-
! align="center" style="background:#DCDCDC;" |[[Shwachman-Diamond syndrome]]<ref name="GokceTuncer2012">{{cite journal|last1=Gokce|first1=Muge|last2=Tuncer|first2=Murat|last3=Cetin|first3=Mualla|last4=Gumruk|first4=Fatma|title=Molecular Diagnosis of Shwachman-Diamond Syndrome Presenting with Pancytopenia at an Early Age: The First Report from Turkey|journal=Indian Journal of Hematology and Blood Transfusion|volume=29|issue=3|year=2012|pages=161–163|issn=0971-4502|doi=10.1007/s12288-012-0163-x}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Germline [[Mutation|mutations]]
* [[Bone marrow suppression|Bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare genetic disorder
| align="left" style="background:#F5F5F5;" + |
* Family history
| align="left" style="background:#F5F5F5;" + |
* Skeletal abnormalities
* [[Short stature]]
* [[Metaphyseal dysostosis mental retardation conductive deafness|Metaphyseal dysostosis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Steatorrhea]]
* [[Delayed milestone|Growth retardation]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical findings + genetic studies
| align="left" style="background:#F5F5F5;" + |
* [[Pancreatic insufficiency|Exocrine pancreatic insufficiency]]
* [[Delayed milestone|Growth retardation]]
* Increased frequency of [[Infection|infections]]
|-
! rowspan="6" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Immunology/
Rheumatology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow infiltration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow failure
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Destruction/
sequestration/
redistribution
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Splenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[SLE]]<ref name="NewmanOwlia2013">{{cite journal|last1=Newman|first1=Kam|last2=Owlia|first2=Mohammad Bagher|last3=El-Hemaidi|first3=Ihab|last4=Akhtari|first4=Mojtaba|title=Management of immune cytopenias in patients with systemic lupus erythematosus — Old and new|journal=Autoimmunity Reviews|volume=12|issue=7|year=2013|pages=784–791|issn=15689972|doi=10.1016/j.autrev.2013.02.001}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |More in young females
| align="left" style="background:#F5F5F5;" + |
* Family history
| align="left" style="background:#F5F5F5;" + |
* [[Rash|Skin rash]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* [[Weight loss]]
* [[Oral ulcer|Mouth ulcers]]
* [[Chest pain]]
* [[Lymphadenopathy]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="left" style="background:#F5F5F5;" + |
*[[Hemoglobinuria]]
*[[Proteinuria]]
| align="center" style="background:#F5F5F5;" + |Clinical findings + laboratory studies
| align="left" style="background:#F5F5F5;" + |
* Multi organ damage
* Poor prognosis
|-
! align="center" style="background:#DCDCDC;" |[[Felty's syndrome|Felty syndrome]]<ref name="LiatsosTsironi2018">{{cite journal|last1=Liatsos|first1=George D.|last2=Tsironi|first2=Ioanna|last3=Vassilopoulos|first3=Dimitrios|last4=Dourakis|first4=Spyridon|title=Severe pancytopenia and splenomegaly associated with felty's syndrome, both fully responsive solely to corticosteroids|journal=Clinical Case Reports|volume=6|issue=3|year=2018|pages=509–512|issn=20500904|doi=10.1002/ccr3.1396}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Rare [[autoimmune disease]], more in females 50-70 years old
| align="left" style="background:#F5F5F5;" + |
* History of [[rheumatoid arthritis]]
| align="left" style="background:#F5F5F5;" + |
* [[Pallor]]
* [[Hyperpigmentation|Skin hyperpigmentation]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
* Painful, stiff, and swollen [[Joint|joints]]
* [[Keratoconjunctivitis sicca]]
* [[Weight loss]]
* [[Fatigue]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical findings + laboratory studies
| align="left" style="background:#F5F5F5;" + |
* [[Rheumatoid arthritis]]
* [[Infection|Infections]]
|-
! align="center" style="background:#DCDCDC;" |[[Wiskott-Aldrich syndrome|Wiskott Aldrich syndrome]]<ref name="pmid1960605">{{cite journal |vauthors=Brochstein JA, Gillio AP, Ruggiero M, Kernan NA, Emanuel D, Laver J, Small T, O'Reilly RJ |title=Marrow transplantation from human leukocyte antigen-identical or haploidentical donors for correction of Wiskott-Aldrich syndrome |journal=J. Pediatr. |volume=119 |issue=6 |pages=907–12 |date=December 1991 |pmid=1960605 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Mutation in [[GATA1|GATA-1]]
* Immune mediated [[bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare [[Sex-linked|X-linked]] [[Recessive gene|recessive]] disease
| align="left" style="background:#F5F5F5;" + |
* [[Immunodeficiency]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
*[[Eczema]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
* [[Dysentery|Bloody diarrhea]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
*Small but low [[Platelet|platelets]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Genetic study
| align="left" style="background:#F5F5F5;" + |
*Recurrent [[Infection|infections]]
*[[Autoimmune disease|autoimmune disorders]]
*[[Cancer|Malignancy]]
|-
! align="center" style="background:#DCDCDC;" |[[GATA2]] deficiency<ref name="SanyiJaye2018">{{cite journal|last1=Sanyi|first1=Allen|last2=Jaye|first2=David L.|last3=Rosand|first3=Cecilia B.|last4=Box|first4=Amanda|last5=Shanmuganathan|first5=Chandrakasan|last6=Waller|first6=Edmund K.|title=Diagnosis of GATA2 haplo-insufficiency in a young woman prompted by pancytopenia with deficiencies of B-cell and dendritic cell development|journal=Biomarker Research|volume=6|issue=1|year=2018|issn=2050-7771|doi=10.1186/s40364-018-0127-x}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare
| align="left" style="background:#F5F5F5;" + |
* [[Immunodeficiency]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
*[[Purpura]]
*[[Petechia|Petechiae]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Genetic study
| align="left" style="background:#F5F5F5;" + |
*Recurrent [[Infection|infections]]
*[[Autoimmune disease|autoimmune disorders]]
*[[Cancer|Malignancy]]
|-
! align="center" style="background:#DCDCDC;" |[[Hemophagocytic lymphohistiocytosis]]<ref name="Larroche2012">{{cite journal|last1=Larroche|first1=Claire|title=Hemophagocytic lymphohistiocytosis in adults: Diagnosis and treatment|journal=Joint Bone Spine|volume=79|issue=4|year=2012|pages=356–361|issn=1297319X|doi=10.1016/j.jbspin.2011.10.015}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Immune mediated [[Bone marrow suppression|bone marrow failure]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare
| align="left" style="background:#F5F5F5;" + |
* [[Immunodeficiency]]
* Positive family history
| align="left" style="background:#F5F5F5;" + |
*[[Purpura]]
*[[Petechia|Petechiae]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Genetic study
| align="left" style="background:#F5F5F5;" + |
*Recurrent [[Infection|infections]]
*[[Autoimmune disease|autoimmune disorders]]
*[[Cancer|Malignancy]]
|-
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |GI disorders
! align="center" style="background:#DCDCDC;" |[[Portal hypertension]]/[[cirrhosis]]<ref name="SarinKhanna2014">{{cite journal|last1=Sarin|first1=Shiv K.|last2=Khanna|first2=Rajeev|title=Non-cirrhotic Portal Hypertension|journal=Clinics in Liver Disease|volume=18|issue=2|year=2014|pages=451–476|issn=10893261|doi=10.1016/j.cld.2014.01.009}}</ref><ref name="AksoyKoklu2015">{{cite journal|last1=Aksoy|first1=Evrim K.|last2=Koklu|first2=Seyfettin|title=Albendazole-Induced Cirrhosis Decompensation and Pancytopenia|journal=Annals of Pharmacotherapy|volume=49|issue=8|year=2015|pages=945–946|issn=1060-0280|doi=10.1177/1060028015590178}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Splenomegaly]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*[[Cirrhosis]]
*[[Alcoholism|Alcohol use]]
| align="left" style="background:#F5F5F5;" + |
*[[Purpura]]
*[[Petechia|Petechiae]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Portal vein thrombosis]]
*[[Hepatorenal syndrome]]
*Variceal hemorrhage
*Hepatic [[hydrothorax]]
*[[Spontaneous bacterial peritonitis]]
|-
! align="center" style="background:#DCDCDC;" |[[Glycogen storage disease|Storage diseases]] (eg, [[Gaucher's disease|Gaucher]])<ref name="Düzenli KarÖzdemir2018">{{cite journal|last1=Düzenli Kar|first1=Yeter|last2=Özdemir|first2=Zeynep C.|last3=Kiral|first3=Eylem|last4=Kiliç Yildirim|first4=Gonca|last5=Dinleyici|first5=Ener Ç.|last6=Bör|first6=Özcan|title=Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease|journal=Journal of Pediatric Hematology/Oncology|year=2018|pages=1|issn=1077-4114|doi=10.1097/MPH.0000000000001208}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Splenomegaly]]
* [[Bone marrow]] infiltration
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Rare in children
| align="left" style="background:#F5F5F5;" + |
* Family history
| align="left" style="background:#F5F5F5;" + |
* [[Rash|Skin rash]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
|-
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Infections
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow infiltration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow failure
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Destruction/
sequestration/
redistribution
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Splenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|-
! align="center" style="background:#DCDCDC;" |[[Sepsis]]<ref name="TendasNiscola2010">{{cite journal|last1=Tendas|first1=Andrea|last2=Niscola|first2=Pasquale|last3=Dentamaro|first3=Teresa|last4=Cupelli|first4=Luca|last5=Di Matteo|first5=Gigliola|last6=Finocchi|first6=Andrea|last7=Siniscalchi|first7=Agostina|last8=Fratoni|first8=Stefano|last9=Scimò|first9=Teresa|last10=Scaramucci|first10=Laura|last11=Giovannini|first11=Marco|last12=Ales|first12=Micaela|last13=Pio Perrotti|first13=Alessio|last14=de Fabritiis|first14=Paolo|title=Pancytopenia and severe sepsis in an adult case of congenital X-linked agammaglobulinemia (XLA)|journal=Annals of Hematology|volume=89|issue=9|year=2010|pages=949–951|issn=0939-5555|doi=10.1007/s00277-009-0891-7}}</ref>
| align="left" style="background:#F5F5F5;" + |
*Direct [[bone marrow suppression]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*[[Infection|Bacterial infection]]
| align="left" style="background:#F5F5F5;" + |
*[[Petechiae]]
*[[Purpura]]
*[[Erythema]]
*[[Ulcer|Ulceration]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |Nl to ↓
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |±
| align="left" style="background:#F5F5F5;" + |
*[[Malaise]]
*[[Lymphadenopathy]]
| align="center" style="background:#F5F5F5;" + |↓/↑
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓/↑
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + | +
Depends on the etiology
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + culture
| align="left" style="background:#F5F5F5;" + |
*Associated with ↑ mortality
|-
! align="center" style="background:#DCDCDC;" |[[Infection|Viral infection]] such as [[Human Immunodeficiency Virus (HIV)|HIV]], [[hepatitis]], [[Epstein Barr virus|Epstein-Barr virus]]<ref name="Santiago-RodríguezMayor2015">{{cite journal|last1=Santiago-Rodríguez|first1=Eduardo|last2=Mayor|first2=Angel|last3=Fernández-Santos|first3=Diana|last4=Hunter-Mellado|first4=Robert|title=Profile of HIV-Infected Hispanics with Pancytopenia|journal=International Journal of Environmental Research and Public Health|volume=13|issue=1|year=2015|pages=38|issn=1660-4601|doi=10.3390/ijerph13010038}}</ref>
| align="left" style="background:#F5F5F5;" + |
* [[Bone marrow suppression]]
* [[Splenomegaly]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*High risk behaviors
*Close contact
| align="left" style="background:#F5F5F5;" + |
*[[Petechiae]]
*[[Purpura]]
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |±
| align="center" style="background:#F5F5F5;" + |±
| align="left" style="background:#F5F5F5;" + |
*[[Lymphadenopathy]]
*[[Muscle weakness]]
*[[Joint swelling]]
*Focal neurological deficits
*Depends on etiology
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="left" style="background:#F5F5F5;" + |
*[[Hematuria]]
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + lab tests
| align="left" style="background:#F5F5F5;" + |
*Depends on etiology
*[[Encephalomyelitis]]
|-
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Nutritional
! align="center" style="background:#DCDCDC;" |[[Macrocytic anemia|Megaloblastic anemia]]<ref name="pmid24669609">{{cite journal |vauthors=Khattak MB, Ismail M, Marwat ZI, Khan F |title=Frequency and characterisation of pancytopenia in megaloblastic anaemia |journal=J Ayub Med Coll Abbottabad |volume=24 |issue=3-4 |pages=53–5 |date=2012 |pmid=24669609 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Ineffective [[hematopoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*[[Malnutrition]]
*[[Alcoholism|Alcohol use]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Fatigue]]
*[[Weakness]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Laboratory findings
| align="center" style="background:#F5F5F5;" + |NA
|-
! align="center" style="background:#DCDCDC;" |Excessive [[alcohol]]<ref name="pmid3671238">{{cite journal |vauthors=Weston CF, Hall MJ |title=Pancytopenia and folate deficiency in alcoholics |journal=Postgrad Med J |volume=63 |issue=736 |pages=117–20 |date=February 1987 |pmid=3671238 |pmc=2428237 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Ineffective [[hematopoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Alcoholism
| align="left" style="background:#F5F5F5;" + |
*History of [[Alcoholism|alcohol use]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="left" style="background:#F5F5F5;" + |
*[[Hepatomegaly]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Clinical manifestation
| align="left" style="background:#F5F5F5;" + |
*[[Chronic liver disease]]
|-
! align="center" style="background:#DCDCDC;" |Other nutritional deficiency such as [[copper deficiency]], [[zinc]] toxicity<ref name="pmid23652881">{{cite journal |vauthors=Hudspeth M, Turner A, Miller N, Lazarchick J |title=Pancytopenia after allogeneic bone marrow transplant due to copper deficiency |journal=J. Pediatr. Hematol. Oncol. |volume=36 |issue=4 |pages=316–8 |date=May 2014 |pmid=23652881 |doi=10.1097/MPH.0b013e318290c644 |url=}}</ref><ref name="pmid24082414">{{cite journal |vauthors=Robinson SD, Cooper B, Leday TV |title=Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass surgery |journal=Proc (Bayl Univ Med Cent) |volume=26 |issue=4 |pages=382–6 |date=October 2013 |pmid=24082414 |pmc=3777101 |doi= |url=}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Ineffective [[hematopoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*[[Malnutrition]]
*[[Alcoholism|Alcohol use]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Fatigue]]
*[[Weakness]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Laboratory findings
| align="center" style="background:#F5F5F5;" + |NA
|-
! align="center" style="background:#DCDCDC;" |[[Malnutrition]]<ref name="DragusinMurray2015">{{cite journal|last1=Dragusin|first1=Roxana C.|last2=Murray|first2=Jean-Michel|last3=Mallet|first3=Dominique|last4=Gonzalez|first4=Hugo|last5=Markou|first5=Georges A.|title=Pancytopenia related to malnutrition during pregnancy|journal=International Journal of Gynecology & Obstetrics|volume=130|issue=1|year=2015|pages=86–87|issn=00207292|doi=10.1016/j.ijgo.2015.02.020}}</ref>
| align="left" style="background:#F5F5F5;" + |
* Ineffective [[hematopoiesis]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any
| align="left" style="background:#F5F5F5;" + |
*[[Malnutrition]]
*[[Alcoholism|Alcohol use]]
| align="left" style="background:#F5F5F5;" + |
* Normal
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="left" style="background:#F5F5F5;" + |
*[[Fatigue]]
*[[Weakness]]
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Laboratory findings
| align="center" style="background:#F5F5F5;" + |NA
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Medications
! align="left" style="background:#DCDCDC;" |Medications such as:<ref name="pmid22862866">{{cite journal |vauthors=Kelm DJ, Torres KM, Sohail MR |title=46-year-old man with fevers, chills, and pancytopenia |journal=Mayo Clin. Proc. |volume=87 |issue=8 |pages=799–802 |date=August 2012 |pmid=22862866 |pmc=3498402 |doi=10.1016/j.mayocp.2012.03.012 |url=}}</ref><ref name="pmid24937727">{{cite journal |vauthors=Davis SA, Krowchuk DP, Feldman SR |title=Prescriptions for a toxic combination: use of methotrexate plus trimethoprim-sulfamethoxazole in the United States |journal=South. Med. J. |volume=107 |issue=5 |pages=292–3 |date=May 2014 |pmid=24937727 |doi=10.1097/SMJ.0000000000000098 |url=}}</ref>
* [[Chemotherapy|Cytotoxic drugs]]
* Idiosyncratic reactions to medications
| align="left" style="background:#F5F5F5;" + |
* Immune destruction
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Patients with [[Cancer|malignancy]]
| align="left" style="background:#F5F5F5;" + |
*[[Radiation therapy|Radiation]]
*[[Cancer]]
| align="left" style="background:#F5F5F5;" + |
*[[Purpura]]
*[[Petechia|Petechiae]]
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |−
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="left" style="background:#F5F5F5;" + |
*[[Pancytopenia]]
| align="left" style="background:#F5F5F5;" + |
*Hypocellular [[bone marrow]]
*Megakaryocytic hypoplasia or aplasia
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |↑
| align="center" style="background:#F5F5F5;" + |[[Hematuria case study one|Hematuria]]
| align="center" style="background:#F5F5F5;" + |Clinical manifestation + exclusion of the other causes
| align="left" style="background:#F5F5F5;" + |
*[[Thrombosis]]
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Category
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Condition
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Etiology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow infiltration
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow failure
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Destruction/
sequestration/
redistribution
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Congenital
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Acquried
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Demography
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |History
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Fever
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bleeding
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |BP
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Splenomegaly
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Jaundice
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Other signs
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Plt
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |HB
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |WBC
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PBS
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Bone marrow exam
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |PTT
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |UA
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Gold standard
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
|}
 
==Epidemiology and Demographics==
* Pancytopenia affects males and females equally.
* However, the underlying etiologies of pancytopenia can have a gender predilection.
* Please see above sections for epidemiology and demographics of the individual disease entities that cause pancytopenia.


*[[Severe combined immunodeficiency]], T- B+ due to JAK3 deficiency
==Risk Factors==
* The risk factors of pancytopenia are related to the underlying cause.
* For example, leukemia-mediated pancytopenia can be related to risk factors such as chemical exposure, [[radiation]], or family history.
* Please see above sections for risk factors of the individual disease entities that cause pancytopenia.


*[[Sickle cell disease]]
==Screening==
* There are no suggested screening tests for pancytopenia.
* The [[United States Preventive Services Task Force|United States Preventive Services Task Force (USPSTF)]] does not have any recommendations for screening for pancytopenia.
* However, if a person is suspected of having a particular condition that cause cause pancytopenia, such as viral infection, a diagnosis [[complete blood count]] (CBC) can be checked to assess for pancytopenia.


*[[Sulfonamides ]]
==Natural History, Complications, and Prognosis==
===Natural History===
* The natural history of pancytopenia is dictated by the pathophysiology of the under etiology.
* For example, viral-mediated pancytopenia is typically short-lived, pending clearance of the [[virus]].
* Drug-induced pancytopenia typically resolves after discontinuing of the culprit drug and the drug has been metabolized by the body.
* [[Leukemia]]-mediated pancytopenia is usually a more long-term process, as marrow replacement by leukemia cells is difficult to overcome unless the leukemia is treated and the patient is in remission.
* Please see above sections for natural history of the individual disease entities that cause pancytopenia.


*[[Systemic lupus erythematosus]]
===Complications===
* Complications of pancytopenia relate to deficits of the cell types that are affected.
* Decrease in [[Red blood cell|erythrocytes]] causes [[fatigue]], [[pallor]], [[Dizziness|lightheadedness]], and shortness of breath due to decrease in oxygen delivery to tissue beds.
* Decrease in [[leukocytes]] and leukocyte subsets causes infections, which can be viral, bacteria, fungal, or parasitic.
* The most concerning complication of decrease in leukocytes is called febrile [[neutropenia]], which is a hematologic emergency.
* Decrease in [[Platelet|thrombocytes]] causes bleeding, which is typically mucosal, given loss of the ability of platelets to create a hemostatic plug.


*[[Tamoxifen]]
===Prognosis===
* The prognosis of pancytopenia is related to the underlying etiology.
* For example, patients with unfavorable-risk leukemia will likely have a poor prognosis from a pancytopenia perspective.
* Patients with viral-mediated pancytopenia have a prognosis that is determined by the natural history of the virus.
* [[Epstein Barr virus|Epstein-Barr virus (EBV)]]-related pancytopenia can have a good prognosis if EBV resolves.
* Drug-induced pancytopenia has a favorable prognosis, as discontinuation of the offending agent can typically reverse the pancytopenia.
* Please see above sections for prognosis of the individual disease entities that cause pancytopenia.


*[[Thymoma ]]
==Diagnosis==
===Diagnostic Criteria===
The diagnosis of pancytopenia is made by assessing a [[complete blood count]] (CBC) when all of the following criteria are fulfilled:
*Anemia as defined by hemoglobin level < 12 grams per [[deciliter]] (g/dl)
*Leukopenia as defined by leukocyte count < 4000 per [[microliter]]
*Thrombocytopenia as defined by platelet count < 150000 per [[microliter]]


*[[Thyroid carcinoma]]
===History and Symptoms===
Symptoms of pancytopenia are related to decrease in [[erythrocytes]], [[leukocytes]], and [[platelets]].
*Decrease in erythrocytes causes [[fatigue]], [[shortness of breath]], decreased exercise tolerance, and [[pallor]].
*Decrease in leukocytes causes [[infection]], which can affect a multitude of organ systems including the central nervous system, lungs, abdomen, urinary tract, kidneys, and skin.
*Decrease in platelets causes mucocutaneous bleeding, typically of the nose, mouth, gastrointestinal tract, or genitourinary tract.


*[[Tobacco use ]]
===Physical Examination===
Key components of the physical exam include assessment of the conjunctiva, oral and nasal mucosa, lymph nodes (cervical, axillary, supraclavicular, inguinal), spleen size, liver size, and skin.


*Topoisomerase II interactive agents
* The anemia component of pancytopenia can cause conjunctival pallor, mucosal pallor, skin pallor, and tachypnea.
* The leukopenia component of pancytopenia can cause variable findings depending on whether infection is present. Exam findings can include lymphadenopathy, egophony, coarse breath sounds, malodorous urine, suprapubic tenderness, costovertebral tenderness, abdominal tenderness, skin erythema, and/or skin purulence.
* The thrombocytopenia component of pancytopenia can cause petechiae (pinpoint hemorrhages in the skin), mucosal bleeding, or internal bleeding.


*[[Trisomy]] 8 mosaicism
===Laboratory Findings===
Laboratory findings in pancytopenia are, by definition:
* Hemoglobin level < 12 grams per [[deciliter]] (g/dl)
* Leukocyte count < 4000 per [[microliter]]
* Platelet count < 150000 per [[microliter]]


*[[Valganciclovir hydrochloride]]
Other laboratory findings, depending on the underlying cause, can include:
* Elevated LDH
* Elevated indirect bilirubin
* Elevated reticulocyte count
* Decreased haptoglobin


*[[Vitamin B12 deficiency]]
===Imaging Findings===
* There are no imaging findings associated with pancytopenia.


*[[Vitamin C deficiency]]
===Other Diagnostic Studies===
* Viral [[polymerase chain reaction]] [[PCR]] testing can be done for viral-induced pancytopenia. This includes PCR for CMV DNA and EBV DNA.


*[[Wiskott-Aldrich syndrome]]
==Treatment==
===Medical Therapy===
* The treatment of pancytopenia depends on the underlying cause.
* If pancytopenia is due to medication adverse effect, the offending agent should be discontinued.
* If pancytopenia is due to [[myelopthisis]] from leukemia, the underlying leukemia should be treated with cytotoxic chemotherapy.
* If pancytopenia is due to [[aplastic anemia]], this should be treated with either immunosuppression with [[anti-thymocyte globulin]] (ATG) and [[cyclosporine A]], or by hematopoietic stem cell transplantation from a matched related donor.
* Please see above sections for details of treatment of the individual disease entities that cause pancytopenia.


*[[Xeroderma pigmentosum]]
===Surgery===
* The is no role for surgery for pancytopenia.
* However, for [[immune thrombocytopenia purpura]] (ITP) and [[autoimmune hemolytic anemia]] (AIHA), splenectomy can be considered.


{{col-end}}
===Prevention===
* The prevention of pancytopenia focuses on prevention of the underlying etiologies.
* For example, viral-induced pancytopenia can be prevented by taking precautions against acquiring viral infections.
* This can include good hand hygiene, avoidance of exposures, anti-viral medications as prophylaxis.
* Prevention of leukemia-induced pancytopenia can be achieved via avoidance of risk factors of leukemia such as radiation exposure, chemical exposure, or benzene exposure.
* Drug-induced pancytopenia can be prevented by choosing an alternative medication in a similar class that does not cause pancytopenia.
* For example, in a patient who requires prophylaxis for PCP, atovaquone can be administered in place of trimethoprim-sulfamethoxazole, as atovaquone does not cause pancytopenia.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Blood tests]]


[[Category:Hematology]]
[[Category:Hematology]]
 
[[Category:Crowdiagnosis]]
[[Category:Oncology]]
[[Category:Oncology]]
[[Category:Oncology stub]]


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Latest revision as of 22:19, 10 January 2020


Pancytopenia is not equivalent with bone marrow suppression. Pancytopenia is a lab finding that may related to either bone marrow suppression or peripheral sequestration/destruction. For details about bone marrow suppression click here.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Ogheneochuko Ajari, MB.BS, MS [3], Shyam Patel [4], Sadaf Sharfaei M.D.[5]

Overview

Pancytopenia is the reduction in numbers of all three bone marrow cell types, including red blood cells, white blood cells, and platelets. The prefix "pan-" means "everything," "cyto" means "cell", and the suffix "penia" means "deficiency." Pancytopenia is not a disease, but rather a laboratory finding that may related to bone marrow suppression caused by either insufficient production (aplastic anemia), inability of cells to mature (myelodysplasia), replacement of normal bone marrow with fibrosis (myelofibrosis) or peripheral sequestration that is not related to the bone marrow (e.g. splenomegaly or hypersplenism). Chemotherapy is associated with pancytopenia due to drug-mediated bone marrow suppression. Pancytopenia frequently requires a bone marrow biopsy in order to distinguish among different causes.

Historical Perspective

The history of pancytopenia relates to the history of each of its individual sub-entities, namely anemia, thrombocytopenia, and leukopenia. Pancytopenia was not recognized as a distinct clinical entity until after each of its other subcomponents were characterized. Thus, there is no specific history for pancytopenia.

  • History of aplastic anemia:
    • The seminal discoveries for aplastic anemia were made by Bruno Speck and Georges Mathe, who noted that immunosuppression could be used to treat aplastic anemia.[1]
    • In the 1970s, matched sibling donor transplant was used for severe aplastic anemia.[2]
  • History of paroxysmal nocturnal hemoglobinuria:
    • In 1882, Dr. Paul Strubing reported the case of a patient with hematuria at night that occurred periodically.[3]
      • He noted that hemolysis was the reason for the patient's hematuria.
    • In 1925, the term paroxysmal nocturnal hemaglobinuria was coined.[3]
    • In the 1930s, Dr. T.H. Ham noted that acidified serum could induce hemolysis.
      • Thus, the Ham's acid serum test was developed.[3]
      • This became the first diagnostic test for this disease.
    • In the 1950s, the complement pathway was discovered, and it was determined that paroxysmal nocturnal hemoglobinuria was due to activation of complement proteins on the red blood cell membrane.[3]
    • In the 1980s, the genetic defect responsible for the disease was discovered, specifically, the PIG-A gene defect leading to inability to anchor complement-inhibitory proteins onto the red blood cell membrane.

Classification

There is no classification system for pancytopenia. However, some underlying disease entities that cause pancytopenia have classification. For example, aplastic anemia is classified as moderate, severe, or very severe.

Pathophysiology

  • The pathophysiology of pancytopenia relates to the underlying etiology.
  • In most cases, pancytopenia is due to a disruption in trilineage hematopoiesis.
  • This means that the bone marrow is not appropriately producing erythrocytes, leukocytes, and thrombocytocytes.
  • The cause of the disruption in trilineage hematopoiesis is in turn due to the underlying cause of pancytopenia.
  • For example, viral-mediated pancytopenia is caused by viral particles infecting hematopoietic cells and preventing normal cell division.
  • Leukemia-mediated pancytopenia is typically due to marrow replacement of normal hematopoietic precursors, a process known as myelopthisis.
  • Leukemic infiltration of the bone marrow creates a "crowding-out" phenomenon.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of pancytopenia that require acute treatment within 24 hours. However, if pancytopenia is accompanied by fever, this should be treated as a hematologic emergency with prompt administration of IV antibiotics.

Common Causes

  • Aplastic anemia [4]
    • This is a condition characterized by immune-mediated reduction in all three hematopoietic cell lines with absence of hematopoietic precursors.[1]
    • It is a rare condition with a prevalence of only 1-2 cases per million annually. It is most commonly diagnosed in childhood.
    • Epidemiologic studies have shown a greater prevalence in Southeast Asia and other countries with limited access to healthcare, as viral infection can trigger aplastic crisis.[1]
    • There are three categories: moderate, severe, and very severe.
    • These categories are based upon the number and degree of cytopenias as well as bone marrow cellularity.
    • The preferred treatment of aplastic anemia is bone marrow transplantation from an HLA-matched sibling.
    • If there is no human leukocyte antigen (HLA)-matched sibling available, the next best option is medical management with the immunosuppressive agents anti-thymocyte globulin (ATG) and cyclosporine A.[1]
    • The reason for the efficacy of immunosuppressive medications is that the pancytopenia from aplastic anemia is due to abnormal immune activation and thus destruction of hematopoietic cells.
    • ATG from horse has been shown to be superior compared to ATG from rabbit.[1]
    • ATG is administered over 5 days, and cyclosporine A is administered orally for 6 months, after which response can be assessed.
    • The combination of ATG and cyclosporine A carries a response rate of 60-70%. [2] Eltrombopag can also be added to the regimen of ATG and cyclosporine.
  • Folate deficiency
    • Folate is required for pyrimidine nucleotide synthesis, and thus folate deficiency can lead to decreased production of hematopoietic cells.[5]
    • Folate deficiency occurs in persons who consume large amounts of alcohol.
    • Folate deficiency is accompanied by macrocytosis, or large-sized cells.
    • Treatment of folate deficiency is supplementation of folate in the diet.
  • Leishmaniasis
    • This is a rare infectious cause of pancytopenia.
  • Leukemia
    • This can be myeloid or lymphoid, and each of these can be acute or chronic.
    • Acute leukemias typically cause pancytopenia via a crowding-out phenomenon, known as myelopthisis.
    • Diagnosis of acute leukemia is based by demonstration of blast count of 20% or greater in the bone marrow.
    • Treatment involves multiagent chemotherapy, such as cytarabine combined with anthracycline for acute myeloid leukemia, or vincristine-based and anthracycline-based regimen for acute lymphoblastic leukemia.
    • Treatment of the underlying leukemia can help improve pancytopenia.
  • Megaloblastic anemia [4]
    • This condition is characterized by decreased red blood cell count and increased cellular size with defective maturation.[6]
    • The cause is usually deficiency of vitamin B12 or folate.
    • The diagnosis is made with a complete blood count showing hemoglobin less than 12 g/dl, mean corpuscular volume greater than 100 femtoliter (MCV > 100 fL), and peripheral smear showing enlarged cells.
    • The treatment is supplementation with vitamin B12 or folate.[6]
  • Myelodysplastic syndrome
    • This is a disease characterized by ineffective erythropoiesis and peripheral cytopenias.
    • It is a clonal disorder of the hematopoietic stem cell.[7]
    • The subtype of myelodysplastic syndrome that causes pancytopenia is termed refractory anemia with multilineage dysplasia.
    • The pancytopenia of myelodysplastic syndrome is due to failure of maturation of hematopoietic precursors, leading to peripheral cytopenias.[7]
    • Diagnosis of myelodysplastic syndrome is made by demonstration of at least 1 cell line with 10% of greater dysplastic cells on bone marrow biopsy.
    • Bone marrow biopsy should also show myeloblasts less then 20% of total leukocytes.
    • Clinical features of myelodysplastic syndrome include manifestations of specific cytopenias, such as fatigue if there is anemia, bleeding if there is thrombocytopenia, and infections if there is leukopenia.[8]
    • The prognostication of myelodysplastic syndrome is determined by the International Prognosis Scoring System-Revised (IPSS-R), which is determined by blast count, the karyotype, and cytopenia.
    • This clinical tool is used to estimate the time to progression to acute myeloid leukemia.
    • The treatment of myelodysplastic syndrome is based on the subtype. Lenalidomide is highly effective for persons with deletion of chromosome 5q.[8]
    • DNA hypomethylating agents like azacitadine and decitabine are commonly used for those with symptomatic cytopenias and without chromosome 5q deletion.
    • In some cases, allogeneic stem cell transplantation can be done with the goal of curing myelodysplastic syndrome and preventing progression to acute myeloid leukemia.[8]
    • Adjunctive therapies include transfusion support (such as red blood cell transfusions or platelet transfusions), growth factor support (such as filgrastim), and immunosuppressive therapy, which is particularly effective in persons with PNH clones, HLA-DR15 positivity, or STAT3-mutant cytotoxic T cells.
  • Paroxysmal nocturnal hemoglobinuria
    • This is a clonal disorder of the hematopoietic stem cell characterized by hemolysis due to complement activation on the red blood cell membrane.[9]
    • It is cause of bone marrow failure.
    • The genetic defect is a deficiency in glycosylphosphatidylinositol (GPI) which is encoded by the PIG-A gene.
    • This protein normally serves to anchor complement regulatory and inhibitory proteins onto the red blood cell membrane.[9]
    • The two major regulatory proteins are CD55 (or decay accelerating factor (DAF)), which functions to degrade complement proteins C3 and C5 convertase, and CD59 (or membrane inhibitor of reactive lysis (MIRL)), which functions to prevent complement-mediated hemolysis via preventing formation of the membrane attack complex.[9]
    • The clinical manifestations include hematuria, portal venous or hepatic venous thrombosis.
    • Diagnosis is made by performing flow cytometry of peripheral blood and analyzing the expression fo CD55 and CD59 on red blood cell membranes.[9]
    • Treatment of this condition is eculizumab, a humanized monoclonal antibody that inhibits complement protein C5.[9]
  • Viral infections
    • Viruses such as HIV, EBV, or CMV can cause pancytopenia.
    • The diagnosis can be made by checking viral loads via PCR of peripheral blood or by checking antibody titers to the viruses.
    • For example, EBV can be diagnosed by assessing for EBV DNA PCR, or by assessing for IgM or IgM to EBV antigens.
  • Vitamin B12 deficiency
  • Copper deficiency
    • This is a more rare cause of pancytopenia.
  • Zinc deficiency
    • This is a more rare cause of pancytopenia. Treatment is supplementation with zinc.

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning Arsenic poisoning, arsenicals, benzene solvents, genotoxic therapy, glue vapors, gold, mutagen exposure, mutagen-detoxification (GSTq1-null), radium chloride, toxins, valproic acid poisoning
Dental No underlying causes
Dermatologic Chediak-Higashi disease, dyskeratosis congenita, eosinophilic fasciitis, melanoma, reticular dysgenesis, reticulosis, systemic lupus erythematosus, xeroderma pigmentosum
Drug Side Effect Acetaminophen and Oxycodone, aclarubicin, albendazole, alemtuzumab, alkylating antineoplastic agent, auranofin, azathioprine, aztreonam, boceprevir, busulfan, carbamazepine, carboplatin, cefadroxil, ceftazidime, certolizumab pegol, chemotherapy, chloramphenicol, chlorpromazine, chlorpropamide, cromolyn, cidofovir, clomipramine, cyclophosphamide, cytotoxic drugs, dactinomycin, docetaxel, doxorubicin, ethosuximide, febuxostat, flucytosine, gemcitabine, gemifloxacin mesylate, genotoxic therapy, idarubicin, Imipenem-Cilastatin,indomethacin , infliximab, interferon beta-1a, lincomycin hydrochloride, minocycline hydrochloride, non steroidal anti-inflammatory drugs, ofatumumab, omacetaxine, oxaprozin, oxcarbazepine, penicillamine, phenacemide , phenylbutazone, piperacillin, pralatrexate, propylthiouracil, pyrimethamine, rabeprazole, sulfonamides , tamoxifen, temozolomide, thiothixene, tolazamide, tolbutamide, topoisomerase II interactive agents, trifluoperazine, trimethadione, trimethoprim-sulfamethoxazole, valganciclovir hydrochloride
Ear Nose Throat Dubowitz syndrome, Jacobsen syndrome
Endocrine Osteoporosis, panhypopituitarism, thyroid carcinoma
Environmental No underlying causes
Gastroenterologic Banti's syndrome, cirrhosis, Gaucher's disease, hepatosplenic T-cell lymphoma, hypersplenism, intrinsic factor deficiency, malabsorption syndrome, Plummer-Vinson syndrome, portal hypertension, sarcoidosis, Schwachman-Diamond syndrome, splenomegaly
Genetic Albers-Schonberg disease, ataxia telangiectasia, Banti's syndrome, Bloom syndrome , cartilage-hair hypoplasia, Chediak-Higashi disease, Diamond-Blackfan anemia, DNA repair-deficiency disorder, Down syndrome, Dubowitz syndrome, dyskeratosis congenita, familial histiocytic reticulosis, familial monosomy 7, Fanconi anemia, Gaucher's disease, hemophagocytic lymphohistiocytosis, Hoyeraal-Hreidarsson syndrome, Jacobsen syndrome, intrinsic factor deficiency, neurofibromatosis 1, Niemann-Pick disease, osteopetrosis lethal, osteopetrosis, autosomal recessive 2, Pearson syndrome, Schwachman-Diamond syndrome, severe combined immunodeficiency, TAR syndrome, trisomy 8 mosaicism, Wiskott-Aldrich syndrome, xeroderma pigmentosum
Hematologic Acute lymphoblastic leukemia, acute myeloid leukemia, aggressive NK-cell leukemia, amegakaryocytic thrombocytopenia, aplastic anemia, autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2, bleeding (Excessive), bone marrow tumor, Castleman's disease, chronic lymphocytic leukaemia, chronic myeloid leukaemia, cyclical neutropenia, Diamond-Blackfan anemia, familial histiocytic reticulosis, familial myelofibrosis, Fanconi anemia, Gaucher's disease, hairy cell leukemia, hematopoietic stem cell transplantation, hemoglobin E disease, hemoglobin H disease, hemoglobin SC disease, hemophagocytic lymphohistiocytosis , hepatosplenic T-cell lymphoma, histiocytosis X, Hodgkin's lymphoma, hypersplenism, hypoplastic myelodysplastic syndromes, ineffective erythropoiesis, intestinal lymphangiectasia, intrinsic factor deficiency, iron deficiency, langerhans cell histiocytosis, leucoerythroblastic anemia, leukemia, lymphoma, malignant histiocytosis, megaloblastic anemia, myelodysplastic syndrome, myelofibrosis, myeloma, myelopathic anemia, non-Hodgkin lymphoma, paroxysmal nocturnal hemoglobinuria, Pearson syndrome, pernicious anemia, Plummer-Vinson syndrome, precursor B acute lymphoblastic leukemia, reticulosis, Schwachman-Diamond syndrome, sickle cell disease, TAR syndrome, t-cell large granular lymphocytic leukemia, Wiskott-Aldrich syndrome
Iatrogenic Radiation therapy, radioactive p32
Infectious Disease Babesiosis, brucellosis, dengue, Epstein-Barr virus , hepatitis, human immunodeficiency virus , infectious mononucleosis, kala-azar, Kikuchi disease, lassa fever, legionella pneumophila, mycobacterium tuberculosis, parvovirus B19 infection, Q fever, tuberculosis, viral infections, Whipple's disease
Musculoskeletal/Orthopedic Albers-Schonberg disease, ankylosing spondylitis, cartilage-hair hypoplasia, Ewing's sarcoma, osteoclastoma, osteopetrosis lethal, osteopetrosis, autosomal recessive 2, osteoporosis, osteosarcoma, TAR syndrome
Neurologic Ataxia telangiectasia, Down syndrome , neuroblastoma, neurofibromatosis 1, Niemann-Pick disease
Nutritional/Metabolic Anorexia nervosa, copper deficiency, folate deficiency, Gaucher's disease, glutathione synthase deficiency, iron deficiency, kwashiorkor, marasmus, obesity, vitamin B12 deficiency, vitamin C deficiency
Obstetric/Gynecologic Pregnancy
Oncologic Acute lymphoblastic leukemia, acute myeloid leukemia, aggressive NK-cell leukemia, bone marrow tumor, cancer, chondrosarcoma, chronic lymphocytic leukaemia, chronic myeloid leukaemia, epiphyseal tumors, Ewing's sarcoma, familial myelofibrosis, germ cell tumors , granuloma, hairy cell leukemia, hepatosplenic T-cell lymphoma, histiocytosis X, Hodgkin's lymphoma, hypoplastic myelodysplastic syndromes, langerhans cell histiocytosis, leukemia, lymphoma, melanoma, metastatic neoplasm, myelodysplastic syndrome, myelofibrosis, myeloma, neuroblastoma, non-Hodgkin lymphoma, osteoclastoma, osteosarcoma, precursor B acute lymphoblastic leukemia, prostate cancer, t-cell large granular lymphocytic leukemia, thymoma, thyroid carcinoma
Ophthalmologic No underlying causes
Overdose/Toxicity Colchicine toxicity
Psychiatric Anorexia nervosa
Pulmonary Sarcoidosis
Renal/Electrolyte Renal failure, chronic, systemic lupus erythematosus
Rheumatology/Immunology/Allergy Ankylosing spondylitis, auto-immune disorders, autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2, Castleman's disease, common variable hypogammaglobulinemia, common variable immune deficiency, eosinophilic fasciitis , Felty's syndrome, graft versus host disease, histiocytosis X, langerhans cell histiocytosis, rheumatoid disease, sarcoidosis, severe combined immunodeficiency, systemic lupus erythematosus, Wiskott-Aldrich syndrome
Sexual No underlying causes
Trauma No underlying causes
Urologic Prostate cancer
Miscellaneous Idiopathic, radioactive p32, tobacco use

Causes in Alphabetical Order

Causes by Pathophysiology

Bone Marrow Failure

Peripheral Sequestration/Destruction

Causes by Mode of Inheritance

This is not applicable since there is no specific mode of inheritance for pancytopenia.

Congenital

  • Cartilage hair hypoplasia:
    • This is a bone marrow failure condition caused by ribosomal protein mutations.[45]
    • Clinical manifestations include cartilage and hair loss.
  • Diamond-Blackfan syndrome:
    • This is a rare condition affecting 5-7 persons per million and is characterized by a macrocytic anemia and less than 5% erythroid precursors including reticulocytes.[46]
    • It is the most common inherited erythrocyte failure syndrome, and it is inherited in an autosomal dominant pattern.[45]
    • This condition is caused by mutations in ribosomal protein genes such as RPS19.
    • Though neutropenia and thrombocytopenia do not usually occur, moderate white blood cell and platelet count reductions have been described in some cases.[46]
    • Fetal hemoglobin is typically increased in an effect to enhance delivery of oxygen to tissues in the setting of low hemoglobin.[46]
    • Clinical manifestations usually include short statute, ocular abnormalities, skeletal abnormalities.
    • It is the most common inherited erythrocyte failure syndrome.[45]
    • The only curative therapy is bone marrow transplantation.
  • Dubowitz syndrome
    • This is a rare autosomal recessive disorder characterized by increased cancer susceptibility.[47]
    • The exact genetic abnormality and etiology is yet to be identified.
    • Patients have DNA that is very sensitive to ionizing radiation and a few chemotherapy agents like anthracyclines and bleomycin.[47]
    • There is some clinical overlap with Fanconi anemia.[47]
    • Patients can develop bone marrow failure and cytopenias.
  • Dyskeratosis congenita
    • This is a rare condition caused by short telomeres, which normally function to maintain the length and integrity of DNA.[48]
    • It is characterized by skin abnormalities, nail abnormalities, and leukoplakia.
    • The genes implicated include DKC1 (dyskerin), TERT, and TERC.
    • Other genes implicated in this condition encode ribonucleoprotein enzymes.
    • By age 30, approximately 80% of patients with this condition will develop bone marrow failure.[48]
  • Fanconi's anemia
    • This is a condition characterized by erythrocyte hypoproduction due to genomic instability and increased susceptibility to DNA damaging agents.[45] [49]
    • Diagnosis is made by demonstration of DNA crosslinking upon exposure to diepoxybutane (DEB) and mitomycin C (MCC).
    • Patients with fanconi anemia have a higher risk for development of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), both of which can contribute to pancytopenia.[50]
  • Pearson syndrome
  • Schwachman-Diamond syndrome
    • This is a condition that affects approximately 1 in 50000 persons and is characterized by bone marrow failure, pancreatic exocrine insufficiency, and skeletal abnormalities.[52]
    • It is caused by a biallelic (two alleles) mutation in a ribosomal protein encoded by the Schwachman-Bodian-Diamond gene SBDS, located on chromosome 7.[52]
    • Clinical manifestations in children usually include diarrhea and steatorrhea (due to pancreatic exocrine insufficiency).[53]
    • However, there have been cases of pancytopenia from schwachman-diamond syndrome in the absence of diarrhea, so this condition should still be in the differential diagnosis of children with pancytopenia and bone marrow failure.
  • TAR syndrome
    • This is a rare condition characterized by low platelet count (thrombocytopenia) and absent radius (a long bone of the lower arm).[54]
    • It is thought to be caused by an interstitial deletion in chromosome 1q21.
    • Patients can have skeletal abnormalities (like absent radius, short ulna, and absence of other long bones of the arm).[54]
    • The fingers are not affected.

Acquired

Differentiating Pancytopenia from Other Diseases

Category Condition Etiology Mechanism Congenital Acquried Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs
Lab Findings
Special Features Fever Bleeding BP Splenomegaly Jaundice Other CBC PBS Bone marrow exam PT PTT UA
Bone marrow infiltration Bone marrow failure Destruction/

sequestration/ redistribution

Plt HB WBC
Hematologic disorders Myelodysplastic syndrome[55] + + ± + Elderly Exposure to + + Nl + + Nl Nl Nl Bone marrow examination + clinical manifestation
Malignancies such as:[56][57] + + + ± ± Any, more in adults
  • Exposure to chemicals
  • Radiation
  • Pre-existent blood disorders
+ + Nl +
  • Blast cells
Bone marrow examination
Myelofibrosis[58] + + + + Average 60 years old
  • Exposure to chemicals
  • Radiation
  • Pre-existent blood disorders
+ + Nl + Bone marrow examination
Fanconi anemia[59] + + Rare autosomal recessive genetic disorder, higher in Ashkenazi Jews and Afrikaners in South Africa + Nl Nl Nl Nl Genetic studies
Condition Etiology Bone marrow infiltration Bone marrow failure Destruction/

sequestration/ redistribution

Congenital Acquried Demography History Appearance Fever Bleeding BP Splenomegaly Jaundice Other signs Plt HB WBC PBS Bone marrow exam PT PTT UA Gold standard Associated findings
Aplastic anemia[60]
  • Unknown
+ ± ± Biphasic (the young and the elderly) + Nl Nl Bone marrow examination +

laboratory findings

Paroxysmal nocturnal hemoglobinuria[61] + + + Any age

(usually younger adults)

  • Normal
Nl ↓/Nl ↓/Nl Nl Nl Flow cytometry
Disseminated intravascular coagulation[62]
  • Consumption
+ + Any
  • Acutely ill
+ + + ↓/Nl ↓/Nl NA Lab findings
  • High mortality rate
Dyskeratosis congenital/telomere biology disorders[63] + + Rare genetic disorder
  • Family history
+ Nl + Nl Nl Nl Clinical findings + genetic studies
Shwachman-Diamond syndrome[64] + + Rare genetic disorder
  • Family history
+ Nl + Nl Nl Nl Clinical findings + genetic studies
Immunology/

Rheumatology

Condition Etiology Bone marrow infiltration Bone marrow failure Destruction/

sequestration/ redistribution

Congenital Acquried Demography History Appearance Fever Bleeding BP Splenomegaly Jaundice Other signs Plt HB WBC PBS Bone marrow exam PT PTT UA Gold standard Associated findings
SLE[65] + + + + More in young females
  • Family history
+ + Nl to ↓ + + Clinical findings + laboratory studies
  • Multi organ damage
  • Poor prognosis
Felty syndrome[66] + + Rare autoimmune disease, more in females 50-70 years old + + Nl + + Nl Nl Nl Clinical findings + laboratory studies
Wiskott Aldrich syndrome[67] + + Rare X-linked recessive disease + Nl Nl Nl Nl Genetic study
GATA2 deficiency[68] + + Rare + + + Nl Nl Nl Genetic study
Hemophagocytic lymphohistiocytosis[69] + + Rare + + + Nl Nl Nl Genetic study
GI disorders Portal hypertension/cirrhosis[70][71] + + Any + + + Nl Clinical manifestation
Storage diseases (eg, Gaucher)[72] + + + Rare in children
  • Family history
+ + +
Infections Condition Etiology Bone marrow infiltration Bone marrow failure Destruction/

sequestration/ redistribution

Congenital Acquried Demography History Appearance Fever Bleeding BP Splenomegaly Jaundice Other signs Plt HB WBC PBS Bone marrow exam PT PTT UA Gold standard Associated findings
Sepsis[73] + + + Any + ± Nl to ↓ ± ↓/↑ ↓/↑ NA +

Depends on the etiology

Clinical manifestation + culture
  • Associated with ↑ mortality
Viral infection such as HIV, hepatitis, Epstein-Barr virus[74] + + + Any
  • High risk behaviors
  • Close contact
+ Nl ± ± Nl Nl Clinical manifestation + lab tests
Nutritional Megaloblastic anemia[29] + + Any
  • Normal
Nl Nl Nl Nl Laboratory findings NA
Excessive alcohol[5] + + Alcoholism
  • Normal
Nl + + Nl Clinical manifestation
Other nutritional deficiency such as copper deficiency, zinc toxicity[75][76] + + Any
  • Normal
Nl Nl Nl Nl Laboratory findings NA
Malnutrition[77] + + Any
  • Normal
Nl Nl Nl Nl Laboratory findings NA
Medications Medications such as:[78][79]
  • Immune destruction
+ + Patients with malignancy + Nl
  • Hypocellular bone marrow
  • Megakaryocytic hypoplasia or aplasia
Hematuria Clinical manifestation + exclusion of the other causes
Category Condition Etiology Bone marrow infiltration Bone marrow failure Destruction/

sequestration/ redistribution

Congenital Acquried Demography History Appearance Fever Bleeding BP Splenomegaly Jaundice Other signs Plt HB WBC PBS Bone marrow exam PT PTT UA Gold standard Associated findings

Epidemiology and Demographics

  • Pancytopenia affects males and females equally.
  • However, the underlying etiologies of pancytopenia can have a gender predilection.
  • Please see above sections for epidemiology and demographics of the individual disease entities that cause pancytopenia.

Risk Factors

  • The risk factors of pancytopenia are related to the underlying cause.
  • For example, leukemia-mediated pancytopenia can be related to risk factors such as chemical exposure, radiation, or family history.
  • Please see above sections for risk factors of the individual disease entities that cause pancytopenia.

Screening

  • There are no suggested screening tests for pancytopenia.
  • The United States Preventive Services Task Force (USPSTF) does not have any recommendations for screening for pancytopenia.
  • However, if a person is suspected of having a particular condition that cause cause pancytopenia, such as viral infection, a diagnosis complete blood count (CBC) can be checked to assess for pancytopenia.

Natural History, Complications, and Prognosis

Natural History

  • The natural history of pancytopenia is dictated by the pathophysiology of the under etiology.
  • For example, viral-mediated pancytopenia is typically short-lived, pending clearance of the virus.
  • Drug-induced pancytopenia typically resolves after discontinuing of the culprit drug and the drug has been metabolized by the body.
  • Leukemia-mediated pancytopenia is usually a more long-term process, as marrow replacement by leukemia cells is difficult to overcome unless the leukemia is treated and the patient is in remission.
  • Please see above sections for natural history of the individual disease entities that cause pancytopenia.

Complications

  • Complications of pancytopenia relate to deficits of the cell types that are affected.
  • Decrease in erythrocytes causes fatigue, pallor, lightheadedness, and shortness of breath due to decrease in oxygen delivery to tissue beds.
  • Decrease in leukocytes and leukocyte subsets causes infections, which can be viral, bacteria, fungal, or parasitic.
  • The most concerning complication of decrease in leukocytes is called febrile neutropenia, which is a hematologic emergency.
  • Decrease in thrombocytes causes bleeding, which is typically mucosal, given loss of the ability of platelets to create a hemostatic plug.

Prognosis

  • The prognosis of pancytopenia is related to the underlying etiology.
  • For example, patients with unfavorable-risk leukemia will likely have a poor prognosis from a pancytopenia perspective.
  • Patients with viral-mediated pancytopenia have a prognosis that is determined by the natural history of the virus.
  • Epstein-Barr virus (EBV)-related pancytopenia can have a good prognosis if EBV resolves.
  • Drug-induced pancytopenia has a favorable prognosis, as discontinuation of the offending agent can typically reverse the pancytopenia.
  • Please see above sections for prognosis of the individual disease entities that cause pancytopenia.

Diagnosis

Diagnostic Criteria

The diagnosis of pancytopenia is made by assessing a complete blood count (CBC) when all of the following criteria are fulfilled:

  • Anemia as defined by hemoglobin level < 12 grams per deciliter (g/dl)
  • Leukopenia as defined by leukocyte count < 4000 per microliter
  • Thrombocytopenia as defined by platelet count < 150000 per microliter

History and Symptoms

Symptoms of pancytopenia are related to decrease in erythrocytes, leukocytes, and platelets.

  • Decrease in erythrocytes causes fatigue, shortness of breath, decreased exercise tolerance, and pallor.
  • Decrease in leukocytes causes infection, which can affect a multitude of organ systems including the central nervous system, lungs, abdomen, urinary tract, kidneys, and skin.
  • Decrease in platelets causes mucocutaneous bleeding, typically of the nose, mouth, gastrointestinal tract, or genitourinary tract.

Physical Examination

Key components of the physical exam include assessment of the conjunctiva, oral and nasal mucosa, lymph nodes (cervical, axillary, supraclavicular, inguinal), spleen size, liver size, and skin.

  • The anemia component of pancytopenia can cause conjunctival pallor, mucosal pallor, skin pallor, and tachypnea.
  • The leukopenia component of pancytopenia can cause variable findings depending on whether infection is present. Exam findings can include lymphadenopathy, egophony, coarse breath sounds, malodorous urine, suprapubic tenderness, costovertebral tenderness, abdominal tenderness, skin erythema, and/or skin purulence.
  • The thrombocytopenia component of pancytopenia can cause petechiae (pinpoint hemorrhages in the skin), mucosal bleeding, or internal bleeding.

Laboratory Findings

Laboratory findings in pancytopenia are, by definition:

Other laboratory findings, depending on the underlying cause, can include:

  • Elevated LDH
  • Elevated indirect bilirubin
  • Elevated reticulocyte count
  • Decreased haptoglobin

Imaging Findings

  • There are no imaging findings associated with pancytopenia.

Other Diagnostic Studies

Treatment

Medical Therapy

  • The treatment of pancytopenia depends on the underlying cause.
  • If pancytopenia is due to medication adverse effect, the offending agent should be discontinued.
  • If pancytopenia is due to myelopthisis from leukemia, the underlying leukemia should be treated with cytotoxic chemotherapy.
  • If pancytopenia is due to aplastic anemia, this should be treated with either immunosuppression with anti-thymocyte globulin (ATG) and cyclosporine A, or by hematopoietic stem cell transplantation from a matched related donor.
  • Please see above sections for details of treatment of the individual disease entities that cause pancytopenia.

Surgery

Prevention

  • The prevention of pancytopenia focuses on prevention of the underlying etiologies.
  • For example, viral-induced pancytopenia can be prevented by taking precautions against acquiring viral infections.
  • This can include good hand hygiene, avoidance of exposures, anti-viral medications as prophylaxis.
  • Prevention of leukemia-induced pancytopenia can be achieved via avoidance of risk factors of leukemia such as radiation exposure, chemical exposure, or benzene exposure.
  • Drug-induced pancytopenia can be prevented by choosing an alternative medication in a similar class that does not cause pancytopenia.
  • For example, in a patient who requires prophylaxis for PCP, atovaquone can be administered in place of trimethoprim-sulfamethoxazole, as atovaquone does not cause pancytopenia.

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