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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.

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
- This can cause megaloblastic anemia.^[6]
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

Insufficient production (aplastic anemia)
Inability of cells or mature (myelodysplasia)
Replacement of normal bone marrow with fibrosis (myelofibrosis)

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
- This is a relatively uncommon cause of refractory sideroblastic anemia, neutropenia, and thrombocytopenia.^[51]
- Clinical features include proximal myopathy and weakness, ophthalmoplegia, ataxia. and peripheral neuropathy.^[51]
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				Para−clinical findings
										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					Special Features	Fever	Bleeding	BP	Splenomegaly	Jaundice	Other	Plt	HB	WBC	PBS	Bone marrow exam	PT	PTT	UA
Hematologic disorders	Myelodysplastic syndrome^[55]	Bone marrow infiltration Ineffective hematopoiesis	+	+	−	±	+	Elderly	Exposure to Chemotherapy Radiation therapy Tobacco smoke	Petechiae Purpura Diffuse erythematous rash	+	+	Nl	+	+	Shortness of breath Fatigue Pallor	↓	↓	↓	Ovalomacrocytosis Basophilic stippling Howell-Jolly body Dysplastic neutrophils	Impaired myeloid maturation Dyserythropoiesis Dysgranulopoiesis Dysmegakaryocytopoiesis Hypercellular bone marrow Fibrosis	Nl	Nl	Nl	Bone marrow examination + clinical manifestation	Might transformed to acute leukemia
	Malignancies such as:^[56]^[57] Acute leukemia Chronic leukemia Multiple myeloma Metastatic cancer	Bone marrow infiltration Ineffective hematopoiesis Immune mediated	+	+	+	±	±	Any, more in adults	Exposure to chemicals Radiation Pre-existent blood disorders	Petechiae	+	+	Nl	+	−	Weakness	↓	↓	↓	Pancytopenia	Blast cells	↑	↑	Hemoglobinuria	Bone marrow examination	Tumor lysis syndrome Infection CNS involvement DIC
	Myelofibrosis^[58]	Bone marrow infiltration	+	+	−	+	+	Average 60 years old	Exposure to chemicals Radiation Pre-existent blood disorders	Pallor Major weight loss	+	+	Nl	+	−	Weakness Fatigue Shortness of breath Headache	↓	↓	↓	Pancytopenia	Pancytopenia Hypercellular bone marrow Fibrosis	↑	↑	Hemoglobinuria	Bone marrow examination	Arrhythmia Infection Seizure May progress to malignancy
	Fanconi anemia^[59]	Genetic defect Bone marrow failure	−	+	−	+	−	Rare autosomal recessive genetic disorder, higher in Ashkenazi Jews and Afrikaners in South Africa	Family history of Fanconi anemia	Short stature Petechiae and bruises Pallor Skin discoloration	−	+	Nl	−	−	Skeletal defects Deafness VSD Kidney abnormalities	↓	↓	↓	Pancytopenia	Pancytopenia Hypercellular bone marrow	Nl	Nl	Nl	Genetic studies	Progress to acute myelogenous leukemia Solid tumors Developmental abnormalities
	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)	Exposure to radiation, drugs and chemicals, pregnancy, PNH and viral or autoimmune causes	Pallor	−	+	Nl	−	−	Shortness of breath Fatigue	↓	↓	↓	Large RBCs Low platelets and granulocytes	Hypocellular bone marrow replacement of bone marrow by fat	↑	↑	Nl	Bone marrow examination + laboratory findings	Fanconi Anemia Dyskeratosis congenita Schwachman-Diamond syndrome Preleukemia
	Paroxysmal nocturnal hemoglobinuria^[61]	Deficiency of complement regulatory proteins Mutations	+	+	−	−	+	Any age (usually younger adults)	Sudden nocturnal hemoglobinuria with partial clearing during the day	Normal	−	−	Nl	−	−	Thrombosis Smooth muscle dystonia	↓/Nl	↓	↓/Nl	Pancytopenia	Cellular marrow Erythroid hyperplasia dyserythropoiesis Hypocellular marrow in certain stages of the disease	Nl	Nl	Hemoglobinuria	Flow cytometry	Chronic renal failure Pulmonary hypertension Aplastic anemia
	Disseminated intravascular coagulation^[62]	Consumption	−	−	+	−	+	Any	Infection Trauma Obstetrics complications Cancer Shock	Acutely ill	+	+	↓	−	+	Shortness of breath Fatigue Chest pain	↓/Nl	↓	↓/Nl	Pancytopenia	NA	↑	↑	Hemoglobinuria	Lab findings	High mortality rate
	Dyskeratosis congenital/telomere biology disorders^[63]	Aberrant telomere biology Germline mutations	−	+	−	+	−	Rare genetic disorder	Family history	Nail dysplasia Abnormal skin pigmentation	−	+	Nl	−	+	Oral leukoplakia Shortness of breath Fatigue	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Clinical findings + genetic studies	Progress to malignancy Pulmonary fibrosis Liver disease
	Shwachman-Diamond syndrome^[64]	Germline mutations Bone marrow failure	−	+	−	+	−	Rare genetic disorder	Family history	Skeletal abnormalities Short stature Metaphyseal dysostosis	−	+	Nl	−	+	Steatorrhea Growth retardation	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Clinical findings + genetic studies	Exocrine pancreatic insufficiency Growth retardation Increased frequency of infections
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]	Immune mediated bone marrow failure	−	+	+	+	+	More in young females	Family history	Skin rash	+	+	Nl to ↓	+	+	Weight loss Mouth ulcers Chest pain Lymphadenopathy	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	↑	↑	Hemoglobinuria Proteinuria	Clinical findings + laboratory studies	Multi organ damage Poor prognosis
	Felty syndrome^[66]	Immune mediated bone marrow failure	−	+	−	−	+	Rare autoimmune disease, more in females 50-70 years old	History of rheumatoid arthritis	Pallor Skin hyperpigmentation	+	+	Nl	+	+	Painful, stiff, and swollen joints Keratoconjunctivitis sicca Weight loss Fatigue	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Clinical findings + laboratory studies	Rheumatoid arthritis Infections
	Wiskott Aldrich syndrome^[67]	Mutation in GATA-1 Immune mediated bone marrow failure	−	+	−	+	−	Rare X-linked recessive disease	Immunodeficiency Positive family history	Eczema	−	+	Nl	−	−	Bloody diarrhea	↓	↓	↓	Pancytopenia	Hypocellular bone marrow Small but low platelets	Nl	Nl	Nl	Genetic study	Recurrent infections autoimmune disorders Malignancy
	GATA2 deficiency^[68]	Immune mediated bone marrow failure	−	+	−	+	−	Rare	Immunodeficiency Positive family history	Purpura Petechiae	−	+	↓	+	+	−	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Genetic study	Recurrent infections autoimmune disorders Malignancy
	Hemophagocytic lymphohistiocytosis^[69]	Immune mediated bone marrow failure	−	+	−	+	−	Rare	Immunodeficiency Positive family history	Purpura Petechiae	−	+	↓	+	+	−	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Genetic study	Recurrent infections autoimmune disorders Malignancy
GI disorders	Portal hypertension/cirrhosis^[70]^[71]	Splenomegaly	−	−	+	−	+	Any	Cirrhosis Alcohol use	Purpura Petechiae	−	+	↓	+	+	−	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	↑	↑	Nl	Clinical manifestation	Portal vein thrombosis Hepatorenal syndrome Variceal hemorrhage Hepatic hydrothorax Spontaneous bacterial peritonitis
GI disorders	Storage diseases (eg, Gaucher)^[72]	Splenomegaly Bone marrow infiltration	+	−	+	+	−	Rare in children	Family history	Skin rash	−	+	↓	+	+	−	↓	↓	↓	Pancytopenia	Hypocellular bone marrow
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]	Direct bone marrow suppression	+	+	−	−	+	Any	Bacterial infection	Petechiae Purpura Erythema Ulceration	+	±	Nl to ↓	−	±	Malaise Lymphadenopathy	↓/↑	↓	↓/↑	Pancytopenia	NA	↑	↑	+ Depends on the etiology	Clinical manifestation + culture	Associated with ↑ mortality
	Viral infection such as HIV, hepatitis, Epstein-Barr virus^[74]	Bone marrow suppression Splenomegaly	−	+	+	−	+	Any	High risk behaviors Close contact	Petechiae Purpura	+	−	Nl	±	±	Lymphadenopathy Muscle weakness Joint swelling Focal neurological deficits Depends on etiology	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Hematuria	Clinical manifestation + lab tests	Depends on etiology Encephalomyelitis
Nutritional	Megaloblastic anemia^[29]	Ineffective hematopoiesis	−	+	−		+	Any	Malnutrition Alcohol use	Normal	−	−	Nl	−	−	Fatigue Weakness	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Laboratory findings	NA
	Excessive alcohol^[5]	Ineffective hematopoiesis	−	+	−	−	+	Alcoholism	History of alcohol use	Normal	−	−	Nl	+	+	Hepatomegaly	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	↑	↑	Nl	Clinical manifestation	Chronic liver disease
	Other nutritional deficiency such as copper deficiency, zinc toxicity^[75]^[76]	Ineffective hematopoiesis	−	+	−	−	+	Any	Malnutrition Alcohol use	Normal	−	−	Nl	−	−	Fatigue Weakness	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Laboratory findings	NA
	Malnutrition^[77]	Ineffective hematopoiesis	−	+	−	−	+	Any	Malnutrition Alcohol use	Normal	−	−	Nl	−	−	Fatigue Weakness	↓	↓	↓	Pancytopenia	Hypocellular bone marrow	Nl	Nl	Nl	Laboratory findings	NA
Medications	Medications such as:^[78]^[79] Cytotoxic drugs Idiosyncratic reactions to medications	Immune destruction	−	+	−	−	+	Patients with malignancy	Radiation Cancer	Purpura Petechiae	−	+	Nl	−	−	−	↓	↓	↓	Pancytopenia	Hypocellular bone marrow Megakaryocytic hypoplasia or aplasia	↑	↑	Hematuria	Clinical manifestation + exclusion of the other causes	Thrombosis
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:

Hemoglobin level < 12 grams per deciliter (g/dl)
Leukocyte count < 4000 per microliter
Platelet count < 150000 per microliter

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

Viral polymerase chain reaction PCR testing can be done for viral-induced pancytopenia. This includes PCR for CMV DNA and EBV DNA.

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

The is no role for surgery for pancytopenia.
However, for immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA), splenectomy can be considered.

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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[Larroche2012-69] Larroche, Claire (2012). "Hemophagocytic lymphohistiocytosis in adults: Diagnosis and treatment". Joint Bone Spine. 79 (4): 356–361. doi:10.1016/j.jbspin.2011.10.015. ISSN 1297-319X.

[SarinKhanna2014-70] Sarin, Shiv K.; Khanna, Rajeev (2014). "Non-cirrhotic Portal Hypertension". Clinics in Liver Disease. 18 (2): 451–476. doi:10.1016/j.cld.2014.01.009. ISSN 1089-3261.

[AksoyKoklu2015-71] Aksoy, Evrim K.; Koklu, Seyfettin (2015). "Albendazole-Induced Cirrhosis Decompensation and Pancytopenia". Annals of Pharmacotherapy. 49 (8): 945–946. doi:10.1177/1060028015590178. ISSN 1060-0280.

[Düzenli_KarÖzdemir2018-72] Düzenli Kar, Yeter; Özdemir, Zeynep C.; Kiral, Eylem; Kiliç Yildirim, Gonca; Dinleyici, Ener Ç.; Bör, Özcan (2018). "Hemophagocytic Lymphohystiocytosis Associated With Type Ia Glycogen Storage Disease". Journal of Pediatric Hematology/Oncology: 1. doi:10.1097/MPH.0000000000001208. ISSN 1077-4114.

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[Santiago-RodríguezMayor2015-74] Santiago-Rodríguez, Eduardo; Mayor, Angel; Fernández-Santos, Diana; Hunter-Mellado, Robert (2015). "Profile of HIV-Infected Hispanics with Pancytopenia". International Journal of Environmental Research and Public Health. 13 (1): 38. doi:10.3390/ijerph13010038. ISSN 1660-4601.

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@@ Line 4: / Line 4: @@
 {{SI}}
-{{CMG}}; {{AE}} {{CZ}}, {{Ochuko}}, {{shyam}}
+{{CMG}}; {{AE}} {{CZ}}, {{Ochuko}}, {{shyam}}, {{SSH}}
 ==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 or 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). or destruction (such as [[hemolytic anemia]]. [[HIV]] ([[human immunodeficiency virus]]) is itself a cause of pancytopenia. 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 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==
@@ Line 54: / Line 54: @@
 ** [[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.
-** 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>
+** 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]]
 ** 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>
@@ Line 222: / Line 222: @@
 ===Causes in Alphabetical Order===
-{{columns-list|3|
+{{columns-list|
 *[[Acetaminophen and Oxycodone]]
 *[[Aclarubicin]]
@@ Line 536: / Line 536: @@
 ! colspan="8" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
 |-
-! colspan="1" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Appearance
+! 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
@@ Line 560: / Line 560: @@
 |-
 ! rowspan="10" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Hematologic disorders
-! align="center" style="background:#DCDCDC;" |[[Myelodysplastic syndrome (patient information)|Myelodysplastic syndrome]]
+! 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
@@ Line 570: / Line 570: @@
 | align="center" style="background:#F5F5F5;" | +
 | align="center" style="background:#F5F5F5;" |Elderly
-| align="center" style="background:#F5F5F5;" |Exposure to
+| align="left" style="background:#F5F5F5;" |Exposure to
 * [[Chemotherapy]]
 * [[Radiation therapy]]
 * [[Tobacco smoking|Tobacco smoke]]
-| align="center" style="background:#F5F5F5;" |
+| align="left" style="background:#F5F5F5;" |
 * [[Petechia|Petechiae]]
 * [[Purpura]]
@@ Line 583: / Line 583: @@
 | align="center" style="background:#F5F5F5;" | +
 | align="center" style="background:#F5F5F5;" | +
-| align="center" style="background:#F5F5F5;" |
+| align="left" style="background:#F5F5F5;" |
 * [[Shortness of breath]]
 * [[Fatigue]]
@@ Line 609: / Line 609: @@
 *Might transformed to [[acute leukemia]]
 |-
-! align="left" style="background:#DCDCDC;" |Malignancies such as:
+! 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]]
@@ Line 628: / Line 628: @@
 *[[Radiation therapy|Radiation]]
 *Pre-existent blood disorders
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Petechia|Petechiae]]
 | align="center" style="background:#F5F5F5;" + | +
@@ Line 635: / Line 635: @@
 | align="center" style="background:#F5F5F5;" + | +
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Pancytopenia]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Blast cells
-*
 | align="center" style="background:#F5F5F5;" + |↑
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Tumor lysis syndrome]]
 *[[Infection]]
@@ Line 656: / Line 655: @@
 *[[Disseminated intravascular coagulation|DIC]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Myelofibrosis]]
+! 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
@@ Line 665: / Line 664: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Average 60 years old
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Exposure to chemicals
 *[[Radiation therapy|Radiation]]
 *Pre-existent blood disorders
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pallor]]
 * Major [[weight loss]]
@@ Line 677: / Line 676: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Muscle weakness|Weakness]]
 *[[Fatigue]]
@@ Line 685: / Line 684: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pancytopenia]]
+* Hypercellular [[bone marrow]]
-*Hypercellular [[bone marrow]]
+* [[Fibrosis]]
-*[[Fibrosis]]
 | align="center" style="background:#F5F5F5;" + |↑
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Cardiac arrhythmia|Arrhythmia]]
 * [[Infection]]
@@ Line 703: / Line 701: @@
 * May progress to malignancy
 |-
-! align="center" style="background:#DCDCDC;" |[[Fanconi anemia]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Genetic disorder|Genetic defect]]
 * [[Bone marrow suppression|Bone marrow failure]]
@@ Line 713: / Line 711: @@
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Family history of [[Fanconi anemia]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Short stature]]
 * [[Petechia|Petechiae]] and [[Bruise|bruises]]
@@ Line 725: / Line 723: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Skeletal defects
-* Deafness
+* [[Deafness]]
-* VSD
+* [[Ventricular septal defect|VSD]]
-* Kidney abnormalities
+* [[Kidney]] abnormalities
-*
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pancytopenia]]
+* Hypercellular [[bone marrow]]
-*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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Progress to [[Acute myeloid leukemia|acute myelogenous leukemia]]
 * [[Neoplasm|Solid tumors]]
@@ Line 778: / Line 774: @@
 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
 |-
-! align="center" style="background:#DCDCDC;" |[[Aplastic anemia]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Unknown
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 787: / Line 783: @@
 | align="center" style="background:#F5F5F5;" + |±
 | align="center" style="background:#F5F5F5;" + |Biphasic (the young and the elderly)
-| align="center" style="background:#F5F5F5;" + |
+| 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pallor]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 796: / Line 792: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Shortness of breath]]
 *[[Fatigue]]
@@ Line 802: / Line 798: @@
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 *replacement of [[bone marrow]] by [[fat]]
@@ Line 813: / Line 809: @@
 | align="center" style="background:#F5F5F5;" + |[[Bone marrow examination]] +
 laboratory findings
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Fanconi anemia|Fanconi Anemia]]
 *[[Dyskeratosis congenita]]
@@ Line 819: / Line 815: @@
 *[[Preleukemia]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Paroxysmal nocturnal hemoglobinuria]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Deficiency of [[complement]] regulatory proteins
 *[[Mutation|Mutations]]
 | align="center" style="background:#F5F5F5;" + | +
@@ Line 831: / Line 826: @@
 | align="center" style="background:#F5F5F5;" + |Any age
 (usually younger adults)
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Sudden [[nocturnal]] [[hemoglobinuria]] with partial clearing during the day
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Normal
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 840: / Line 835: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Thrombosis]]
 *Smooth muscle [[dystonia]]
@@ Line 846: / Line 841: @@
 | align="center" style="background:#F5F5F5;" + |↓
 | align="center" style="background:#F5F5F5;" + |↓/Nl
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Pancytopenia]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Cellular [[Bone marrow|marrow]]
 *[[Erythroid]] [[hyperplasia]]
 *[[dyserythropoiesis]]
+* Hypocellular marrow in certain stages of the disease
-*Hypocellular marrow in certain stages of the disease
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Nl
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Hemoglobinuria]]
 | align="center" style="background:#F5F5F5;" + |[[Flow cytometry]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Chronic renal failure]]
 *[[Pulmonary hypertension]]
 *[[Aplastic anemia]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Disseminated intravascular coagulation]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Consumption
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 873: / Line 867: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Infection]]
 * [[Physical trauma|Trauma]]
@@ Line 879: / Line 873: @@
 * [[Cancer]]
 * [[Shock]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Acutely ill
 | align="center" style="background:#F5F5F5;" + | +
@@ Line 886: / Line 880: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + | +
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Shortness of breath]]
 *[[Fatigue]]
@@ Line 893: / Line 887: @@
 | align="center" style="background:#F5F5F5;" + |↓
 | align="center" style="background:#F5F5F5;" + |↓/Nl
-| 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Hemoglobinuria]]
 | align="center" style="background:#F5F5F5;" + |Lab findings
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * High mortality rate
 |-
-! align="center" style="background:#DCDCDC;" |Dyskeratosis congenital/telomere biology disorders
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Aberrant [[telomere]] biology
 * Germline [[Mutation|mutations]]
@@ Line 914: / Line 908: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare genetic disorder
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Isolated congenital nail dysplasia|Nail dysplasia]]
 * Abnormal [[Human skin color|skin pigmentation]]
@@ Line 924: / Line 918: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + | +
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Leukoplakia|Oral leukoplakia]]
 * [[Shortness of breath]]
@@ Line 931: / Line 925: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 939: / Line 933: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Clinical findings + genetic studies
-| align="center" style="background:#F5F5F5;" + |
+| 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]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Germline [[Mutation|mutations]]
 * [[Bone marrow suppression|Bone marrow failure]]
@@ Line 954: / Line 948: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare genetic disorder
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Skeletal abnormalities
 * [[Short stature]]
@@ Line 965: / Line 959: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + | +
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Steatorrhea]]
 * [[Delayed milestone|Growth retardation]]
@@ Line 971: / Line 965: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 979: / Line 973: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Clinical findings + genetic studies
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pancreatic insufficiency|Exocrine pancreatic insufficiency]]
 * [[Delayed milestone|Growth retardation]]
@@ Line 1,015: / Line 1,009: @@
 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
 |-
-! align="center" style="background:#DCDCDC;" |[[SLE]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Immune mediated [[Bone marrow suppression|bone marrow failure]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,024: / Line 1,018: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |More in young females
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Rash|Skin rash]]
 | align="center" style="background:#F5F5F5;" + | +
@@ Line 1,033: / Line 1,027: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + | +
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Weight loss]]
 * [[Oral ulcer|Mouth ulcers]]
@@ Line 1,041: / Line 1,035: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |↑
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Multi organ damage
 * Poor prognosis
 |-
-! align="center" style="background:#DCDCDC;" |[[Felty's syndrome|Felty syndrome]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Immune mediated [[Bone marrow suppression|bone marrow failure]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,064: / Line 1,058: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Rare [[autoimmune disease]], more in females 50-70 years old
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * History of [[rheumatoid arthritis]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Pallor]]
 * [[Hyperpigmentation|Skin hyperpigmentation]]
@@ Line 1,074: / Line 1,068: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + | +
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Painful, stiff, and swollen [[Joint|joints]]
 * [[Keratoconjunctivitis sicca]]
@@ Line 1,082: / Line 1,076: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,090: / Line 1,084: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Clinical findings + laboratory studies
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Rheumatoid arthritis]]
 * [[Infection|Infections]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Wiskott-Aldrich syndrome|Wiskott Aldrich syndrome]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Mutation in [[GATA1|GATA-1]]
 * Immune mediated [[bone marrow failure]]
@@ Line 1,104: / Line 1,098: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare [[Sex-linked|X-linked]] [[Recessive gene|recessive]] disease
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Immunodeficiency]]
 * Positive family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Eczema]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,114: / Line 1,108: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Dysentery|Bloody diarrhea]]
 | align="center" style="background:#F5F5F5;" + |↓
@@ Line 1,121: / Line 1,115: @@
 | align="center" style="background:#F5F5F5;" + |
 *[[Pancytopenia]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 *Small but low [[Platelet|platelets]]
@@ Line 1,128: / Line 1,122: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Genetic study
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Recurrent [[Infection|infections]]
 *[[Autoimmune disease|autoimmune disorders]]
 *[[Cancer|Malignancy]]
 |-
-! align="center" style="background:#DCDCDC;" |[[GATA2]] deficiency
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Immune mediated [[Bone marrow suppression|bone marrow failure]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,143: / Line 1,136: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Immunodeficiency]]
 * Positive family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Purpura]]
 *[[Petechia|Petechiae]]
@@ Line 1,158: / Line 1,151: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,166: / Line 1,159: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Genetic study
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Recurrent [[Infection|infections]]
 *[[Autoimmune disease|autoimmune disorders]]
 *[[Cancer|Malignancy]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Hemophagocytic lymphohistiocytosis]]
+! 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Immune mediated [[Bone marrow suppression|bone marrow failure]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,181: / Line 1,173: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Immunodeficiency]]
 * Positive family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Purpura]]
 *[[Petechia|Petechiae]]
@@ Line 1,196: / Line 1,188: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,204: / Line 1,196: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Genetic study
-| align="center" style="background:#F5F5F5;" + |
+| 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]]
+! 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]]
@@ Line 1,220: / Line 1,211: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Cirrhosis]]
 *[[Alcoholism|Alcohol use]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Purpura]]
 *[[Petechia|Petechiae]]
@@ Line 1,235: / Line 1,226: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |↑
@@ Line 1,243: / Line 1,234: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Clinical manifestation
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Portal vein thrombosis]]
 *[[Hepatorenal syndrome]]
@@ Line 1,250: / Line 1,241: @@
 *[[Spontaneous bacterial peritonitis]]
 |-
-! align="center" style="background:#DCDCDC;" |[[Glycogen storage disease|Storage diseases]] (eg, [[Gaucher's disease|Gaucher]])
+! 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]]
@@ Line 1,260: / Line 1,251: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |Rare in children
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Family history
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * [[Rash|Skin rash]]
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,273: / Line 1,264: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |
@@ Line 1,313: / Line 1,304: @@
 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Associated findings
 |-
-! align="center" style="background:#DCDCDC;" |[[Sepsis]]
+! 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]]
@@ Line 1,322: / Line 1,313: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Infection|Bacterial infection]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Petechiae]]
 *[[Purpura]]
@@ Line 1,334: / Line 1,325: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |±
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Malaise]]
 *[[Lymphadenopathy]]
@@ Line 1,340: / Line 1,331: @@
 | 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
@@ Line 1,348: / Line 1,339: @@
 Depends on the etiology
 | align="center" style="background:#F5F5F5;" + |Clinical manifestation + culture
-| align="center" style="background:#F5F5F5;" + |
+| 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]]
+! 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]]
@@ Line 1,361: / Line 1,352: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *High risk behaviors
 *Close contact
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Petechiae]]
 *[[Purpura]]
@@ Line 1,372: / Line 1,363: @@
 | align="center" style="background:#F5F5F5;" + |±
 | align="center" style="background:#F5F5F5;" + |±
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Lymphadenopathy]]
 *[[Muscle weakness]]
@@ Line 1,381: / Line 1,372: @@
 | 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;" + |
+| 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Hematuria]]
 | align="center" style="background:#F5F5F5;" + |Clinical manifestation + lab tests
-| align="center" style="background:#F5F5F5;" + |
+| 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]]
+! 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]]
@@ Line 1,404: / Line 1,395: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Malnutrition]]
 *[[Alcoholism|Alcohol use]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Normal
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,414: / Line 1,405: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Fatigue]]
 *[[Weakness]]
@@ Line 1,420: / Line 1,411: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,430: / Line 1,421: @@
 | align="center" style="background:#F5F5F5;" + |NA
 |-
-! align="center" style="background:#DCDCDC;" |Excessive [[alcohol]]
+! 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]]
@@ Line 1,439: / Line 1,430: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Alcoholism
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *History of [[Alcoholism|alcohol use]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Normal
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,448: / Line 1,439: @@
 | align="center" style="background:#F5F5F5;" + | +
 | 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="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Pancytopenia]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |↑
@@ Line 1,461: / Line 1,452: @@
 | align="center" style="background:#F5F5F5;" + |Nl
 | align="center" style="background:#F5F5F5;" + |Clinical manifestation
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Chronic liver disease]]
 |-
-! align="center" style="background:#DCDCDC;" |Other nutritional deficiency such as [[copper deficiency]], [[zinc]] toxicity
+! 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]]
@@ Line 1,473: / Line 1,464: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Malnutrition]]
 *[[Alcoholism|Alcohol use]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Normal
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,483: / Line 1,474: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Fatigue]]
 *[[Weakness]]
@@ Line 1,489: / Line 1,480: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,499: / Line 1,490: @@
 | align="center" style="background:#F5F5F5;" + |NA
 |-
-! align="center" style="background:#DCDCDC;" |[[Malnutrition]]
+! 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]]
@@ Line 1,508: / Line 1,499: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Any
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Malnutrition]]
 *[[Alcoholism|Alcohol use]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 * Normal
 | align="center" style="background:#F5F5F5;" + |−
@@ Line 1,518: / Line 1,509: @@
 | align="center" style="background:#F5F5F5;" + |−
 | align="center" style="background:#F5F5F5;" + |−
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Fatigue]]
 *[[Weakness]]
@@ Line 1,524: / Line 1,515: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 | align="center" style="background:#F5F5F5;" + |Nl
@@ Line 1,535: / Line 1,526: @@
 |-
 ! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Medications
-! align="left" style="background:#DCDCDC;" |Medications such as:
+! 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
@@ Line 1,546: / Line 1,537: @@
 | align="center" style="background:#F5F5F5;" + | +
 | align="center" style="background:#F5F5F5;" + |Patients with [[Cancer|malignancy]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Radiation therapy|Radiation]]
 *[[Cancer]]
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Purpura]]
 *[[Petechia|Petechiae]]
@@ Line 1,561: / Line 1,552: @@
 | 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;" + |
+| align="left" style="background:#F5F5F5;" + |
 *Hypocellular [[bone marrow]]
 *Megakaryocytic hypoplasia or aplasia
@@ Line 1,570: / Line 1,561: @@
 | align="center" style="background:#F5F5F5;" + |[[Hematuria case study one|Hematuria]]
 | align="center" style="background:#F5F5F5;" + |Clinical manifestation + exclusion of the other causes
-| align="center" style="background:#F5F5F5;" + |
+| align="left" style="background:#F5F5F5;" + |
 *[[Thrombosis]]
 |-