Thrombocytopenia differential diagnosis
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farbod Zahedi Tajrishi, M.D.
Overview
Thrombocytopenia has a broad range of potential causes. While a good history and physical examination can be helpful to diagnose some of these causes such as drug-induced thrombocytopenia, they usually don't suffice and further evaluation is often needed. There are also some useful points that may guide the physician to an appropriate diagnosis. For example, asymptomatic, isolated thrombocytopenia most probably suggests ITP, while thrombocytopenia in critically ill, hospitalized patients is usually suggestive of iatrogenic causes (eg. dilution), platelet consumption, bone marrow suppression from infection/sepsis, or even drug-induced thrombocytopenia. One should consider however, that a wide variety of other conditions such as autoimmune disorders, nutrient deficiencies, thrombotic microangiopathies could all as well cause thrombocytopenia.
Thrombocytopenia Differential Diagnosis
Differentiating the diseases that can cause thrombocytopenia:
Category | Condition | Etiology | Mechanism | Inherited | Acquried | Clinical manifestations | Para−clinical findings | Gold standard | Associated findings | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Demography | History | Symptoms | Signs | ||||||||||||||||||||||||
Lab Findings | |||||||||||||||||||||||||||
Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other | CBC | PBS | Bone marrow exam | PT | PTT | UA | |||||||||||||||
Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Plt | HB | WBC | ||||||||||||||||||||||
Hematology | Bone marrow disorders | Myelodysplastic syndromes[1] |
|
+ | − | − | -/+ | + | Elderly | Exposure to | + | Petechiae, purpura, diffuse erythematous rash | + | Nl | + | + | Shortness of breath, fatigue | ↓ | ↓ | ↓ |
|
|
Nl | Nl | Nl | Bone marrow examination + clinical manifestation |
|
Aplastic anemia |
|
+ | − | − | -/+ | -/+ | Biphasic (the young and the elderly) |
Exposure to History of
|
− | − | + | Nl | − | − | Shortness of breath, fatigue, pallor | ↓ | ↓ | ↓ |
|
|
Bone marrow examination +
laboratory findings |
| |||||
Acute leukemia | + | AML in adults | +/- | + | +/- | ||||||||||||||||||||||
Paroxysmal nocturnal hemoglobinuria (PNH)[2] |
|
+ | + | - | − | + | Any age
(usually younger adults) |
Sudden nocturnal hemoglobinuria with partial clearing during the day | - | - | - | Nl | - | - |
|
↓/Nl | ↓ | ↓/Nl | Pancytopenia |
|
Nl | Nl | hemoglobinuria | Flow cytometry | |||
Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings | ||
Thrombotic microangiopathy (TMA) | Thrombotic thrombocytopenic purpura (TTP) | Deficiency of, or antibodies to, the metalloprotease ADAMTS13 | - | + | - | -/+ | + | Any age |
|
+ | +
(petechiae are common) |
Not common | Nl or ↑ | - | + |
|
↓ | ↓ | Nl
or ↑ |
Fragmented RBCs | NA | Nl | Nl | Hemoglobinuria | Laboratory findings |
| |
Hemolytic uremic syndrome (HUS) |
|
+ | -/+ | + | Children |
|
+ | - | - | + | ↓ | ↓ | Fragmented RBCs | NA | Nl | Nl | Laboratory findings |
| |||||||||
DIC | + | + | − | + | Any age | History of trauma, sepsis, malignancy, vasculitis or exogenous toxins | + | + | ↓ | Schistocytes | ↑↑ | ↑ | Laboratory findings | ||||||||||||||
Congenital platelet disorders[3][4] | MYH-9 related disorders | Cytoskeletal defects in megakaryocytes | + | − |
|
↓ |
|
||||||||||||||||||||
Bernard-Soulier syndrome | Absence of
Gp Ib-IX-V |
+ | − | − | + | − | Children | History of easy bruising and bleeding symptoms | − | − | + | Nl | − | − | − | ↓ | Nl | Nl | Large platelets | NA | Nl | Nl | Nl | Flow cytometry | Increased | ||
Gray platelet syndrome | + | − | |||||||||||||||||||||||||
Wiskott-Aldrich syndrome | Mutation in GATA-1 | + | − | Small platelets |
| ||||||||||||||||||||||
Thrombocytopenia with absent radius (TAR) syndrome | 1q21.1 deletion and bone marrow failure | + | − | Normal size platelets | |||||||||||||||||||||||
Alport syndrome | + | − | |||||||||||||||||||||||||
Von Willebrand disease | VWF deficiency/dysfunction | − | − | + | Rarely | More common with O blood type | Bleeding symptoms | − | − | + | − | − | − | − | Nl/ ↓ | Nl/↓ | Nl | Large platelets | Nl | Nl or ↑ | Laboratory findings | ||||||
Nutrient deficiencies | Folate, vitamin B12, copper | + | |||||||||||||||||||||||||
Category | Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings | |
Rheumatologic/autoimmune disorders | ITP[5] |
|
+ | + | − | − | + | Any age | − | − | Ecchymoses and | + Mucocutaneous | Nl | − | − | − | ↓↓↓ | Nl | Nl | Nl | Large platelets, otherwise normal | Nl | Nl | Nl | Diagnosis of exclusion |
| |
Systemic lupus erythematosus[6] |
|
- | + | - | - | + | Young women, more prevalent in Africans and Asians |
|
+ | Malar rash, generalized maculopapular rash, discoid rash | + | Nl or ↑ | + | + |
|
↓ | ↓ | ↓ | Pancytopenia | Pancytopenia | ↑ | ↑ |
|
Clinical manifestation + serology |
| ||
Antiphospholipid syndrome[7] |
|
- | + | - | + | + | Middle aged women, more in African American and Hispanic population |
|
- | - | - | Nl | - | - | ↓ | Nl | ↓ | Reduced platelets and WBC | Reduced platelets and WBC | Nl | ↑ | Clinical manifestation + repeated positive tests of aPL |
| ||||
Felty's syndrome[8] |
|
- | + | + | -/+ | + | Rare, young women | - |
|
- | Nl | + | - |
|
↓ | Nl | ↓ | Reduced platelets and WBC | Reduced platelets and WBC | Nl | Nl | Nl | Clinical manifestation |
| |||
Category | Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings | |
Infection-induced | Bacterial infections | Sepsis[9] |
|
+ | + | - | - | + | Any | + | -/+ | Nl to ↓ | - | -/+ | ↓/↑ | Nl | ↑↑ | ↑ | ↑ | +
Depends on the etiology |
Clinical manifestation + culture |
| |||||
Helicobacter pylori |
|
+ | |||||||||||||||||||||||||
Tick-borne infection | + | ||||||||||||||||||||||||||
Viral infections | HIV |
|
+ | + | + | ||||||||||||||||||||||
Other viruses such as rubella, mumps, varicella, parvovirus, hepatitis C, & Epstein-Barr virus | + | ||||||||||||||||||||||||||
Parasitic infections | Malaria | ||||||||||||||||||||||||||
Babesiosis | |||||||||||||||||||||||||||
Category | Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings | |
Medication/toxicity | Antibiotics/ |
|
+ | + | - | - | + | Any |
|
- | - | Nl | - | - | - | ↓↓ | ↓ | Nl | Reduced platelets | NA | Nl | Nl | Nl | Clinical manifestation + exclusion of the other causes | NA | ||
Heparin-induced thrombocytopenia[11] |
|
- | + | - | - | + | Any |
|
- |
|
- | Nl | - | - | - | ↓ | Nl | Nl | Reduced platelets | NA | Nl | Nl | Nl | ELISA |
| ||
Cytotoxic chemotherapy[12] | + | - | - | - | + | Patients with malignancy |
|
- |
|
- | Nl | - | - | - | ↓ | ↓ | ↓ | Reduced platelets | Megakaryocytic hypoplasia or aplasia | ↑ | ↑ | Hematuria | Clinical manifestation + exclusion of the other causes | ||||
Radiation therapy[13] |
|
+ | - | - | - | + | Patients with malignancy | - | + | Nl | - | - | - | ↓ | ↓ | ↓ | Reduced platelets | Megakaryocytic hypoplasia or aplasia | ↑ | ↑ | Hematuria | Clinical manifestation + exclusion of the other causes | |||||
GI | Chronic liver disease[14] | + | - | - | - | + | Any | - | + | ↓ | + | + | - | ↓ | ↓ | Nl | Reduced platelets | NA | ↑ | ↑ | Nl | Biopsy |
| ||||
Portal hypertension[15] | + | - | - | - | + | Any | - | + | ↓ | + | + | - | ↓ | ↓ | Nl | Reduced platelets | NA | ↑ | ↑ | Nl | Clinical manifestation | ||||||
Category | Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings | |
Vascular | Giant capillary hemangioma (Kasabach-Merritt syndrome)[16][17] |
|
− | + | − | + | − | Infants |
|
− |
|
Intralesional bleeding | Nl | − | − | Visceral hemangiomas | ↓↓ | ↓↓ | Nl | Normocytic normochromic erythrocytes and markedly reduced platelets | Normal erythropoiesis, myelopoiesis, and megakaryocytic hyperplasia | ↑ | ↑ | Hematuria | Biopsy |
| |
Cardiopulmonary bypass[18] |
|
− | + | − | − | + | Elderly | − | + | Nl or ↑ | - | - | - | ↓ | ↓ | Nl | Normocytic normochromic erythrocytes and markedly reduced platelets | NA | ↑ | ↑ | Hematuria | Clinical manifestation | |||||
Other | Alcohol[19] |
|
+ | − | + | − | + | Any |
|
− | − | - | Nl | + | + | ↓ | ↓ | ↓ | Cytopenia, macrocytosis | Cytopenia, macrocytosis | ↑ | ↑ | Nl | Clinical manifestation | |||
Post-transfusion purpura[20][21] |
|
− | + | − | − | + | Women |
|
− | + | ↓ | − | − | − | ↓↓↓ | ↓ | Nl | Nl | NA | Nl | Nl | Nl | Positive circulating alloantibody to a common platelet antigen |
| |||
Gestational thrombocytopenia[22] |
|
− | − | − | − | + | Pregnant women |
|
− | − | − | Nl | − | − | − | ↓ | Nl | Nl | Nl | NA | Nl | Nl | Nl | Diagnosis of exclusion |
| ||
HELLP syndrome[23][24] |
|
− | + | − | − | + | Pregnant > 25 years |
|
− | − | + | ↑ | − | + | ↓ | ↓ | Nl | Schistocytes | NA | Nl | Nl | Proteinuria | Lab abnormalities |
| |||
Idiopathic cyclic thrombocytopenia[25] |
|
+ | + | - | - | + | Females with the median age of onset 35 years |
|
- | Minor mucocutaneous bleeding | Nl | - | - | - | ↓ | Nl | Nl | Reduced platelets and megakaryocytes | Megakaryocytic hypoplasia or aplasia | Nl | Nl | Nl | Diagnosis of exclusion | ||||
Pseudothrombocytopenia[26] | - | - | - | - | + | Rare | Collected sample in EDTA anticoagulant | - | - | - | Nl | - | - | - | ↓ | Nl | Nl | Low platelet count and platelet clumps | Low platelet count and platelet clumps | Nl | Nl | Nl | Repeat collecting sample in a heparin tube | Nl | |||
Category | Condition | Etiology | Decreased platelet production | Platelet destruction in blood | Platelet destruction in spleen | Inherited | Acquried | Demography | History | Fever | Rash | Bleeding | BP | Splenomegaly | Jaundice | Other signs | Plt | HB | WBC | PBS | Bone marrow exam | PT | PTT | UA | Gold standard | Associated findings |
References
- ↑ Natelson, Ethan A.; Pyatt, David (2013). "Acquired Myelodysplasia or Myelodysplastic Syndrome: Clearing the Fog". Advances in Hematology. 2013: 1–11. doi:10.1155/2013/309637. ISSN 1687-9104.
- ↑ Brodsky RA (2014). "Paroxysmal nocturnal hemoglobinuria". Blood. 124 (18): 2804–11. doi:10.1182/blood-2014-02-522128. PMC 4215311. PMID 25237200.
- ↑ Nurden AT, Freson K, Seligsohn U (2012). "Inherited platelet disorders". Haemophilia. 18 Suppl 4: 154–60. doi:10.1111/j.1365-2516.2012.02856.x. PMID 22726100.
- ↑ D'Andrea G, Chetta M, Margaglione M (2009). "Inherited platelet disorders: thrombocytopenias and thrombocytopathies". Blood Transfus. 7 (4): 278–92. doi:10.2450/2009.0078-08. PMC 2782805. PMID 20011639.
- ↑ Zufferey, Anne; Kapur, Rick; Semple, John (2017). "Pathogenesis and Therapeutic Mechanisms in Immune Thrombocytopenia (ITP)". Journal of Clinical Medicine. 6 (2): 16. doi:10.3390/jcm6020016. ISSN 2077-0383.
- ↑ Abu-Hishmeh M, Sattar A, Zarlasht F, Ramadan M, Abdel-Rahman A, Hinson S, Hwang C (October 2016). "Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature". Am J Case Rep. 17: 782–787. PMC 5083062. PMID 27777394.
- ↑ Artim-Esen, Bahar; Diz-Küçükkaya, Reyhan; İnanç, Murat (2015). "The Significance and Management of Thrombocytopenia in Antiphospholipid Syndrome". Current Rheumatology Reports. 17 (3). doi:10.1007/s11926-014-0494-8. ISSN 1523-3774.
- ↑ Chavalitdhamrong, Disaya; Molovic-Kokovic, Ana; Iliev, Andrey (2009). "Felty's Syndrome as an initial presentation of Rheumatoid Arthritis: a case report". Cases Journal. 2 (1): 206. doi:10.1186/1757-1626-2-206. ISSN 1757-1626.
- ↑ Wu, Qin; Ren, Jianan; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Liu, Song; Wu, Yin; Hu, Dong; Zhao, Yunzhao; Li, Jieshou (2014). "Recombinant human thrombopoietin improves platelet counts and reduces platelet transfusion possibility among patients with severe sepsis and thrombocytopenia: A prospective study". Journal of Critical Care. 29 (3): 362–366. doi:10.1016/j.jcrc.2013.11.023. ISSN 0883-9441.
- ↑ Visentin GP, Liu CY (August 2007). "Drug-induced thrombocytopenia". Hematol. Oncol. Clin. North Am. 21 (4): 685–96, vi. doi:10.1016/j.hoc.2007.06.005. PMC 1993236. PMID 17666285.
- ↑ Lovecchio, F. (2014). "Heparin-induced thrombocytopenia". Clinical Toxicology. 52 (6): 579–583. doi:10.3109/15563650.2014.917181. ISSN 1556-3650.
- ↑ Parameswaran, R.; Lunning, M.; Mantha, S.; Devlin, S.; Hamilton, A.; Schwartz, G.; Soff, G. (2014). "Romiplostim for management of chemotherapy-induced thrombocytopenia". Supportive Care in Cancer. 22 (5): 1217–1222. doi:10.1007/s00520-013-2074-2. ISSN 0941-4355.
- ↑ Bercovitz RS, Josephson CD (2012). "Thrombocytopenia and bleeding in pediatric oncology patients". Hematology Am Soc Hematol Educ Program. 2012: 499–505. doi:10.1182/asheducation-2012.1.499. PMID 23233625.
- ↑ Loffredo, Lorenzo; Violi, Francesco (2018). "Thrombopoietin receptor agonists and risk of portal vein thrombosis in patients with liver disease and thrombocytopenia: A meta-analysis". Digestive and Liver Disease. doi:10.1016/j.dld.2018.06.005. ISSN 1590-8658.
- ↑ Jia YP, Lu Q, Gong S, Ma BY, Wen XR, Peng YL, Lin L, Chen HY, Qiu L, Luo Y (September 2007). "Postoperative complications in patients with portal vein thrombosis after liver transplantation: evaluation with Doppler ultrasonography". World J. Gastroenterol. 13 (34): 4636–40. PMC 4611842. PMID 17729421.
- ↑ Lewis D, Vaidya R. Kasabach Merritt Syndrome. [Updated 2018 Jul 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www-ncbi-nlm-nih-gov.ezp-prod1.hul.harvard.edu/books/NBK519053/
- ↑ Vinod, Kolar Vishwanath; Johny, Joseph; Vadivelan, Mehalingam; Hamide, Abdoul (2017). "Kasabach-Merritt Syndrome in an adult". Turkish Journal of Hematology. doi:10.4274/tjh.2017.0429. ISSN 1300-7777.
- ↑ Ji, Sung-Mi; Kim, Sung-Hoon; Nam, Jae-Sik; Yun, Hye-Joo; Choi, Jeong-Hyun; Lee, Eun-Ho; Choi, In-Cheol (2015). "Predictive value of rotational thromboelastometry during cardiopulmonary bypass for thrombocytopenia and hypofibrinogenemia after weaning of cardiopulmonary bypass". Korean Journal of Anesthesiology. 68 (3): 241. doi:10.4097/kjae.2015.68.3.241. ISSN 2005-6419.
- ↑ Latvala J, Parkkila S, Niemelä O (April 2004). "Excess alcohol consumption is common in patients with cytopenia: studies in blood and bone marrow cells". Alcohol. Clin. Exp. Res. 28 (4): 619–24. PMID 15100613.
- ↑ McCrae, Keith R.; Herman, Jay H. (1996). "Posttransfusion purpura: Two unusual cases and a literature review". American Journal of Hematology. 52 (3): 205–211. doi:10.1002/(SICI)1096-8652(199607)52:3<205::AID-AJH13>3.0.CO;2-E. ISSN 0361-8609.
- ↑ Pavenski, Katerina; Webert, Kathryn E.; Goldman, Mindy (2008). "Consequences of transfusion of platelet antibody: a case report and literature review". Transfusion. 48 (9): 1981–1989. doi:10.1111/j.1537-2995.2008.01796.x. ISSN 0041-1132.
- ↑ Reese, Jessica A.; Peck, Jennifer D.; Deschamps, David R.; McIntosh, Jennifer J.; Knudtson, Eric J.; Terrell, Deirdra R.; Vesely, Sara K.; George, James N. (2018). "Platelet Counts during Pregnancy". New England Journal of Medicine. 379 (1): 32–43. doi:10.1056/NEJMoa1802897. ISSN 0028-4793.
- ↑ Barnhart, Lynette (2015). "HELLP Syndrome and the Effects on the Neonate". Neonatal Network. 34 (5): 269–273. doi:10.1891/0730-0832.34.5.269. ISSN 0730-0832.
- ↑ Haram, Kjell; Svendsen, Einar; Abildgaard, Ulrich (2009). "The HELLP syndrome: Clinical issues and management. A Review". BMC Pregnancy and Childbirth. 9 (1). doi:10.1186/1471-2393-9-8. ISSN 1471-2393.
- ↑ Go, Ronald S. (2005). "Idiopathic cyclic thrombocytopenia". Blood Reviews. 19 (1): 53–59. doi:10.1016/j.blre.2004.05.001. ISSN 0268-960X.
- ↑ Tan, Geok Chin; Stalling, Melissa; Dennis, Gretchen; Nunez, Maria; Kahwash, Samir B. (2016). "Pseudothrombocytopenia due to Platelet Clumping: A Case Report and Brief Review of the Literature". Case Reports in Hematology. 2016: 1–4. doi:10.1155/2016/3036476. ISSN 2090-6560.