Thrombocytopenia differential diagnosis: Difference between revisions

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| align="center" style="background:#F5F5F5;" + |AML in adults
| align="center" style="background:#F5F5F5;" + |AML in adults
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |+/-
| align="center" style="background:#F5F5F5;" + | +/-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |+
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |+/-
| align="center" style="background:#F5F5F5;" + | +/-
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* Mutations  
* Mutations  
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| align="center" style="background:#F5F5F5;" + |+
| align="center" style="background:#F5F5F5;" + |
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| align="center" style="background:#F5F5F5;" + | −
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(usually younger adults)
(usually younger adults)
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Sudden [[nocturnal]] [[hemoglobinuria]] with partial clearing during the day
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |-
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
* [[thrombosis]]
* [[thrombosis]]
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! rowspan="3" align="center" style="background:#DCDCDC;" + |Thrombotic microangiopathy (TMA)
! rowspan="3" align="center" style="background:#DCDCDC;" + |Thrombotic microangiopathy (TMA)
! align="center" style="background:#DCDCDC;" + |[[Thrombotic thrombocytopenic purpura]] ([[Thrombotic thrombocytopenic purpura|TTP]])
! align="center" style="background:#DCDCDC;" + |[[Thrombotic thrombocytopenic purpura]] ([[Thrombotic thrombocytopenic purpura|TTP]])
| align="center" style="background:#F5F5F5;" + |Deficiency of, or antibodies to, the metalloprotease ADAMTS13  
| align="center" style="background:#F5F5F5;" + |Deficiency of, or antibodies to, the metalloprotease [[ADAMTS13]]  
| align="center" style="background:#F5F5F5;" + |  
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + | -/+
| align="center" style="background:#F5F5F5;" + | -/+
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |Any age
| align="center" style="background:#F5F5F5;" + |Any age
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
* Neurologic manifestations
* Fatigue may accompany the anemia
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + | +
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |+
| align="center" style="background:#F5F5F5;" + |
 
| align="center" style="background:#F5F5F5;" + |
([[Petechia|petechiae]] are common)
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Not common
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl or ↑
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + | -
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Signs of renal impairment
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |↓
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Nl
 
or ↑
| align="center" style="background:#F5F5F5;" + |Fragmented [[Red blood cell|RBC]]<nowiki/>s
| align="center" style="background:#F5F5F5;" + |Fragmented [[Red blood cell|RBC]]<nowiki/>s
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |NA
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |Nl
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |[[Hemoglobinuria]]
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |Laboratory findings
| align="center" style="background:#F5F5F5;" + |
| align="center" style="background:#F5F5F5;" + |
* [[Hemolysis]]
* [[Hemolysis]]

Revision as of 21:24, 31 August 2018

Thrombocytopenia Microchapters

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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]
  • Unknown
  • Mutation
+ -/+ + 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]
  • Mutations
+ + + Any age

(usually younger adults)

Sudden nocturnal hemoglobinuria with partial clearing during the day - - - Nl - - ↓/Nl ↓/Nl
  • The marrow may also become hypocellular or even aplastic in certain stages of the disease
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
  • Neurologic manifestations
  • Fatigue may accompany the anemia
+ +

(petechiae are common)

Not common Nl or ↑ - Nl Signs of renal impairment Nl

or ↑

Fragmented RBCs NA Nl Nl Hemoglobinuria Laboratory findings
Hemolytic uremic syndrome (HUS) + -/+ + Children Nl Nl
DIC + + + Any age History of trauma, sepsis, malignancy, vasculitis or exogenous toxins + + Schistocytes ↑↑ Laboratory studies including CBC, PT, PTT, FDP and d-dimer
Congenital platelet disorders[3][4] MYH-9 related disorders Cytoskeletal defects in megakaryocytes +
  • Leukocyte inclusions
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

bleeding time

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

petechia

+ Mucocutaneous Nl ↓↓↓ Nl Nl Nl Large platelets, otherwise normal Nl Nl Nl Diagnosis of exclusion
  • Spontaneous remission  
Systemic lupus erythematosus[6] - + - - + Young women, more prevalent in Africans and Asians + Malar rash, generalized maculopapular rash, discoid rash +

Hemoptysis

Nl or ↑ + + Pancytopenia Pancytopenia Clinical manifestation + serology
Antiphospholipid syndrome[7]
  • Autoantibody-mediated syndrome
- + - + + 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 + -
  • Lymphadenopathy
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
  • Associated with ↑ mortality
Helicobacter pylori
  • Immune thrombocytopenia
+
Tick-borne infection +
Viral infections HIV
  • An ITP-like condition called primary HIV-associated thrombocytopenia
+ + +
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/

Antiepileptic[10]

  • Occurrence of drug-dependent, platelet-reactive antibodies
+ + - - + Any
  • Drug ingestion or injection
- - Nl - - - ↓↓ Nl Reduced platelets NA Nl Nl Nl Clinical manifestation + exclusion of the other causes NA
Heparin-induced thrombocytopenia[11]
  • Anti-heparin/PF4 antibody 
- + - - + Any
  • Heparin injection
-
  • Necrotic skin lesions
- Nl - - - Nl Nl Reduced platelets NA Nl Nl Nl ELISA
Cytotoxic chemotherapy[12] + - - - + Patients with malignancy
  • Drug ingestion or injection
  • Cancer
- - 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
  • Kaposiform hemangioendothelioma
  • Tufted angioma
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
  • Severe but rare reaction
Gestational thrombocytopenia[22]
  • Might be physiologic adaptation of pregnancy
+ Pregnant women
  • Positive history of mild thrombocytopenia
Nl Nl Nl Nl NA Nl Nl Nl Diagnosis of exclusion
  • Self-limited condition
HELLP syndrome[23][24]
  • Unknown
+ + Pregnant > 25 years + + Nl Schistocytes NA Nl Nl Proteinuria Lab abnormalities
Idiopathic cyclic thrombocytopenia[25] + + - - + Females with the median age of onset 35 years
  • Misdiagnosed as ITP with uniformly poor responses
- 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

  1. 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.
  2. Brodsky RA (2014). "Paroxysmal nocturnal hemoglobinuria". Blood. 124 (18): 2804–11. doi:10.1182/blood-2014-02-522128. PMC 4215311. PMID 25237200.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Lovecchio, F. (2014). "Heparin-induced thrombocytopenia". Clinical Toxicology. 52 (6): 579–583. doi:10.3109/15563650.2014.917181. ISSN 1556-3650.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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/
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. Go, Ronald S. (2005). "Idiopathic cyclic thrombocytopenia". Blood Reviews. 19 (1): 53–59. doi:10.1016/j.blre.2004.05.001. ISSN 0268-960X.
  26. 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.