Thrombocytosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Overview

Thrombocytosis Differential Diagnosis

Differentiating the diseases that can cause Thrombocytosis :

Category Condition Etiology Mechanism Inherited Acquried Clinical manifestations Para−clinical findings Gold standard Associated findings
Demography History Symptoms Signs
Lab Findings Imaging
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 NA Bone marrow examination + clinical manifestation
Aplastic anemia Acquired:

Inherited:

  • Unknown
+ - - -/+ -/+ Biphasic (the young and the elderly)

Exposure to

History of

- - + Nl - - Shortness of breath, fatigue, pallor NA Bone marrow examination +

laboratory findings

Inherited forms are associated with:
Acute leukemia +
Paroxysmal nocturnal hemoglobinuria (PNH)[2]
  • Mutations
+ - + Any age

(usually younger adults)

↓/Nl ↓/Nl
  • The marrow may also become hypocellular or even aplastic in certain stages of the disease
Nl Nl hemoglobinuria NA Flow cytometry
Thrombotic microangiopathy (TMA) Thrombotic thrombocytopenic purpura (TTP) Deficiency of, or antibodies to, the metalloprotease ADAMTS13   + -/+ + Any age + Fragmented RBCs Nl Nl
Hemolytic uremic syndrome (HUS) + -/+ + Children Nl Nl
DIC + - + ↑↑
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 NA 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 Imaging Gold standard Associated findings
Rheumatologic/autoimmune disorders ITP
  • Immune-mediated platelet destruction
  • Inhibition of platelet release from the megakaryocyte  
+ + - - + Any age - - Ecchymoses and

petechia

+ Mucocutaneous Nl - - - ↓↓↓ Nl Nl Nl Large platelets, otherwise normal Nl Nl Nl NA Diagnosis of exclusion Spontaneous remission  
Systemic lupus erythematosus (SLE) +
Antiphospholipid syndrome (APS) Autoantibody-mediated syndrome +
Felty's syndrome Splenomegaly +
Infection-induced Bacterial infections Sepsis Direct bone marrow suppression + +
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 Imaging Gold standard Associated findings
Medication/toxicity Antibiotics/

Antiepileptic

Occurrence of drug-dependent, platelet-reactive antibodies + +
Heparin-induced thrombocytopenia Anti-heparin/PF4 antibody  + ELISA Early or delayed-onset
Cytotoxic chemotherapy +
Radiation therapy Predictable, dose-dependent myelosuppression +
OTC agents Quinine-containing beverages
GI Chronic liver disease + + + ↓↓
Portal hypertension
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 Imaging Gold standard Associated findings
Vascular Giant capillary hemangioma (Kasabach-Merritt syndrome) Platelet destruction +
Aortic aneurysm Platelet destruction +
Cardiopulmonary bypass Platelet destruction - + - - +
Other Alcohol[5] Platelet production suppression + - + - + Any - - - Nl + + Cytopenia, macrocytosis Cytopenia, macrocytosis Nl NA Clinical manifestation
Post-transfusion purpura[6][7] Platelet destruction by anti-platelet antibodies - + - - + Women - Purpura, petechiae + - - - ↓↓↓ Nl Nl NA Nl Nl Nl NA Positive circulating alloantibody to a common platelet antigen
  • Severe but rare reaction
Gestational thrombocytopenia[8] Might be physiologic adaptation of pregnancy - - - - + Pregnant women
  • Positive history of mild thrombocytopenia
- - - Nl - - - Nl Nl Nl NA Nl Nl Nl NA Diagnosis of exclusion
  • Self-limited condition
HELLP syndrome[9][10] Unknown - + - - + Pregnant > 25 years - - + - + Nl NA Nl Nl Proteinuria NA Lab abnormalities
Idiopathic cyclic thrombocytopenia[11] Unknown
Pseudothrombocytopenia

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. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Go, Ronald S. (2005). "Idiopathic cyclic thrombocytopenia". Blood Reviews. 19 (1): 53–59. doi:10.1016/j.blre.2004.05.001. ISSN 0268-960X.