Causes of Thrombocytopenia (Low Platelet Count)
Thrombocytopenia can result from decreased platelet production, increased destruction, splenic sequestration, or dilution, with various underlying conditions affecting each of these mechanisms. 1, 2, 3
Major Categories of Thrombocytopenia
Decreased Platelet Production
- Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies can impair megakaryocyte function 1
- Aplastic anemia and megaloblastic anemia affect platelet production 3
- Inherited thrombocytopenias such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease 1, 3
- Viral infections can suppress bone marrow production of platelets 1
Increased Platelet Destruction
- Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1, 2
- Secondary immune thrombocytopenia associated with:
- Antiphospholipid syndrome 4
- Autoimmune disorders (e.g., systemic lupus erythematosus) 4
- Common variable immune deficiency 4
- Drug-induced thrombocytopenia 4, 2
- Infections (cytomegalovirus, Helicobacter pylori, hepatitis C, HIV, varicella zoster) 4, 1
- Lymphoproliferative disorders 4
- Bone marrow transplantation side effect 4
- Vaccination side effect 4
- Heparin-induced thrombocytopenia (HIT) - antibody-mediated reaction that can progress to thrombosis 5
- Thrombotic microangiopathies (TTP-HUS, DIC) 2, 6
Splenic Sequestration
Pregnancy-Associated Thrombocytopenia
- Gestational thrombocytopenia - most common cause in pregnancy 1
- Pregnancy-induced hypertension/preeclampsia 1
- HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) 1, 6
Clinical Presentation and Diagnostic Considerations
Clinical Manifestations Based on Platelet Count
50,000/μL: Generally asymptomatic 6
- 20,000-50,000/μL: May have mild skin manifestations (petechiae, purpura, ecchymosis) 6
- <10,000/μL: High risk of serious bleeding 6
Diagnostic Approach
- Initial evaluation should include a complete blood count with differential to identify isolated thrombocytopenia versus pancytopenia 1, 3
- Peripheral blood smear examination is essential to exclude pseudothrombocytopenia and identify abnormalities inconsistent with ITP 2, 3
- Patient history should focus on potential causes including systemic diseases, infections, medication use, alcohol consumption, and environmental toxin exposure 3
- Testing for HIV and hepatitis C should be considered in adults with suspected immune thrombocytopenia 1, 3
- Bone marrow examination may be necessary in selected cases, such as:
Important Red Flags
- Physical examination should be normal in primary ITP aside from bleeding manifestations 2
- The presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes of thrombocytopenia 2
- Constitutional symptoms such as fever and weight loss suggest underlying disorders like infection or malignancy 2
- Abrupt decrease in platelet count 1-2 weeks after surgery strongly suggests immunologic causes, including HIT 7
- Simultaneous thrombosis and thrombocytopenia should raise suspicion for HIT, antiphospholipid syndrome, or thrombotic microangiopathies 6
Management Considerations
- For primary ITP in children with no bleeding or mild bleeding, observation alone is recommended regardless of platelet count 1
- For patients requiring treatment, corticosteroids or IVIg are recommended as first-line options 1
- In HIT, promptly discontinue heparin if platelet count falls below 100,000/mm³ or if recurrent thrombosis develops 5
- For secondary ITP due to infections:
- Platelet transfusion is recommended for active hemorrhage or when platelet counts are less than 10,000/μL 6