Causes of Thrombocytopenia (Low Platelet Count)
Thrombocytopenia is caused by decreased platelet production, increased platelet destruction, splenic sequestration, or dilution, with immune-mediated destruction and bone marrow disorders being the most common etiologies. 1
Major Categories of Thrombocytopenia
Decreased Platelet Production
- Bone marrow disorders including myelodysplastic syndromes, leukemias, and other malignancies can impair megakaryocyte function 2, 1
- Inherited thrombocytopenias such as thrombocytopenia-absent radius (TAR) syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, Bernard-Soulier syndrome, and type IIB von Willebrand disease 2
- Megaloblastic anemia and aplastic anemia affect bone marrow production of platelets 2
- Viral infections can suppress bone marrow production 1
Increased Platelet Destruction
- Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 2, 1
- Secondary immune thrombocytopenia associated with:
- Drug-induced thrombocytopenia (numerous medications including heparin) 2, 3
- Thrombotic microangiopathies (TTP-HUS) 1, 3
- Post-transfusion purpura 2
Splenic Sequestration
- Liver disease and cirrhosis lead to hypersplenism and platelet sequestration 2, 3
- Portal hypertension causes increased splenic blood flow and platelet pooling 4
Other Causes
- Dilutional thrombocytopenia from massive transfusion 3
- Pregnancy-related thrombocytopenia including HELLP syndrome 3
- Disseminated intravascular coagulation (DIC) 5
- Pseudothrombocytopenia due to EDTA-dependent platelet agglutination (laboratory artifact) 2, 3
Clinical Presentation and Severity
- Platelet counts >50,000/μL: Generally asymptomatic 3
- Platelet counts 20,000-50,000/μL: May present with mild skin manifestations (petechiae, purpura, ecchymosis) 3
- Platelet counts <10,000/μL: High risk of serious bleeding 3
Diagnostic Approach
Initial Evaluation
- Confirm true thrombocytopenia by examining peripheral blood smear to exclude pseudothrombocytopenia 1
- Complete blood count with differential to identify isolated thrombocytopenia versus pancytopenia 2, 1
- Review medication history for potential drug-induced causes 2
Further Testing Based on Clinical Context
- Testing for HIV and hepatitis C in adults with typical ITP 1
- Bone marrow examination in selected cases:
- Testing for H. pylori infection in adults with ITP where clinically relevant 2
- Antinuclear antibody testing when autoimmune disease is suspected 2
Important Clinical Considerations
- Physical examination should be normal in primary ITP aside from bleeding manifestations 2
- Splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes rather than primary ITP 2, 1
- Constitutional symptoms like fever and weight loss suggest underlying disorders such as infection or malignancy 2
- Recent vaccinations may trigger immune thrombocytopenia 2
- Certain medications used to treat thrombocytopenia, such as prednisone, are indicated for idiopathic thrombocytopenic purpura 6
- Rituximab may cause prolonged hypogammaglobulinemia in some patients treated for immune thrombocytopenia 7
Treatment Considerations
- For primary ITP in children with no bleeding or mild bleeding, observation alone is recommended regardless of platelet count 2
- For pediatric patients requiring treatment, a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids is recommended as first-line treatment 2
- Platelet transfusion is indicated for active hemorrhage or when platelet counts are <10,000/μL 3
- Treatment should target the underlying cause when identified 5