Causes of Thrombocytopenia
Thrombocytopenia can be caused by decreased platelet production, increased destruction, splenic sequestration, or dilution, with specific etiologies ranging from bone marrow disorders to autoimmune conditions and infections. 1, 2
Major Categories of Thrombocytopenia
Decreased Platelet Production
- Bone marrow disorders: Myelodysplastic syndromes, leukemias, other malignancies, and fibrosis impair megakaryocyte function 1, 2
- Aplastic anemia and megaloblastic anemia affect platelet production 1
- Inherited thrombocytopenias: Thrombocytopenia-absent radius (TAR) syndrome, Wiskott-Aldrich syndrome, MYH9-related disease, congenital amegakaryocytic thrombocytopenia, Bernard-Soulier syndrome, and type IIB von Willebrand disease 3, 1
- Viral infections can suppress bone marrow production of platelets 2
Increased Platelet Destruction
- Primary immune thrombocytopenia (ITP): Autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1, 2
- Secondary immune thrombocytopenia: Associated with:
- Heparin-induced thrombocytopenia (HIT): Typically presents with moderate thrombocytopenia 5-10 days after heparin initiation 2
- Thrombotic microangiopathies: Including thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome, and disseminated intravascular coagulation (DIC) 2, 5
- Post-transfusion purpura following recent blood transfusions 3
Splenic Sequestration
- Liver disease with portal hypertension and hypersplenism 3, 6
- Congestive splenomegaly from various causes 3
Other Causes
- Pregnancy-related: Gestational thrombocytopenia, preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) 2
- Dilutional thrombocytopenia: Following massive blood transfusion 5
- Pseudothrombocytopenia: EDTA-dependent platelet agglutination (laboratory artifact) 3, 4
- Cyanotic congenital heart disease: Can lead to decreased platelet count related to increased hematocrit levels 3
Diagnostic Approach
Initial Evaluation
- Confirm true thrombocytopenia by excluding pseudothrombocytopenia (collect blood in heparin or sodium citrate tube) 3, 4
- Evaluate peripheral blood smear to identify abnormalities inconsistent with ITP (such as schistocytes in TTP or leukocyte inclusion bodies in MYH9-related disease) 3
- Distinguish between isolated thrombocytopenia and pancytopenia through complete blood count with differential 1, 2
History and Physical Examination
- Assess for systemic diseases, infections, medication use, alcohol consumption, environmental toxin exposure 3, 1
- Check for recent vaccinations or transfusions 3
- Evaluate for constitutional symptoms (fever, weight loss), hepatomegaly, or lymphadenopathy that might indicate underlying disorders 3
- Note that moderate or massive splenomegaly suggests an alternative cause to ITP 3
Laboratory Testing
- Testing for HIV and hepatitis C is recommended in adults with suspected immune thrombocytopenia 1, 2
- Bone marrow examination may be necessary in:
Clinical Presentation
- Patients with platelet counts >50 × 10³/μL are generally asymptomatic 4
- Platelet counts between 20-50 × 10³/μL may present with mild skin manifestations (petechiae, purpura, ecchymosis) 4
- Platelet counts <10 × 10³/μL carry high risk of serious bleeding 4
- Some conditions (antiphospholipid syndrome, HIT, thrombotic microangiopathies) can paradoxically present with both bleeding and thrombosis 4, 7
Understanding the underlying cause of thrombocytopenia is essential for appropriate management and treatment decisions, as different etiologies require different therapeutic approaches 5, 7.