What are the causes of thrombocytopenia?

Causes of Thrombocytopenia

Thrombocytopenia is primarily caused by decreased platelet production, increased destruction, splenic sequestration, or dilution, with specific etiologies including immune-mediated disorders, bone marrow diseases, infections, medications, and inherited conditions. 1, 2

Major Categories of Thrombocytopenia

Decreased Platelet Production

• Bone marrow disorders including myelodysplastic syndromes, leukemias, other malignancies, and fibrosis can impair megakaryocyte function 3, 1
• Aplastic anemia and megaloblastic anemia affect platelet production 3
• Viral infections can suppress bone marrow production of platelets 1
• Inherited thrombocytopenias such as thrombocytopenia-absent radius (TAR) syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease 3, 1

Increased Platelet Destruction

• Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1, 4
• Secondary immune thrombocytopenia associated with:
  • Autoimmune disorders (including systemic lupus erythematosus) 3, 5
  • Infections (HIV, hepatitis C, Helicobacter pylori) 3, 5
  • Lymphoproliferative disorders 3, 1
  • Recent vaccinations 3, 5
• Drug-induced thrombocytopenia (prescription or non-prescription medications) 3, 2
• Thrombotic microangiopathies (TTP-HUS) 4, 6
• Disseminated intravascular coagulation (DIC) 1, 7
• Heparin-induced thrombocytopenia (HIT) 1, 6

Splenic Sequestration

• Liver disease including alcoholic liver cirrhosis 3, 7
• Portal hypertension 5

Other Causes

• Pregnancy-related:
  • Gestational thrombocytopenia 1
  • Preeclampsia and HELLP syndrome 1
• Antiphospholipid syndrome 1, 2
• Recent transfusions (posttransfusion purpura) 3
• Pseudothrombocytopenia due to EDTA-dependent platelet agglutination 3, 4

Diagnostic Approach for Thrombocytopenia

Initial Evaluation

• Complete blood count with differential to identify isolated thrombocytopenia versus pancytopenia 1, 4
• Peripheral blood smear examination by a qualified hematologist or pathologist to exclude pseudothrombocytopenia and identify abnormalities inconsistent with ITP (such as schistocytes or leukocyte inclusion bodies) 3, 1
• Patient history to identify potential causes:
  • Systemic diseases and infections
  • Medication use
  • Alcohol consumption
  • Environmental toxin exposure
  • Recent vaccinations or transfusions 3, 4

Physical Examination

• Look for bleeding manifestations 3
• Assess for splenomegaly (moderate or massive splenomegaly suggests alternative causes) 3
• Check for constitutional symptoms (fever, weight loss), hepatomegaly, or lymphadenopathy that might indicate underlying disorders like HIV, SLE, or lymphoproliferative disease 3, 4

Additional Testing

• Testing for HIV and hepatitis C in adults with suspected immune thrombocytopenia 1, 4
• Bone marrow examination in selected cases:
  • Patients older than 60 years
  • Those with systemic symptoms or abnormal signs
  • Cases where splenectomy is considered 3, 1

Clinical Considerations

• Patients with platelet counts >50 × 10³/μL are generally asymptomatic 2
• Patients with platelet counts between 20-50 × 10³/μL may have mild skin manifestations (petechiae, purpura, ecchymosis) 2
• Patients with platelet counts <10 × 10³/μL have high risk of serious bleeding 2
• Some conditions can present with both bleeding and thrombosis (antiphospholipid syndrome, heparin-induced thrombocytopenia, thrombotic microangiopathies) 2, 8
• Response to ITP-specific therapy (e.g., intravenous immunoglobulin) supports but does not confirm the diagnosis of ITP 3