What are the causes of thrombocytopenia (low platelet count)?

Causes of Thrombocytopenia (Low Platelet Count)

Thrombocytopenia can be caused by myriad conditions including systemic disease, infection, drugs, and primary hematologic disorders, requiring a systematic approach to diagnosis and management. 1

Major Categories of Thrombocytopenia

1. Decreased Platelet Production

• Bone marrow diseases including myelodysplastic syndromes, leukemias, other malignancies, fibrosis, aplastic anemia, and megaloblastic anemia 1
• Inherited thrombocytopenias: thrombocytopenia-absent radius (TAR) syndrome, radioulnar synostosis, congenital amegakaryocytic thrombocytopenia, Wiskott-Aldrich syndrome, MYH9-related disease, Bernard-Soulier syndrome, type IIB von Willebrand disease 1

2. Increased Platelet Destruction

• Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1
• Secondary immune thrombocytopenia associated with:
  • Autoimmune disorders (including systemic lupus erythematosus, antiphospholipid antibody syndrome) 1, 2
  • Infections (HIV, HCV, other viral infections) 1
  • Lymphoproliferative disorders 1
• Drug-induced thrombocytopenia from:
  • Cinchona alkaloid derivatives (quinine, quinidine) 3
  • Heparin (heparin-induced thrombocytopenia) 2
  • Sulfonamides, NSAIDs, anticonvulsants 3
  • Disease-modifying antirheumatic drugs and diuretics 3
• Thrombotic microangiopathies (TTP-HUS) 1, 2
• Disseminated intravascular coagulation (DIC) 4

3. Splenic Sequestration

• Liver disease including alcoholic liver cirrhosis 1, 2
• Hypersplenism from any cause 4

4. Other Causes

• Pregnancy-related conditions (including HELLP syndrome) 2
• Recent transfusions (possibility of posttransfusion purpura) 1
• Recent vaccinations 1
• Alcohol abuse 1
• Consumption of quinine (tonic water) 1
• Exposure to environmental toxins 1
• Dilutional thrombocytopenia (massive transfusion) 2, 5
• Pseudothrombocytopenia (laboratory artifact) - EDTA-dependent platelet agglutination 1, 3

Clinical Presentation and Severity

• Platelet count >50 × 10³/μL: Generally asymptomatic 2
• Platelet count 20-50 × 10³/μL: May have mild skin manifestations (petechiae, purpura, ecchymosis) 2
• Platelet count <10 × 10³/μL: High risk of serious bleeding 2

Diagnostic Approach

Initial Evaluation

• Confirm true thrombocytopenia by examining peripheral blood smear to exclude pseudothrombocytopenia 1
• Review previous platelet counts to distinguish acute from chronic thrombocytopenia 2
• Evaluate for isolated thrombocytopenia versus associated abnormalities in other cell lines 1

Key Diagnostic Tests

• Complete blood count and peripheral blood smear examination 1, 5
• If anemia is present, reticulocyte count to determine if due to blood loss or decreased production 1
• Testing for HIV and HCV in adults with typical ITP 1
• Helicobacter pylori testing in adults where clinically relevant 1
• Bone marrow examination in selected cases:
  • Patients older than 60 years 1
  • Those with systemic symptoms or abnormal signs 1
  • Before splenectomy in certain cases 1
  • Not necessary in children with typical ITP features 1

Important Clinical Considerations

• Physical examination should be normal in primary ITP aside from bleeding manifestations 1
• Presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes 1
• Constitutional symptoms (fever, weight loss) suggest underlying disorders such as infection or malignancy 1
• Some conditions can present with both thrombocytopenia and thrombosis (antiphospholipid syndrome, heparin-induced thrombocytopenia, thrombotic microangiopathies) 2
• Drug-induced thrombocytopenia should always be considered and may be difficult to exclude 1

By systematically evaluating patients using this framework, clinicians can efficiently determine the cause of thrombocytopenia and initiate appropriate management strategies to prevent serious bleeding complications.