What are the common causes of thrombocytopenia?

Common Causes of Thrombocytopenia

The most common causes of thrombocytopenia include bone marrow disorders, immune-mediated destruction, infections, medications, and splenic sequestration, with the diagnostic approach requiring careful evaluation of peripheral blood smear and consideration of bone marrow examination in selected cases. 1

Major Categories of Thrombocytopenia

Decreased Platelet Production

• Bone marrow disorders, including myelodysplastic syndromes, leukemias, and other malignancies, can impair megakaryocyte function and platelet production 1
• Inherited thrombocytopenias, such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, and MYH9-related disease affect platelet production 1
• Viral infections, particularly HIV and hepatitis C, can suppress bone marrow production of platelets 1, 2
• Chronic bone marrow failure states including aplastic anemia and graft failure can cause prolonged thrombocytopenia 3

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 diseases (e.g., systemic lupus erythematosus) 2
  • Lymphoproliferative disorders (e.g., chronic lymphocytic leukemia) 1, 2
  • Infections (H. pylori, HIV, hepatitis C) 1, 2
• Heparin-induced thrombocytopenia (HIT) - a serious antibody-mediated reaction that can progress to thrombosis 4, 5
• Thrombotic microangiopathies (TTP, HUS) which can present as emergencies requiring hospitalization 5

Other Mechanisms

• Splenic sequestration, commonly seen in liver disease with portal hypertension 5, 6
• Dilutional thrombocytopenia from massive transfusions 5
• Drug-induced thrombocytopenia from numerous medications 5, 6
• Alcohol-related thrombocytopenia, which is generally benign despite low platelet counts 7
• Pregnancy-related conditions including HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) 5

Diagnostic Approach

Initial Evaluation

• Confirm true thrombocytopenia by collecting blood in a tube containing heparin or sodium citrate to exclude pseudothrombocytopenia 1, 5
• Complete blood count with differential to identify isolated thrombocytopenia versus pancytopenia 1
• Peripheral blood smear examination is essential to rule out pseudothrombocytopenia and evaluate for other causes 1, 7
• Review of medication history, particularly for drugs associated with thrombocytopenia (e.g., heparin) 4, 5

Further Testing

• Testing for HIV and hepatitis C should be considered in adults with typical immune thrombocytopenia 1
• Bone marrow examination may be necessary in selected cases, such as patients older than 60 years or those with systemic symptoms 1, 7
• For alcohol-related thrombocytopenia, assess for liver disease including alcoholic liver cirrhosis 7

Clinical Presentation and Management Considerations

Clinical Manifestations

• Patients with platelet counts >50,000/μL are generally asymptomatic 5
• Platelet counts between 20,000-50,000/μL may present with mild skin manifestations (petechiae, purpura, ecchymosis) 5
• Platelet counts <10,000/μL carry a high risk of serious bleeding 5
• Some conditions (antiphospholipid syndrome, HIT, thrombotic microangiopathies) can paradoxically present with both bleeding and thrombosis 5

Management Pearls

• Platelet transfusion is recommended for active hemorrhage or platelet counts <10,000/μL 5
• For primary immune thrombocytopenia in children with no bleeding or mild bleeding, observation alone is recommended regardless of platelet count 1
• For pediatric patients requiring treatment, a single dose of IVIg or a short course of corticosteroids is recommended as first-line treatment 1
• In HIT, promptly discontinue heparin if platelet count falls below 100,000/mm³ or if recurrent thrombosis develops 4
• Activity restrictions are advised for patients with platelet counts <50,000/μL to avoid trauma-associated bleeding 5

Special Considerations

Alcohol-Related Thrombocytopenia

• Obtain comprehensive alcohol use history, including duration and quantity of consumption 7
• Avoid medications that affect platelet function (NSAIDs, antiplatelet agents) in patients with alcohol-related thrombocytopenia 7
• Be aware that thrombocytopenia in alcoholics is generally benign, with clinically significant hemorrhage being rare despite low counts 7

Heparin-Induced Thrombocytopenia

• HIT can occur 2-20 days (average 5-9 days) following the onset of heparin therapy 4
• Monitor platelet counts before and periodically during heparin therapy 4
• HIT may progress to venous and arterial thromboses (HITT), which can present as deep vein thrombosis, pulmonary embolism, stroke, or myocardial infarction 4
• HIT or HITT can occur up to several weeks after discontinuation of heparin therapy 4