Causes of Thrombocytopenia
Thrombocytopenia is primarily caused by three major mechanisms: decreased platelet production, increased platelet destruction, or splenic sequestration, with various specific conditions falling under each category. 1, 2, 3
Primary Mechanisms of Thrombocytopenia
1. Decreased Platelet Production
- Bone marrow disorders:
- Myelodysplastic syndromes
- Leukemia
- Aplastic anemia
- Vitamin B12 or folate deficiency
- Viral infections affecting bone marrow
- Alcohol toxicity
- Chemotherapy or radiation exposure
2. Increased Platelet Destruction
Immune-mediated destruction:
- Primary immune thrombocytopenia (ITP) - an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets 1
- Secondary immune thrombocytopenia associated with:
- Autoimmune diseases (particularly antiphospholipid antibody syndrome)
- Viral infections (hepatitis C, HIV)
- Medications (drug-induced thrombocytopenia)
Non-immune mediated destruction:
- Disseminated intravascular coagulation (DIC)
- Thrombotic microangiopathies (TTP, HUS)
- HELLP syndrome in pregnancy
3. Splenic Sequestration
- Portal hypertension
- Liver disease with splenomegaly
- Hypersplenism from any cause
4. Other Mechanisms
- Dilutional thrombocytopenia:
- Massive transfusion
- Fluid resuscitation
- Pseudothrombocytopenia:
- Laboratory artifact due to platelet clumping 2
Specific Notable Causes
Heparin-Induced Thrombocytopenia (HIT)
HIT is a serious antibody-mediated reaction occurring in patients treated with heparin. It develops due to antibodies against the heparin-platelet factor 4 complex, inducing platelet aggregation and potentially leading to thrombosis despite low platelet counts. 4, 5
Key features:
- Platelet count typically falls below 100,000/mm³ or decreases by >50% from baseline
- Can occur 2-20 days after starting heparin therapy
- Paradoxically increases risk of venous and arterial thrombosis
- Requires immediate discontinuation of heparin and alternative anticoagulation 4
Immune Thrombocytopenia (ITP)
ITP is an autoimmune disorder where antibodies target platelets for destruction, resulting in isolated thrombocytopenia. 1
Key features:
- Primary ITP occurs in isolation
- Secondary ITP associated with underlying conditions
- Historically attributed solely to increased platelet destruction, but evidence now shows decreased platelet production also contributes 1
- Treatment includes corticosteroids, IVIG, rituximab, or splenectomy in refractory cases 5
Thrombocytopenia in Congenital Heart Disease
In cyanotic congenital heart disease, thrombocytopenia may occur due to:
- Polycythemia and hyperviscosity triggering consumption
- Vascular stasis and widespread platelet deposition
- Platelet counts inversely related to hematocrit levels 1
Clinical Significance Based on Platelet Count
- >50,000/μL: Generally asymptomatic 2, 5
- 20,000-50,000/μL: Mild skin manifestations (petechiae, purpura, ecchymosis) 2
- 10,000-20,000/μL: Increased risk of bleeding
- <10,000/μL: High risk of serious bleeding, may require platelet transfusion 2, 5
Paradoxical Thrombosis with Thrombocytopenia
Some conditions present with both thrombocytopenia and increased thrombosis risk:
- Heparin-induced thrombocytopenia (HIT)
- Antiphospholipid syndrome
- Thrombotic microangiopathies 2
In these cases, anticoagulation rather than platelet transfusion is often required despite low platelet counts 5.
Diagnostic Approach
- Confirm true thrombocytopenia (exclude pseudothrombocytopenia)
- Determine if acute or chronic by reviewing previous platelet counts
- Assess for systemic illness vs. isolated thrombocytopenia
- Evaluate peripheral blood smear for platelet size and morphology
- Consider bone marrow examination when appropriate 1, 2
Remember that while thrombocytopenia is often associated with bleeding risk, certain conditions like HIT paradoxically increase thrombosis risk despite low platelet counts, requiring immediate alternative anticoagulation rather than platelet transfusion.