What is thrombocytopenia?

Thrombocytopenia: Definition, Causes, and Management

Thrombocytopenia is defined as a platelet count less than 150,000 per microliter (150 × 10³/μL) and can result from decreased platelet production, increased destruction, splenic sequestration, or dilution. 1

Clinical Presentation and Severity

The clinical manifestations of thrombocytopenia correlate with platelet count severity:

• >50,000/μL: Generally asymptomatic
• 20,000-50,000/μL: Mild skin manifestations (petechiae, purpura, ecchymosis)
• 10,000-20,000/μL: Increased risk of bleeding
• <10,000/μL: High risk of serious bleeding, including mucosal bleeding and rarely intracranial hemorrhage 1, 2

Causes of Thrombocytopenia

Thrombocytopenia can be classified based on mechanism:

1. Decreased Production

• Bone marrow disorders (leukemia, aplastic anemia)
• Vitamin deficiencies (B12, folate)
• Viral infections (HIV, hepatitis)
• Alcohol consumption
• Chemotherapy

2. Increased Destruction

• Immune thrombocytopenia (ITP): Primary autoimmune disorder
• Drug-induced thrombocytopenia: Common medications include heparin, quinidine/quinine, sulfonamides 2
• Heparin-induced thrombocytopenia (HIT): Immune-mediated prothrombotic disorder characterized by platelet count drop and increased thrombosis risk 2, 3
• Thrombotic microangiopathies (TTP, HUS)

3. Splenic Sequestration

• Portal hypertension
• Liver disease
• Hypersplenism

4. Other Causes

• Pseudothrombocytopenia (laboratory artifact due to EDTA-induced platelet clumping) 2
• Pregnancy-associated
• Dilutional (massive transfusion)

Diagnostic Approach

1. Confirm true thrombocytopenia: Rule out pseudothrombocytopenia by examining peripheral blood smear 2

2. History and physical examination:

   • Medication history (heparin, alcohol, quinidine/quinine, sulfonamides)
   • Transfusion history
   • Family history of thrombocytopenia
   • Bleeding symptoms
   • Comorbid conditions increasing bleeding risk
   • Physical exam for splenomegaly (absence suggests ITP), lymphadenopathy, signs of liver disease 2, 3

3. Laboratory evaluation:

   • Complete blood count with differential
   • Peripheral blood smear examination
   • Coagulation studies
   • Liver function tests
   • Vitamin B12 and folate levels
   • Thyroid function tests
   • HIV and hepatitis screening
   • Autoimmune markers (ANA, antiphospholipid antibodies) 3

4. Additional testing based on clinical suspicion:

   • Bone marrow examination
   • HIT antibody testing
   • Platelet-associated IgG assay (not recommended for routine diagnosis) 2

Special Considerations

Heparin-Induced Thrombocytopenia (HIT)

• Paradoxically increases thrombosis risk despite low platelet counts
• Evaluate using 4T score (Thrombocytopenia, Timing of onset, Thrombosis, other causes of Thrombocytopenia)
• Requires immediate alternative anticoagulation with direct thrombin inhibitors or factor Xa inhibitors 2, 3

Immune Thrombocytopenia (ITP)

• Diagnosis of exclusion
• Characterized by isolated thrombocytopenia without other cytopenias
• Absence of splenomegaly (present in <3% of ITP patients) 2
• Affects quality of life through bleeding risk, activity restrictions, and treatment burden 2

Management Approach

Treatment depends on the underlying cause, severity of thrombocytopenia, and presence of bleeding:

1. Observation: Appropriate for asymptomatic patients with platelet counts >20,000/μL without significant bleeding risk 2

2. Treat underlying cause:

   • Discontinue offending medications
   • Treat infections
   • Manage liver disease

3. Specific treatments for ITP:

   • First-line: Corticosteroids, intravenous immunoglobulin (IVIG) 3, 4
   • Second-line options:
     • Thrombopoietin receptor agonists (romiplostim, eltrombopag) for patients with insufficient response to first-line therapy 5, 6
     • Rituximab
     • Splenectomy
     • Immunosuppressive agents 4

4. Platelet transfusions:

   • Recommended for active hemorrhage
   • Platelet counts <10,000/μL
   • Before invasive procedures (target >50,000/μL) 1

5. Activity restrictions:

   • Patients with platelet counts <50,000/μL should avoid trauma-associated activities 1

Monitoring and Follow-up

• Regular monitoring of platelet counts
• Assessment for bleeding symptoms
• Evaluation of response to therapy
• Monitoring for treatment-related adverse effects

Prognosis

• Varies widely based on underlying cause
• Childhood ITP: High spontaneous remission rates (62-74% at 1 year)
• Adult ITP: 20-45% achieve complete remission by 6 months 2
• Mortality risk is increased 1.3-2.2 fold in adults with ITP compared to general population 2

Thrombocytopenia management requires careful consideration of the underlying cause, bleeding risk, and individual patient factors to optimize outcomes and minimize complications.