What causes a drop in platelet count (thrombocytopenia)?

Causes of Thrombocytopenia (Low Platelet Count)

Thrombocytopenia can result from decreased platelet production, increased destruction, splenic sequestration, or dilution, with specific causes requiring different management approaches. 1, 2

Primary Mechanisms of Thrombocytopenia

1. Decreased Platelet Production

• Bone marrow disorders:
  • Leukemia
  • Myelodysplastic syndromes
  • Aplastic anemia
  • Bone marrow infiltration by malignancy
• Nutritional deficiencies:
  • Vitamin B12 deficiency
  • Folate deficiency
• Viral infections affecting bone marrow function

2. Increased Platelet Destruction

• Immune-mediated destruction:
  • Idiopathic Thrombocytopenic Purpura (ITP): Autoimmune disorder causing antibody-mediated platelet destruction 1
  • Drug-induced thrombocytopenia: Common culprits include:
    • Heparin (causing HIT)
    • Quinidine
    • Sulfonamides
    • Sulfonylureas
    • Dipyridamole
    • Salicylates 1
  • Heparin-Induced Thrombocytopenia (HIT): Antibody formation against platelet factor 4-heparin complex 1, 3, 4
• Non-immune destruction:
  • Disseminated Intravascular Coagulation (DIC)
  • Thrombotic Thrombocytopenic Purpura (TTP)
  • Hemolytic Uremic Syndrome (HUS)

3. Splenic Sequestration

• Hypersplenism due to:
  • Liver disease with portal hypertension
  • Myelofibrosis
  • Lymphoma
  • Gaucher disease

4. Dilutional Thrombocytopenia

• Massive blood transfusion
• Fluid resuscitation

5. Pseudothrombocytopenia

• EDTA-induced platelet clumping (occurs in about 0.1% of adults) 1

Specific Clinical Conditions Associated with Thrombocytopenia

Immune-Mediated Conditions

1. Idiopathic Thrombocytopenic Purpura (ITP)

   • Primary autoimmune disorder
   • Characterized by isolated thrombocytopenia without other causes 1

2. Heparin-Induced Thrombocytopenia (HIT)

   • Antibody-mediated reaction to heparin-PF4 complex
   • Typically occurs 5-14 days after heparin initiation
   • Can occur earlier if patient exposed to heparin in previous 3 months
   • Moderate thrombocytopenia (30-70 G/L)
   • Paradoxically associated with thrombosis rather than bleeding 1, 3, 5

3. Drug-Induced Thrombocytopenia

   • Common medications include:
     • Heparin
     • Quinidine/quinine
     • Sulfonamides
     • Alcohol
     • GPIIb-IIIa inhibitors 1

Infection-Related Thrombocytopenia

• Bacterial infections (especially sepsis)
• Viral infections:
  • HIV
  • Dengue fever
  • Viral hepatitis
  • COVID-19 1, 6

Pregnancy-Related Thrombocytopenia

• Gestational thrombocytopenia
• Preeclampsia
• HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) 2, 7

Thrombotic Microangiopathies

• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome (HUS)
• Characterized by microangiopathic hemolytic anemia and thrombocytopenia 2, 7

Clinical Presentation and Severity

• Mild thrombocytopenia (>50,000/μL): Usually asymptomatic
• Moderate thrombocytopenia (20,000-50,000/μL): May present with petechiae, purpura, or ecchymosis
• Severe thrombocytopenia (<10,000/μL): High risk of serious bleeding 2

Key Diagnostic Considerations

1. Confirm true thrombocytopenia by examining peripheral blood smear to exclude pseudothrombocytopenia
2. Determine timing (acute vs. chronic)
3. Assess for systemic illness - isolated thrombocytopenia suggests ITP or drug-induced causes
4. Review medication history - particularly heparin, quinidine, sulfonamides, and alcohol
5. Evaluate for bleeding or thrombosis - paradoxical thrombosis suggests HIT or antiphospholipid syndrome 1, 2

Critical Warning Signs

• Platelet count <10,000/μL
• Active bleeding
• Concurrent thrombosis with thrombocytopenia (suggests HIT, TTP, or antiphospholipid syndrome)
• Rapid decline in platelet count
• Associated systemic symptoms (fever, neurological changes, renal dysfunction) 1, 2

Remember that while thrombocytopenia typically increases bleeding risk, certain conditions like HIT paradoxically increase thrombosis risk, requiring immediate anticoagulation rather than platelet transfusion 1, 3, 5.