What conditions can cause thrombocytopenia?

Causes of Thrombocytopenia

Thrombocytopenia can be caused by a wide range of conditions including autoimmune disorders, infections, bone marrow diseases, medications, liver disease, and genetic disorders, with each requiring specific diagnostic approaches and management strategies. 1, 2

Major Categories of Thrombocytopenia

1. Decreased Platelet Production

• Bone marrow disorders:
  • Leukemia and other malignancies
  • Myelodysplastic syndromes
  • Aplastic anemia
  • Fibrosis
  • Megaloblastic anemia 1
• Nutritional deficiencies:
  • Vitamin B12 deficiency
  • Folate deficiency 2
• Viral infections affecting bone marrow:
  • HIV
  • COVID-19 2

2. Increased Platelet Destruction

• Immune-mediated:
  • Primary immune thrombocytopenia (ITP)
  • Secondary autoimmune thrombocytopenia associated with:
    • HIV, HCV infections
    • Systemic lupus erythematosus (SLE)
    • Other autoimmune disorders
    • Lymphoproliferative disorders 1
  • Drug-induced immune thrombocytopenia
  • Heparin-induced thrombocytopenia (HIT) 2
• Non-immune mediated:
  • Thrombotic thrombocytopenic purpura (TTP)
  • Hemolytic uremic syndrome (HUS)
  • Disseminated intravascular coagulation (DIC)
  • HELLP syndrome in pregnancy 3

3. Drug-Induced Thrombocytopenia

• Heparin (unfractionated > LMWH)
• Quinidine
• Sulfonamides
• Sulfonylureas
• Quinine (even in tonic water)
• Alcohol 1, 2

4. Splenic Sequestration

• Portal hypertension
• Liver cirrhosis
• Hypersplenism 3

5. Dilutional Thrombocytopenia

• Massive transfusion
• Fluid resuscitation 3

6. Genetic/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

Diagnostic Approach

Initial Assessment

1. Confirm true thrombocytopenia:

   • Rule out pseudothrombocytopenia (EDTA-dependent platelet agglutination) by collecting blood in heparin or sodium citrate tubes 1, 3
   • Examine peripheral blood smear

2. Determine timing:

   • Acute vs. chronic thrombocytopenia
   • Review previous platelet counts if available 3

3. Assess for systemic illness:

   • Fever, weight loss, lymphadenopathy, hepatomegaly
   • Constitutional symptoms suggest underlying disorder (HIV, SLE, lymphoproliferative disease) 1

Key Diagnostic Considerations

• Isolated thrombocytopenia without other abnormalities most likely indicates:

  • Immune thrombocytopenia (ITP)
  • Drug-induced thrombocytopenia 3

• Thrombocytopenia with abnormal blood counts suggests:

  • Bone marrow disorders
  • Nutritional deficiencies
  • Systemic diseases 1

• Thrombocytopenia with thrombosis requires urgent evaluation for:

  • Heparin-induced thrombocytopenia (HIT) - use 4T score for assessment
  • Antiphospholipid syndrome
  • Thrombotic microangiopathies 2, 3

Special Considerations

Heparin-Induced Thrombocytopenia (HIT)

• Occurs 5-14 days after heparin exposure
• Paradoxically associated with thrombosis rather than bleeding
• Higher risk in surgical patients (especially cardiac and orthopedic)
• Women have approximately twice the risk compared to men
• Requires immediate discontinuation of heparin and alternative anticoagulation 2

Emergency Causes Requiring Hospitalization

• Heparin-induced thrombocytopenia
• Thrombotic microangiopathies
• HELLP syndrome
• Severe ITP with bleeding 3

Management Principles

• Platelet transfusion indicated for:

  • Active hemorrhage
  • Platelet count <10,000/μL
  • Before invasive procedures with high bleeding risk 3

• Important caveat: Avoid platelet transfusion in conditions where thrombocytopenia is associated with thrombosis (HIT, TTP) as this may worsen thrombosis 2

• Activity restrictions recommended for patients with platelet counts <50,000/μL to avoid trauma-associated bleeding 3

By systematically evaluating patients with thrombocytopenia and considering these various etiologies, clinicians can determine the underlying cause and implement appropriate management strategies to improve outcomes.