What are the causes of thrombocytopenia?

Causes of Thrombocytopenia

Thrombocytopenia can be caused by decreased platelet production, increased peripheral destruction, splenic sequestration, or dilution, with the most common causes being immune-mediated destruction, drug-induced effects, and infections. 1, 2

Primary Classification of Causes

Thrombocytopenia (platelet count <150 × 10³/μL) can be categorized into several major mechanisms:

1. Decreased Platelet Production

• Bone marrow disorders:

  • Myelodysplastic syndromes
  • Leukemias and other malignancies
  • Bone marrow fibrosis
  • Aplastic anemia
  • Megaloblastic anemia 1

• Inherited thrombocytopenias:

  • Thrombocytopenia-absent radius (TAR) syndrome
  • Wiskott-Aldrich syndrome
  • MYH9-related disease
  • Bernard-Soulier syndrome
  • Type IIB von Willebrand disease 1

2. Increased Peripheral Destruction

• Immune-mediated:

  • Primary immune thrombocytopenia (ITP)
  • Secondary immune thrombocytopenia associated with:
    • Autoimmune disorders (SLE, antiphospholipid syndrome)
    • Infections (HIV, HCV)
    • Lymphoproliferative disorders 1

• Non-immune mediated:

  • Disseminated intravascular coagulation (DIC)
  • Thrombotic thrombocytopenic purpura (TTP)
  • Hemolytic uremic syndrome (HUS)
  • HELLP syndrome in pregnancy 2
  • Heparin-induced thrombocytopenia (HIT) 1

3. Splenic Sequestration

• Liver disease/cirrhosis
• Portal hypertension
• Hypersplenism 1, 3

4. Dilutional Thrombocytopenia

• Massive transfusion
• Fluid resuscitation 3

5. Pseudothrombocytopenia

• EDTA-dependent platelet agglutination 1

Specific Clinical Scenarios

Intensive Care Unit Setting

In critically ill patients, the most common causes are:

• Sepsis
• Trauma
• Drug-induced thrombocytopenia
• Heparin-induced thrombocytopenia
• DIC 3

Drug-Induced Thrombocytopenia

Common medications associated with thrombocytopenia include:

• Heparin (HIT)
• Antibiotics (sulfonamides, vancomycin)
• Anticonvulsants
• Quinine/quinidine
• GPIIb-IIIa inhibitors (used in acute coronary syndromes) 1

Post-Surgical Setting

• Perioperative hemodilution
• Platelet consumption in extracorporeal circuits
• Consumption thrombocytopenia after cardiac surgery
• Ventricular assistance devices
• Extracorporeal membrane oxygenation 1

Diagnostic Approach

When evaluating thrombocytopenia, consider:

1. Rule out pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the count 2

2. Examine peripheral blood smear to identify:

   • Schistocytes (suggesting TTP/HUS)
   • Leukocyte inclusion bodies (MYH9-related disease)
   • Abnormal platelet size or morphology (inherited thrombocytopenias) 1

3. Consider timing:

   • Acute vs. chronic thrombocytopenia
   • Timing in relation to medication exposure (e.g., 5-10 days after heparin initiation for HIT) 1

4. Evaluate for associated conditions:

   • Infections (HIV, HCV)
   • Autoimmune disorders
   • Recent transfusions (post-transfusion purpura)
   • Recent vaccinations
   • Liver disease 1

Clinical Pearls and Pitfalls

• Not all thrombocytopenia causes bleeding: Conditions like HIT and antiphospholipid syndrome can paradoxically cause thrombosis despite low platelet counts 2

• Severity correlation: Platelet counts >50 × 10³/μL are generally asymptomatic, 20-50 × 10³/μL may have mild skin manifestations, and <10 × 10³/μL carry high risk of serious bleeding 2

• Bone marrow examination: Consider in patients >60 years, those with systemic symptoms or abnormal signs, or when splenectomy is being considered 1

• Platelet transfusion caution: While beneficial in production defects, transfusions may be harmful in conditions with increased intravascular platelet activation like TTP or HIT 3

Understanding the mechanism of thrombocytopenia is crucial for appropriate management, as treatment strategies differ significantly depending on the underlying cause.