What causes a drop in platelet count (thrombocytopenia)?

Causes of Thrombocytopenia

Thrombocytopenia (platelet count <150 × 10³/μL) can result from decreased platelet production, increased destruction, splenic sequestration, or dilution/clumping, with the most common causes being immune-mediated disorders, medications, infections, bone marrow disorders, and consumptive processes. 1

Major Categories of Thrombocytopenia

1. Decreased Platelet Production

• Bone marrow disorders:
  • Leukemia
  • Myelodysplastic syndromes
  • Aplastic anemia
  • Bone marrow fibrosis
  • Megaloblastic anemia 2

2. Increased Platelet Destruction

• Immune-mediated:

  • Primary immune thrombocytopenia (ITP)
  • Secondary autoimmune thrombocytopenia (associated with HIV, HCV, SLE) 2
  • Heparin-induced thrombocytopenia (HIT) 3, 2
  • Drug-induced immune thrombocytopenia
  • Post-transfusion purpura

• Non-immune mediated:

  • Disseminated intravascular coagulation (DIC)
  • Thrombotic microangiopathies (TTP, HUS)
  • HELLP syndrome in pregnancy 1

3. Splenic Sequestration

• Portal hypertension
• Liver disease with impaired hemostasis 4
• Hypersplenism

4. Other Causes

• Dilutional:
  • Massive transfusion
  • Post-surgical hemodilution 2
• Pseudothrombocytopenia:
  • EDTA-dependent platelet agglutination 2, 1

Medication-Induced Thrombocytopenia

Medications are common reversible causes of thrombocytopenia:

• Heparin: Causes HIT in 1-5% of cardiac/orthopedic surgery patients and 0.1-1% of medical/obstetric patients 3
• Other common culprits:
  • Quinidine
  • Sulfonamides
  • Sulfonylureas
  • Quinine
  • Alcohol 2

Heparin-Induced Thrombocytopenia (HIT)

HIT deserves special attention as it paradoxically increases thrombosis risk despite low platelet counts:

• Mechanism: Formation of antibodies to platelet factor 4-heparin complexes 3
• Timing patterns:
  • Typical onset: 5-10 days after heparin initiation
  • Rapid onset: Within 24 hours in patients with recent heparin exposure
  • Delayed onset: Up to 3 weeks after heparin cessation 3
• Clinical features:
  • Moderate thrombocytopenia (typically 30-70 × 10⁹/L)
  • Venous and arterial thromboses in up to 50% of cases 2, 5

Clinical Approach to Thrombocytopenia

1. Confirm true thrombocytopenia:

   • Rule out pseudothrombocytopenia by collecting blood in heparin or sodium citrate tube 1
   • Examine peripheral blood smear

2. Determine timing:

   • Acute vs. chronic thrombocytopenia (review previous counts) 1
   • For acute cases, determine if emergency hospitalization is needed

3. Assess severity:

   • Mild (>50 × 10³/μL): Generally asymptomatic
   • Moderate (20-50 × 10³/μL): May have petechiae, purpura, ecchymosis
   • Severe (<10 × 10³/μL): High risk of serious bleeding 1

4. Look for associated conditions:

   • Systemic illness
   • Medication exposure
   • Recent heparin exposure
   • Pregnancy
   • Liver disease

Important Clinical Pitfalls

• Thrombocytopenia with thrombosis: When seeing this paradoxical combination, consider HIT, antiphospholipid syndrome, or thrombotic microangiopathies 1

• Delayed HIT: Can occur up to 3 weeks after heparin discontinuation 6

• Cardiac surgery patients: Special pattern where platelet count falls immediately post-CPB, then rises. HIT should be suspected if platelet count falls ≥4 days postoperatively or thrombocytopenia persists ≥4 days after surgery 3

• Women have twice the risk of developing HIT compared to men 3

• Avoid platelet transfusions in HIT: May worsen thrombosis 5

By systematically evaluating the potential causes of thrombocytopenia and recognizing high-risk patterns, clinicians can quickly identify the underlying etiology and implement appropriate management strategies.