What are the types of heparin-induced thrombocytopenia (HIT)?

Types of Heparin-Induced Thrombocytopenia (HIT)

There are two distinct types of heparin-induced thrombocytopenia: Type I (non-immune) and Type II (immune-mediated), with only Type II being clinically significant and properly referred to as HIT. 1

Type I HIT

• Characteristics:

  • Benign, non-immune origin
  • Early onset (usually within first 2 days of heparin therapy)
  • Mild thrombocytopenia (rarely below 100,000/mm³)
  • No thrombotic complications
  • Platelet count typically regresses despite continued heparin therapy 2

• Mechanism:

  • Direct effect of heparin on platelets causing mild aggregation
  • Not antibody-mediated
  • No clinical significance and does not require discontinuation of heparin 3

Type II HIT (True HIT)

• Characteristics:

  • Immune-mediated syndrome
  • Delayed onset (typically 5-10 days after heparin initiation)
  • Moderate to severe thrombocytopenia (often >50% drop in platelet count)
  • Paradoxically associated with thrombosis rather than bleeding 2, 4

• Mechanism:

  • Caused by IgG antibodies that recognize heparin-modified platelet factor 4 (PF4/H)
  • Leads to intense platelet activation and explosive thrombin generation
  • Results in massive platelet activation and elimination by the mononuclear phagocyte system 2

• Clinical significance:

  • Potentially life-threatening condition
  • High risk of venous and/or arterial thrombosis
  • Requires immediate discontinuation of all heparin products and alternative anticoagulation 4

Emerging HIT-like Syndromes

Recent literature has identified several HIT-like syndromes that share pathophysiological features with classical HIT 2:

1. Autoimmune HIT (aHIT):

   • Serological evidence of platelet activation in the absence of therapeutic heparin
   • Antibodies can bridge PF4 tetramers without requiring polysulfated chains like heparin
   • Subtypes include:
     • Spontaneous aHIT: No antecedent heparin exposure
     • Persistent aHIT: Ongoing thrombocytopenia for longer than 1 week after heparin discontinuation 2

2. Delayed-onset HIT:

   • Thrombocytopenia and thrombosis occurring after heparin has been discontinued
   • Can develop up to several weeks after stopping heparin therapy 4

3. Fondaparinux-associated HIT:

   • Rare cases of HIT-like syndrome associated with fondaparinux use
   • Mechanistically similar to classical HIT 2, 5

4. Flush heparin HIT:

   • Associated with small amounts of heparin used to maintain catheter patency
   • Can occur even with minimal heparin exposure 2

5. HIT-associated disseminated intravascular coagulation:

   • Severe form with widespread microvascular thrombosis 2

Risk Factors for Developing HIT

The risk of developing HIT varies based on patient factors and type of heparin used 1:

• Low risk (<0.1%):

  • LMWH in medical patients (non-cancer)
  • LMWH in obstetrics (non-surgical)
  • Fondaparinux therapy
  • Single UFH injection for procedures
  • Any heparin therapy >1 month

• Intermediate risk (0.1-1%):

  • Prophylactic UFH in medical/obstetric patients
  • LMWH in cancer patients
  • LMWH in severe trauma
  • LMWH post-operatively (including cardiac surgery)

• High risk (>1%):

  • Prophylactic UFH in surgical patients
  • UFH for circulatory assistance
  • UFH for renal replacement therapy
  • All curative UFH treatments 1

Clinical Implications

Understanding the different types of HIT is crucial for proper management:

• For Type I HIT: Monitoring without discontinuation of heparin is usually sufficient
• For Type II HIT: Immediate discontinuation of all heparin products, initiation of alternative non-heparin anticoagulation, and avoidance of platelet transfusions unless life-threatening bleeding occurs 4

While rare, HIT Type II is a potentially fatal syndrome that can develop even years after the start of heparin therapy, as documented in a case report of a patient who developed HIT after 24 years on hemodialysis 6.