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

Heparin-Induced Thrombocytopenia Classes

There are two distinct classes of heparin-induced thrombocytopenia (HIT): 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 mediated thrombocytopenia
  • Early onset (typically within first 2 days of heparin exposure)
  • Mild decrease in platelet count (rarely below 100,000/mm³)
  • Self-limiting even with continued heparin therapy
  • No thrombotic complications
  • No specific treatment required

• Pathophysiology:

  • Direct pro-aggregating effect of heparin on platelets
  • Not antibody-mediated
  • No clinical significance

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
  • Potentially life-threatening condition requiring immediate intervention

• Pathophysiology:

  • Mediated by IgG antibodies against platelet factor 4 (PF4)-heparin complexes
  • Antibodies bind to PF4/heparin complexes on platelet surfaces
  • Fc portion of antibodies activates platelets via FcγRIIa receptors
  • Results in massive platelet activation and thrombin generation
  • Activated platelets release procoagulant microparticles
  • Multi-cellular activation involving platelets, endothelial cells, neutrophils, and monocytes
  • Elimination of sensitized platelets by the mononuclear phagocyte system

Risk Levels for Developing HIT

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

Risk Level	Incidence	Clinical Scenarios
Low (<0.1%)	<1 in 1000	- LMWH in medical patients (non-cancer) - LMWH in obstetrics (non-surgical) - Fondaparinux therapy - Single UFH injection for procedures - Any heparin therapy >1 month
Intermediate (0.1-1%)	1-10 in 1000	- Prophylactic UFH in medical/obstetric patients - LMWH in cancer patients - LMWH in severe trauma - LMWH post-operatively (including cardiac surgery)
High (>1%)	>10 in 1000	- Prophylactic UFH in surgical patients - UFH for circulatory assistance - UFH for renal replacement therapy - All curative UFH treatments

Special HIT Variants

Recent literature has identified several HIT-like syndromes that share pathophysiological features with classical HIT 1:

• Autoimmune HIT (aHIT): Serological evidence of platelet activation in absence of therapeutic heparin doses

  • Spontaneous aHIT: No antecedent heparin exposure
  • Persistent aHIT: Ongoing thrombocytopenia >1 week after heparin discontinuation

• Delayed-onset HIT: Thrombocytopenia/thrombosis occurring after heparin has been discontinued

• Fondaparinux-associated HIT: Rare cases of HIT triggered by fondaparinux

Clinical Implications and Management

When HIT is suspected or confirmed 1, 2:

1. Immediately discontinue all forms of heparin (including heparin flushes and heparin-coated catheters)
2. Initiate alternative non-heparin anticoagulation despite thrombocytopenia
3. Avoid platelet transfusions unless life-threatening bleeding
4. Avoid warfarin initiation until platelet count recovers to >150,000/mm³

Diagnostic Approach

Diagnosis requires both clinical assessment and laboratory confirmation 1:

1. Clinical probability assessment using 4T score:

   • Thrombocytopenia (degree of platelet count fall)
   • Timing of platelet count fall
   • Thrombosis or other sequelae
   • Other causes of thrombocytopenia

2. Laboratory testing:

   • Immunoassays to detect anti-PF4/heparin antibodies (high sensitivity)
   • Functional assays to detect platelet-activating antibodies (high specificity)

Common Pitfalls

• Failing to recognize HIT in patients with thrombocytopenia receiving heparin
• Overdiagnosing HIT based solely on positive immunoassays without clinical correlation
• Delaying alternative anticoagulation while awaiting laboratory confirmation
• Initiating warfarin before platelet recovery, which can precipitate venous limb gangrene
• Failing to recognize HIT variants such as delayed-onset or autoimmune HIT

By understanding the different classes of HIT and their clinical implications, clinicians can promptly identify and appropriately manage this potentially life-threatening condition.