Types of Heparin-Induced Thrombocytopenia
There are two distinct types of heparin-induced thrombocytopenia: Type I (benign, non-immune, early-onset) and Type II (immune-mediated, potentially life-threatening), with Type II being the clinically significant form that requires immediate intervention. 1
Type I HIT (Non-Immune)
Type I HIT is a benign thrombocytopenia with the following characteristics: 1
- Non-immune origin - does not involve antibody formation 1
- Early onset - typically occurs within the first 2 days of heparin exposure 1
- Mild thrombocytopenia - platelet count rarely drops below 100 × 10⁹/L 2
- Self-limiting - resolves spontaneously despite continued heparin therapy 1
- No thrombotic complications - clinically insignificant 1, 2
- No treatment required - heparin can be safely continued 2
Type II HIT (Immune-Mediated)
Type II HIT is the clinically significant, potentially catastrophic form that warrants the designation "HIT" in clinical practice: 1
Core Pathophysiology
- IgG antibody-mediated against platelet factor 4 (PF4)/heparin complexes 1, 3
- Delayed onset - typically 5-8 days after heparin initiation 1, 2
- Moderate thrombocytopenia - platelet count usually <100 × 10⁹/L or >50% drop from baseline 1, 2
- Paradoxical prothrombotic state - high risk of venous and/or arterial thrombosis despite low platelets 1, 3
- Multi-cellular activation - involves platelets, endothelial cells, neutrophils, and monocytes expressing tissue factor 1
Clinical Subtypes of Type II HIT
Recent expert consensus has identified three important HIT-like subtypes that require distinct recognition: 1
Spontaneous Autoimmune HIT
- No antecedent heparin exposure 1
- Clinical features identical to classic HIT 1
- Positive HIT serology with functional assay positive in buffer (without heparin) 1
- Anti-PF4 antibodies can bridge PF4 tetramers without requiring heparin 1
- Strong expert support (85.6%) for IVIg treatment 1
Persistent Autoimmune HIT
- Antecedent heparin exposure present 1
- Failure to recover platelets within 1 week after heparin discontinuation 1
- Positive HIT serology with functional assay positive in buffer 1
- Strong expert support (83.7%) for IVIg treatment 1
Treatment-Refractory HIT
- Progression of thrombocytopenia and/or thrombosis despite heparin discontinuation and appropriate non-heparin anticoagulation 1
- Positive routine HIT functional testing 1
- Includes fondaparinux-associated HIT 1
- Strong expert support (87.4%) for IVIg treatment 1
Other Rare Variants
Additional uncommon presentations include: 1
- Delayed-onset HIT - thrombocytopenia occurring after heparin cessation 1
- Fondaparinux-associated HIT - despite fondaparinux being considered low-risk 1
- Flush heparin HIT - from minimal heparin exposure 1
- HIT-associated disseminated intravascular coagulation 1
Critical Clinical Distinction
The key distinction is that only Type II HIT requires immediate heparin cessation and alternative anticoagulation - Type I can be safely observed with continued heparin. 1, 4, 2 The 4Ts score should be calculated to determine probability: if ≤3 (low probability), HIT is excluded; if 4-5 (intermediate) or ≥6 (high), immediately stop all heparin and initiate alternative anticoagulation before laboratory confirmation. 4
Common Pitfall
Never delay stopping heparin and starting alternative anticoagulation while awaiting laboratory confirmation in patients with intermediate or high clinical probability - biological assays often take several days but must never delay treatment initiation. 1, 4 The mortality and thrombosis risk is substantial: argatroban reduces deaths by 134 per 1,000 patients (RR 0.12) and thrombotic events by 191 per 1,000 (RR 0.45) compared to heparin discontinuation alone in HIT with thrombosis. 4