Key Facts

HIT is a serious immune-mediated adverse drug reaction that paradoxically causes a hypercoagulable state despite thrombocytopenia. It requires immediate recognition and cessation of heparin.

Epidemiology

• Incidence with UFH: 1-5% (highest risk – orthopaedic/cardiac surgery)
• Incidence with LMWH: <0.1-1%
• More common after surgical than medical heparin use
• Both arterial and venous thrombosis may occur

Aetiology

• Type I (non-immune): mild, transient platelet drop within first 2 days; non-immune, clinically insignificant; no treatment change needed
• Type II (immune-mediated HIT): clinically significant – IgG antibodies against PF4-heparin complexes
• Any heparin product can cause it: UFH > LMWH > fondaparinux (extremely rare)

Pathophysiology

• Heparin binds to platelet factor 4 (PF4) released from platelet alpha-granules
• PF4-heparin complexes become neoantigens → IgG antibody formation
• IgG-PF4-heparin immune complexes bind to platelet FcγRIIa receptors → massive platelet activation
• Activated platelets release procoagulant microparticles → thrombin generation → thrombosis
• Platelet consumption → thrombocytopenia
• Endothelial activation and tissue factor expression contribute to prothrombotic state
• Net result: thrombosis (not bleeding) despite low platelets

Typical Presentation

• Platelet drop ≥50% from baseline (or <150 × 10⁹/L), typically days 5-10 after heparin start
• Nadir platelet count usually 50-80 × 10⁹/L (rarely <20)
• Venous thrombosis more common than arterial (ratio ~4:1)
  • DVT, PE, cerebral venous sinus thrombosis, adrenal vein thrombosis (adrenal haemorrhagic infarction)
• Arterial thrombosis: limb ischaemia, stroke, MI
• Skin necrosis at heparin injection sites

Rapid-Onset HIT

• Platelet drop within 24 hours of heparin re-exposure (prior sensitisation within last 100 days)

Red Flags

• New thrombosis while on heparin → consider HIT
• Skin necrosis at injection sites → pathognomonic
• Acute limb ischaemia → may be first presentation
• Adrenal crisis (bilateral adrenal haemorrhage from adrenal vein thrombosis)

Bedside

• 4T score calculation (most important initial step)
  • Thrombocytopenia, Timing, Thrombosis, oTher causes
  • Score 0-3: low probability; 4-5: intermediate; 6-8: high

Bloods

• Serial FBC: document platelet trend and ≥50% drop
• Anti-PF4/heparin antibodies (ELISA): high sensitivity (~99%) but lower specificity
  • Negative ELISA essentially rules out HIT
• Serotonin release assay (SRA) or heparin-induced platelet activation (HIPA): functional assays, gold standard (high specificity ~98%) – send to reference lab
• Coagulation screen: usually normal (unless concurrent DIC)

Imaging

• Doppler ultrasound: bilateral lower limb DVT screening in confirmed HIT (even without symptoms – 50% have subclinical DVT)
• CTPA: if PE suspected

Special Tests

• Combined clinical (4T score) + immunological (anti-PF4 ELISA) + functional (SRA) approach provides highest diagnostic accuracy

Non-pharmacological

• STOP ALL HEPARIN IMMEDIATELY – includes flushes, heparin-coated catheters, LMWH
• Inform pharmacy and nursing staff to prevent inadvertent re-exposure
• Document allergy in medical records

Pharmacological

Alternative anticoagulation (start immediately, do NOT wait for lab confirmation if 4T score intermediate/high):

• Argatroban (direct thrombin inhibitor): 2mcg/kg/min IV infusion, titrate to APTT 1.5-3× baseline; hepatically cleared (preferred in renal impairment)
• Fondaparinux 5-10mg SC OD (weight-based): commonly used as alternative; renally cleared
• Bivalirudin: used in cardiac surgery/PCI setting
• DOACs (rivaroxaban, apixaban): may be used once platelets recovering and acute thrombosis stable

DO NOT:

• Give warfarin until platelets >150 × 10⁹/L and on alternative anticoagulant (warfarin acutely → protein C depletion → skin necrosis/venous limb gangrene)
• Give platelet transfusions (fuels thrombosis) unless life-threatening haemorrhage

Duration of anticoagulation:

• Without thrombosis: at least 4 weeks of therapeutic anticoagulation
• With thrombosis: at least 3 months
• Transition to warfarin or DOAC once platelets >150

Referral Criteria

• All suspected HIT → haematology urgently
• Limb-threatening thrombosis → vascular surgery

• Thrombosis risk without treatment: 30-50% in first 30 days
• With prompt recognition and treatment, outcomes significantly improved
• Mortality: 5-10% with appropriate management
• Limb loss: 5-10% (amputation due to arterial thrombosis)
• Antibodies typically become undetectable after ~100 days (heparin re-exposure may be considered after this if anti-PF4 negative)
• Future heparin use: may be considered for short periods (e.g., cardiac surgery) once antibodies cleared, with expert guidance

4T Scoring System