What is the management of heparin-induced thrombocytopenia (HIT)?

Management of Heparin-Induced Thrombocytopenia (HIT)

Immediately discontinue all forms of heparin (including flushes and heparin-coated catheters) and start therapeutic-dose non-heparin anticoagulation without waiting for laboratory confirmation when HIT is suspected with intermediate or high clinical probability. 1, 2

Initial Risk Stratification Using 4T Score

Calculate the 4T score to determine pre-test probability and guide immediate management 1, 2:

• Low probability (4T ≤3): HIT can be excluded—continue heparin with close platelet monitoring and pursue alternative causes of thrombocytopenia 1, 2

• Intermediate probability (4T = 4-5): Stop all heparin immediately, initiate therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing 1, 2

• High probability (4T ≥6): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing—do not wait for results before treating 1, 2

Critical caveat: In post-cardiac surgery patients, the 4T score is less reliable; look for a "biphasic" pattern in platelet count evolution which strongly suggests HIT 1

Alternative Anticoagulant Selection

Therapeutic doses are mandatory even without thrombosis due to the high thrombotic risk in HIT—prophylactic doses are insufficient. 1, 2

First-Line Options Based on Organ Function:

• Normal renal and hepatic function: Argatroban at 2 mcg/kg/min as continuous IV infusion, monitoring aPTT to maintain 1.5-3 times baseline 1, 3

• Severe renal impairment (CrCl <30 mL/min): Argatroban is the only recommended agent as it is hepatically metabolized 1, 2, 3

• Severe hepatic impairment (Child-Pugh C): Use bivalirudin, danaparoid, or fondaparinux instead of argatroban 1, 2

• Severe HIT (massive PE, extensive/arterial thrombosis, venous gangrene): Prefer argatroban or bivalirudin with strict biological monitoring due to their short half-lives and reversibility 1, 2

Alternative Agents:

• Bivalirudin: Shorter half-life (20-30 minutes), useful for procedures requiring short-acting anticoagulation, but contraindicated in severe renal failure 1, 2

• Fondaparinux: Acceptable for stable patients without severe renal or hepatic impairment, does not require specific monitoring 2, 4

• Danaparoid: Requires monitoring of anti-Xa activity with specific calibration; not recommended in severe renal failure 1, 2

• Direct oral anticoagulants (DOACs): Acceptable alternatives for long-term anticoagulation 1

Laboratory Testing Strategy

• Intermediate or high probability: Perform anti-PF4 antibody testing (ELISA or chemiluminescent tests) while simultaneously initiating alternative anticoagulation 1, 2

• If anti-PF4 antibodies are positive with intermediate probability: Perform a functional test (serotonin release assay or HIPA test) to confirm diagnosis 1

• If anti-PF4 antibodies are negative with intermediate probability: HIT is excluded and heparin can be resumed with close platelet monitoring 1

Never delay discontinuation of heparin and initiation of alternative anticoagulation while waiting for laboratory results. 1

Transition to Oral Anticoagulation

• Wait for platelet count recovery (>150,000/μL or return to baseline) before transitioning to vitamin K antagonists (VKAs) 1, 2

• Avoid VKAs in the acute phase of HIT as they can potentially cause venous limb gangrene 1, 2

• Overlap parenteral anticoagulant with oral agent for at least 5 days 1, 2

• DOACs are acceptable alternatives to warfarin for long-term anticoagulation 1

Perioperative Management

• For acute HIT (<1 month): Postpone elective surgery beyond the first month if possible 1, 2

• If surgery cannot be delayed: Use short-acting agents like argatroban or bivalirudin—stop argatroban 4 hours before the procedure and bivalirudin 2 hours before 2

• For cardiac surgery with history of HIT: Systematically perform ELISA for anti-PF4 antibodies before surgery; if positive, use direct thrombin inhibitor (bivalirudin or argatroban) instead of heparin 1

Percutaneous Coronary Intervention (PCI) Dosing

For patients with or at risk for HIT undergoing PCI 3:

• Start argatroban at 25 mcg/kg/min with a bolus of 350 mcg/kg administered via large bore IV line over 3-5 minutes 3

• Check activated clotting time (ACT) 5-10 minutes after bolus completion 3

• Proceed if ACT is greater than 300 seconds 3

Critical Pitfalls to Avoid

• Do not give platelet transfusions—they may worsen thrombosis in HIT patients 1, 2

• Do not use prophylactic doses of alternative anticoagulants—therapeutic doses are required even without thrombosis 1, 2

• Do not prescribe oral antiplatelet agents alone to treat acute HIT—they do not effectively prevent thrombosis 2

• Do not insert an inferior vena cava filter in the acute phase of HIT due to increased thrombotic risk 2

• Do not use IV immunoglobulins as first-line treatment for acute HIT 2

Long-term Management

• Document HIT diagnosis in medical records and provide patients with documentation of their diagnosis and laboratory results 1, 2

• Avoid re-exposure to heparin, especially within 3 months of HIT diagnosis 1, 2

• For future anticoagulation needs, use oral anticoagulants (VKA or DOAC) or fondaparinux 1, 2

• Schedule follow-up with hematology within 3 months of diagnosis 1

• Consider extended anticoagulation (3-6 months) depending on the clinical situation 2