Management of Heparin-Induced Thrombocytopenia (HIT)
Immediately discontinue all heparin and start argatroban at 2 mcg/kg/min as a continuous IV infusion—do not give platelet transfusions as they worsen thrombosis in HIT patients. 1, 2
Immediate Actions Required
Stop all heparin exposure immediately including heparin flushes and heparin-coated catheters, even before laboratory confirmation if clinical suspicion is intermediate or high. 3, 1 This is the critical first step that must not be delayed.
Initiate therapeutic-dose argatroban without waiting for antibody test results. 1, 2 The standard starting dose is 2 mcg/kg/min as continuous IV infusion for patients with normal hepatic function. 4 Reduce the initial dose to 0.5 mcg/kg/min if the patient has moderate or severe hepatic impairment, heart failure, multiple organ dysfunction, or is post-cardiac surgery. 3, 5
Why Argatroban Over Other Options
Argatroban is preferred as first-line therapy because it is a direct thrombin inhibitor with a short half-life (approximately 45 minutes), allowing for rapid titration and reversal. 5 It has been extensively studied in prospective trials showing significant reduction in new thrombosis (RR 0.29) and death due to thrombosis compared to discontinuing heparin alone. 3
Argatroban is the only alternative anticoagulant suitable for patients with severe renal impairment since it undergoes hepatic metabolism rather than renal clearance. 1, 6 This is a critical advantage over bivalirudin, which is contraindicated when creatinine clearance is below 30 mL/min. 1
Why NOT Platelet Transfusion
Platelet transfusions are contraindicated in HIT because they provide additional substrate for thrombosis and can worsen thrombotic complications. 1, 6 Platelets should only be transfused if there is life-threatening bleeding or during high-risk invasive procedures. 6, 2
The pathophysiology of HIT involves antibody-mediated platelet activation leading to a prothrombotic state—adding more platelets fuels this process rather than helping it. 3
Monitoring and Dose Adjustment
Monitor activated partial thromboplastin time (aPTT) and adjust argatroban to maintain aPTT at 1.5 to 3 times baseline value. 4 Check aPTT 2 hours after starting infusion and after any dose adjustment. 3
Track platelet count daily to document recovery, which typically begins within 3-5 days of stopping heparin and starting alternative anticoagulation. 7, 8
Duration of Therapy
Continue argatroban until platelet count recovers to at least 150,000/μL, then transition to oral anticoagulation if long-term therapy is needed. 1, 2 For isolated HIT without thrombosis, continue anticoagulation for at least 4 weeks due to the extended thrombotic risk. 3
For HIT with thrombosis (HITTS), continue anticoagulation for 3 months, consistent with treatment of venous thromboembolism from other reversible provoking factors. 3
Transition to Oral Anticoagulation
Do not start warfarin until platelets have recovered to >150,000/μL as early warfarin initiation can cause venous limb gangrene in acute HIT. 1, 2 When starting warfarin, use low initial doses (maximum 5 mg) and overlap with argatroban for at least 5 days and until INR is therapeutic. 2, 8
Be aware that argatroban artificially elevates INR—21% of patients with INR >3.0 on combined therapy had subtherapeutic INR 4 hours after stopping argatroban. 3 The INR during cotherapy does not reflect warfarin effect alone. 3
Direct oral anticoagulants (DOACs) are acceptable alternatives to warfarin for long-term management and avoid the INR monitoring complexity. 1
Critical Pitfalls to Avoid
Never delay stopping heparin while waiting for antibody test results—the thrombotic risk is immediate and severe. 1, 2 In one study, 5 patients developed new thrombosis despite INR >4 during argatroban/warfarin cotherapy, while only 1 had major bleeding, demonstrating that thrombotic risk exceeds bleeding risk even with elevated INR. 8
Do not use prophylactic doses of alternative anticoagulants—therapeutic doses are mandatory even in isolated HIT without thrombosis due to the 30-50% risk of developing thrombosis. 3, 1
Avoid low molecular weight heparin (LMWH) as it cross-reacts with HIT antibodies in approximately 80-90% of cases. 3
Evidence Quality
The recommendation for argatroban is based on prospective cohort studies with historical controls showing moderate quality evidence for reduction in new thrombosis and very low quality evidence for mortality benefit. 3 Despite limitations in study design, the consistent benefit across multiple outcomes and the catastrophic consequences of untreated HIT support strong recommendations for immediate alternative anticoagulation. 3, 7