How should I manage an adult with heparin‑induced thrombocytopenia (HIT) and thrombosis, including immediate cessation of heparin, selection of an appropriate non‑heparin anticoagulant, and duration of therapy?

Management of Heparin-Induced Thrombocytopenia with Thrombosis (HITT)

Immediate Actions (Do Not Wait for Laboratory Confirmation)

Stop all heparin immediately and initiate therapeutic-dose non-heparin anticoagulation the moment HIT with thrombosis is suspected, without waiting for antibody test results. 1, 2, 3

• Discontinue every form of heparin exposure: intravenous heparin, subcutaneous heparin, heparin flushes, and heparin-coated catheters. 3, 4
• Remove all potential sources including line locks and arterial catheter flushes. 3
• Never use prophylactic-dose anticoagulation—therapeutic doses are mandatory even with thrombocytopenia because the thrombotic risk (30-50% without treatment) far exceeds bleeding risk. 1, 2, 4

Selection of Non-Heparin Anticoagulant

First-Line Agent Selection Based on Organ Function

For normal renal and hepatic function:

• Argatroban 2 mcg/kg/min continuous IV infusion, targeting aPTT 1.5-3 times baseline. 2, 3, 4
• Check aPTT 2 hours after starting and after each dose adjustment. 4

For severe renal impairment (CrCl <30 mL/min):

• Argatroban is the only recommended option because it undergoes hepatic metabolism. 2, 3, 4
• Use standard dosing (2 mcg/kg/min) as renal dysfunction does not affect clearance. 2

For severe hepatic impairment (Child-Pugh C) or cirrhosis:

• Reduce argatroban to 0.5 mcg/kg/min due to hepatic clearance. 2, 4
• Alternative options: bivalirudin, danaparoid, or fondaparinux. 2, 3

For patients requiring cardiac procedures or urgent surgery:

• Bivalirudin is preferred due to its shorter half-life (20-30 minutes vs. 40-50 minutes for argatroban). 2, 3
• Stop bivalirudin 2 hours before procedure; stop argatroban 4 hours before. 2, 4

Alternative Agents

Fondaparinux:

• Emerging option with less evidence than direct thrombin inhibitors but acceptable for stable patients. 2, 3
• Advantage: no monitoring required; disadvantage: subcutaneous administration. 3

Danaparoid:

• Requires anti-Xa monitoring with danaparoid-specific calibration. 2, 4
• Must use therapeutic IV doses, not prophylactic doses. 4
• Not recommended in severe renal failure. 3

Critical Pitfalls to Avoid

Do NOT:

• Wait for antibody test results before stopping heparin and starting alternative anticoagulation—the thrombotic risk is immediate. 2, 4
• Use low molecular weight heparin (LMWH) as it cross-reacts with HIT antibodies in 80-90% of cases. 4
• Give platelet transfusions unless life-threatening bleeding occurs, as they worsen thrombosis. 2, 3, 4
• Start warfarin during acute thrombocytopenia—it can cause venous limb gangrene. 2, 3, 4
• Use prophylactic-dose anticoagulation—this is the most dangerous error in HIT management. 1, 4

Duration of Anticoagulation

For HITT (HIT with thrombosis):

• Continue non-heparin anticoagulant at therapeutic doses until platelet count recovers to >150,000/μL. 2, 4
• Minimum total anticoagulation duration: 3 months for documented thrombosis. 2, 4

For isolated HIT (without thrombosis):

• Continue anticoagulation for minimum 4 weeks due to high thrombosis risk extending 2-4 weeks after treatment initiation. 2

Transition to Oral Anticoagulation

Timing:

• Wait until platelet count recovers to >150,000/μL or returns to baseline before starting vitamin K antagonists. 2, 3, 4
• Overlap parenteral anticoagulant with oral agent for minimum 5 days. 1, 2, 5

Preferred oral agents:

• Direct oral anticoagulants (DOACs) are acceptable alternatives to warfarin with advantages of fixed dosing and no monitoring. 2
• Rivaroxaban is the most studied DOAC in HIT: 15 mg twice daily until day 21 (or platelet recovery >150,000/μL), then 20 mg daily. 4
• Apixaban is an acceptable alternative with demonstrated safety (0/21 major bleeds in published series). 4

Comparative Effectiveness Data

Argatroban vs. discontinuing heparin alone:

• For HITT: 134 fewer deaths per 1,000 (RR 0.12) and 191 fewer thrombotic events per 1,000 (RR 0.45). 2
• For isolated HIT: 40 fewer deaths per 1,000 (RR 0.07) and 169 fewer thrombotic events per 1,000 (RR 0.29). 2

Special Considerations for Active Bleeding

Even with active bleeding, therapeutic anticoagulation is mandatory because the thrombotic risk of untreated HIT far exceeds bleeding risk. 4

• For high bleeding risk, argatroban or bivalirudin are preferred due to short half-lives allowing rapid reversal. 4
• Consider temporary dose reduction rather than prophylactic dosing, then escalate as bleeding stabilizes. 4
• Platelet transfusions should not be given unless life-threatening bleeding occurs. 4

Long-Term Management

• Document HIT diagnosis prominently in medical records. 3
• Avoid re-exposure to heparin, especially within 3 months of diagnosis. 3, 4
• For future anticoagulation needs, use oral anticoagulants (VKA or DOAC) or fondaparinux. 3
• Schedule follow-up with hematology within 3 months of diagnosis. 4