What is the treatment for heparin-induced thrombocytopenia (HIT)?

Treatment of Heparin-Induced Thrombocytopenia (HIT)

Immediately discontinue all heparin products and start a non-heparin anticoagulant at therapeutic doses without waiting for laboratory confirmation when HIT is suspected with intermediate or high clinical probability. 1

Initial Assessment and Immediate Actions

• Stop all heparin immediately including unfractionated heparin, low-molecular-weight heparin, heparin flushes, and heparin-coated catheters when the 4Ts score is ≥4 (intermediate or high probability) 1
• Do not wait for laboratory confirmation to initiate alternative anticoagulation, as the risk of thrombosis is immediate and severe 2
• If the 4Ts score is ≤3 (low probability), HIT is excluded and heparin can be continued while investigating other causes of thrombocytopenia 1

Choice of Alternative Anticoagulant

The selection depends primarily on renal and hepatic function:

For Normal Renal and Hepatic Function

Argatroban or lepirudin are the preferred agents, with danaparoid as an alternative option 2, 1:

• Argatroban: Start at 2 mcg/kg/min continuous IV infusion (maximum 10 mcg/kg/min) 3

  • Monitor with aPTT targeting 1.5-3 times baseline (not exceeding 100 seconds) 3
  • Check aPTT 2 hours after initiation and after any dose adjustment 3
  • Argatroban reduces death from thrombosis by 40 fewer deaths per 1,000 patients (RR 0.07) and prevents 169 fewer thrombotic events per 1,000 (RR 0.29) compared to discontinuing heparin alone 1

• Danaparoid: Administer at therapeutic IV doses with anti-Xa monitoring 1

  • Has the advantage of not affecting INR or aPTT, simplifying transition to warfarin 2
  • Shows lower in vitro cross-reactivity (10-40%) with HIT antibodies compared to LMWH 4

For Severe Renal Impairment (CrCl <30 mL/min)

Argatroban is the only recommended option because it is hepatically cleared 2, 1:

• Lepirudin has dramatically increased elimination half-life in renal failure and should be avoided 5
• Danaparoid has a 24-hour half-life and requires dose adjustment 5

For Severe Hepatic Impairment (Child-Pugh C)

Use bivalirudin, danaparoid, or fondaparinux 1:

• Argatroban is contraindicated as it is hepatically metabolized 1

For Urgent Cardiac Surgery or PCI

Bivalirudin is the preferred agent 2, 6:

• For PCI: Give 350 mcg/kg IV bolus over 3-5 minutes, then 25 mcg/kg/min infusion 3
• Target ACT >300 seconds (check 5-10 minutes after bolus) 3
• If ACT <300 seconds: give additional 150 mcg/kg bolus and increase infusion to 30 mcg/kg/min 3
• If ACT >450 seconds: decrease infusion to 15 mcg/kg/min 3
• Stop infusion 2 hours before surgical procedures (versus 4 hours for argatroban) 2, 6

Emerging Options with Less Evidence

Fondaparinux can be considered but has less supporting evidence than direct thrombin inhibitors 2, 1:

• Some experts switch from a DTI to fondaparinux once platelets recover (>150 × 10⁹/L) to facilitate warfarin transition 2
• Does not affect INR or aPTT monitoring 2

Direct oral anticoagulants (DOACs) have weak conditional support with advantages of fixed dosing and no monitoring required 1

Critical Management Pitfalls to Avoid

Do NOT Use Warfarin During Acute Thrombocytopenia

Warfarin can cause venous limb gangrene in patients with acute HIT and deep vein thrombosis 7, 8:

• Warfarin has a slow onset and can precipitate this devastating complication 4
• Only initiate warfarin after substantial platelet count recovery (>150 × 10⁹/L) 7, 8
• Use low initial doses with at least 5 days of overlapping therapy with alternative anticoagulant 7, 8
• Maintain alternative anticoagulant until platelet count normalizes 7

Monitoring Complications with Argatroban

Argatroban artificially elevates INR, complicating transition to warfarin 2, 3:

• 21% of patients with INR >3.0 on argatroban plus warfarin had subtherapeutic INR 4 hours after stopping argatroban 2
• Do not interpret INR as reflecting warfarin effect alone when co-administered with argatroban 2

Do NOT Use These Interventions

• Do not transfuse platelets in acute HIT unless life-threatening bleeding occurs 2
• Do not prescribe antiplatelet agents to treat acute HIT 2
• Do not use IV immunoglobulins as first-line treatment 2
• Do not insert inferior vena cava filters in acute HIT 2
• Do not use low-molecular-weight heparin due to high cross-reactivity rates (up to 100%) with HIT antibodies 4

Duration of Anticoagulation

For HIT with thrombosis (HITT): Continue anticoagulation for minimum 3 months, consistent with treatment of VTE from other reversible provoking risk factors 2, 1

For isolated HIT: Continue anticoagulation for 4 weeks due to high thrombosis risk extending 2-4 weeks after treatment initiation 2, 1:

• The risk of thrombosis remains elevated during this period even without documented thrombosis 2

Perioperative Management

Postpone elective surgery for at least 1 month after HIT diagnosis unless major vital or functional risk exists 2:

• For urgent surgery with acute HIT (<1 month), stop oral anticoagulant and use preoperative bridging with argatroban or bivalirudin 2
• Stop argatroban 4 hours before procedure; stop bivalirudin 2 hours before procedure 2
• Postoperatively, if prolonged anticoagulation needed and bleeding controlled, use fondaparinux or oral anticoagulant (VKA or DOAC) 2