What is the treatment for Heparin-Induced Thrombocytopenia (HIT)?

Treatment of Heparin-Induced Thrombocytopenia (HIT)

Immediately discontinue all heparin (including flushes and heparin-coated catheters) 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 Management Algorithm

Step 1: Calculate Pre-Test Probability (4Ts Score)

• If 4Ts ≤3 (low probability): HIT is excluded; continue heparin and investigate other causes of thrombocytopenia 1
• If 4Ts = 4-5 (intermediate) or ≥6 (high): Stop all heparin immediately and initiate alternative anticoagulation before laboratory results return 1

Step 2: Choose Alternative Anticoagulant

The choice depends on organ function and clinical scenario:

For Normal Renal and Hepatic Function:

• Argatroban (direct thrombin inhibitor): 2 mcg/kg/min continuous IV infusion 2
• Bivalirudin (direct thrombin inhibitor): preferred for PCI or urgent cardiac surgery 3
• Danaparoid (heparinoid): therapeutic IV doses with anti-Xa monitoring 1
• Fondaparinux: emerging option but less evidence than DTIs 1

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

• Argatroban is the only recommended option 1, 4
• Danaparoid is contraindicated as first-line 1

For Severe Hepatic Impairment (Child-Pugh C):

• Bivalirudin, danaparoid, or fondaparinux 1
• Argatroban is contraindicated 1, 4

For Moderate Hepatic Impairment (Child-Pugh B):

• Argatroban can be used with dose reduction to 0.5 mcg/kg/min 4

Step 3: Monitoring

For Argatroban:

• Target aPTT 1.5-3 times baseline (not exceeding 100 seconds) 2
• Check aPTT 2 hours after initiation and after any dose change 2
• Maximum dose: 10 mcg/kg/min 2

Critical Pitfall: When argatroban is combined with warfarin, the INR is artificially elevated and does not reflect warfarin effect alone. 21% of patients with INR >3.0 on combination therapy had subtherapeutic INR 4 hours after stopping argatroban. 1

For PCI with Argatroban:

• Initial bolus: 350 mcg/kg IV over 3-5 minutes 2
• Infusion: 25 mcg/kg/min 2
• Target ACT >300 seconds (check 5-10 minutes post-bolus) 2

Step 4: Transition to Warfarin

Do not start warfarin during acute thrombocytopenia - this can cause venous limb gangrene in patients with HIT-associated DVT. 5, 6

Warfarin initiation criteria:

• Wait until platelet count substantially recovers (>150 × 10⁹/L) 4
• Use low initial warfarin doses 5
• Overlap with alternative anticoagulant for minimum 5 days AND until INR is therapeutic 4, 5
• Continue alternative anticoagulant until platelet count normalizes 5

Step 5: Duration of Anticoagulation

For HIT with thrombosis (HITT):

• Continue anticoagulation for minimum 4 weeks (can use warfarin or alternative agent) 1
• If treating VTE secondary to HIT, consider 3 months total (HIT is a reversible provoking factor) 1

For isolated HIT (no thrombosis):

• Continue anticoagulation for 4 weeks due to high thrombosis risk extending 2-4 weeks after treatment initiation 1

Emerging Treatment Options

Direct Oral Anticoagulants (DOACs):

• Not FDA-approved for HIT but gaining acceptance 1
• International survey shows 74.5% acceptance for rivaroxaban and 73.5% for apixaban even before platelet recovery 1
• American Society of Hematology provides weak conditional support 1
• Advantages: fixed dosing, no monitoring required, lower bleeding risk than parenteral agents 1
• Consider in resource-limited settings where DTIs are unavailable or monitoring is challenging 1

Intravenous Immunoglobulin (IVIg):

• Strong expert acceptance (>83%) for spontaneous autoimmune HIT, persistent HIT, and treatment-refractory HIT 1
• Consider when thrombocytopenia persists >1 week after heparin discontinuation 1

Critical Pitfalls to Avoid

1. Never use LMWH as alternative anticoagulation - up to 100% cross-reactivity with HIT antibodies 6
2. Never delay treatment waiting for laboratory confirmation when clinical probability is intermediate/high 1
3. Never start warfarin during acute thrombocytopenia - risk of venous limb gangrene 5, 6
4. Never misinterpret INR on argatroban - 70% of premature argatroban discontinuations led to recurrent thrombosis 1
5. Never use prophylactic doses of alternative anticoagulants - therapeutic doses required even for isolated HIT 1

Comparative Effectiveness Data

Argatroban vs. discontinuing heparin alone for HITT:

• 134 fewer deaths per 1,000 (RR 0.12) 1
• 191 fewer thrombotic events per 1,000 (RR 0.45) 1

Argatroban vs. discontinuing heparin alone for isolated HIT:

• 40 fewer deaths per 1,000 (RR 0.07) 1
• 169 fewer thrombotic events per 1,000 (RR 0.29) 1

These data demonstrate that simply stopping heparin is insufficient - active anticoagulation with alternative agents significantly reduces mortality and thrombosis. 1