What is the appropriate management of suspected heparin‑induced thrombocytopenia?

Management of Suspected Heparin-Induced Thrombocytopenia (HIT)

Immediately discontinue all heparin exposure (including flushes and heparin-coated catheters) and start therapeutic-dose non-heparin anticoagulation without waiting for laboratory confirmation if clinical suspicion is intermediate or high. 1

Initial Risk Assessment Using 4T Score

Calculate the 4T score to determine pre-test probability, which evaluates thrombocytopenia severity, timing of platelet fall, presence of thrombosis, and other causes of thrombocytopenia 1:

• Low probability (4T ≤3): HIT can be excluded; continue heparin with close platelet monitoring and pursue alternative diagnoses 1
• Intermediate probability (4T = 4-5): Stop all heparin immediately, initiate therapeutic-dose alternative anticoagulation, and send anti-PF4 antibody testing 1
• High probability (4T ≥6): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and send anti-PF4 antibody testing—do not wait for results before treating 1

Critical pitfall: The 4T score is less reliable in post-cardiac surgery patients, where a "biphasic" platelet count pattern strongly suggests HIT 1

Immediate Anticoagulation Management

First-Line Agent Selection

Argatroban is the preferred first-line agent for most patients with suspected HIT 1, 2:

• Standard dosing: Start at 2 mcg/kg/min as continuous IV infusion 3, 1
• Reduced dosing (0.5 mcg/kg/min) for patients with moderate/severe hepatic impairment, heart failure, multiple organ dysfunction, or post-cardiac surgery 1, 4
• Monitor aPTT 2 hours after starting and after dose adjustments, targeting 1.5-3 times baseline 1, 3

Rationale: Argatroban reduces new thrombosis (RR 0.29) and death from thrombosis compared to stopping heparin alone 1. It is the only alternative suitable for severe renal impairment (CrCl <30 mL/min) due to hepatic metabolism 1, 2

Alternative Agents

Bivalirudin is an acceptable alternative with shorter half-life (20-30 minutes), useful when rapid reversibility is needed 1:

• Contraindicated in severe renal failure (CrCl <30 mL/min) 1
• Can be stopped 2 hours before urgent procedures 1

Danaparoid requires anti-Xa monitoring with specific calibration and should be used at curative IV doses (not prophylactic) 1, 4

Fondaparinux is acceptable but requires subcutaneous injection and is contraindicated in severe renal failure 1

Critical Management Principles

Therapeutic Dosing is Mandatory

Never use prophylactic doses—therapeutic anticoagulation is required even in isolated HIT without thrombosis, as 30-50% of untreated patients develop thrombosis 1, 2. This applies even with active bleeding, as the thrombotic risk far exceeds bleeding risk 1.

Avoid Common Pitfalls

• Do not delay treatment while waiting for antibody test results—the thrombotic risk is immediate and severe 1
• Do not use LMWH as it cross-reacts with HIT antibodies in 80-90% of cases 1
• Do not give platelet transfusions unless life-threatening bleeding occurs, as they worsen thrombosis 1
• Do not start warfarin until platelet count recovers to >150,000/μL, as it can cause venous limb gangrene in acute HIT 1, 2

Laboratory Testing Strategy

Send anti-PF4 antibody testing immediately but do not delay treatment 1, 2:

• If anti-PF4 antibodies are positive with intermediate probability: perform functional test (serotonin release assay or HIPA) to confirm diagnosis 1
• If anti-PF4 antibodies are negative with intermediate probability: HIT is excluded and heparin can be resumed with close monitoring 1

Transition to Oral Anticoagulation

Wait until platelet count recovers to >150,000/μL before transitioning 1, 2:

Preferred oral agents 1:

• Rivaroxaban: 15 mg twice daily until day 21 (or platelet recovery), then 20 mg daily for ≥3 months (most studied DOAC in HIT with 0/49 major bleeds) 1
• Apixaban: Acceptable alternative with 0/21 major bleeds and 0/21 recurrent thrombosis in published series 2

If warfarin is selected 2:

• Overlap with argatroban for at least 5 days 2
• Use low initial doses 2
• Continue argatroban until platelet count normalizes 2

Duration of Anticoagulation

• Isolated HIT without thrombosis: Minimum 4 weeks 1
• HIT with thrombosis (HITTS): Minimum 3 months 1, 2

Special Situations

Cardiac Surgery in Acute/Subacute HIT (<3 months)

Define perioperative anticoagulation protocol in multidisciplinary consultation (anesthesiologist, surgeon, hematologist) 4:

• Postpone surgery ideally >3 months after HIT diagnosis, or at least >1 month after thrombotic complication 4
• Perform ELISA for anti-PF4 antibodies: if negative, short-term heparin re-exposure is possible 4
• If anti-PF4 antibody titer is significant (ELISA OD >1): Use IV antiplatelet agent (tirofiban or cangrelor) + UFH, or direct thrombin inhibitor (bivalirudin or argatroban) 4
• For urgent surgery: Favor IV antiplatelet + UFH combination 4

Severe Renal and Hepatic Impairment

Argatroban is the only option for severe renal impairment (CrCl <30 mL/min) 1:

• Start at 0.5 mcg/kg/min in cirrhosis due to hepatic clearance 1
• Monitor aPTT every 2 hours initially, targeting 1.5-3 times baseline 1