What is the management of heparin-induced thrombocytopenia (HIT)?

Management of Heparin-Induced Thrombocytopenia (HIT)

Immediately discontinue all forms of heparin (including flushes and heparin-coated catheters) and start therapeutic-dose non-heparin anticoagulation without waiting for laboratory confirmation when HIT is suspected with intermediate or high clinical probability. 1, 2

Initial Risk Stratification Using the 4T Score

Calculate the 4T score to determine pre-test probability before any other intervention: 1, 2

• Low probability (4T ≤3): HIT can be excluded—continue heparin with close platelet monitoring and pursue alternative causes of thrombocytopenia 1, 2

• Intermediate probability (4T = 4-5): Stop all heparin immediately, initiate therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing 1, 2

• High probability (4T ≥6): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing—do not wait for results before treating 1, 2

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

Immediate Management Actions

Stop all heparin exposure including subcutaneous heparin, heparin flushes, heparin-coated catheters, and heparin locks. 1, 2 This must occur immediately upon suspicion—delaying for laboratory confirmation increases thrombotic risk substantially. 1

Start therapeutic-dose non-heparin anticoagulation immediately, even if thrombosis is not present, because HIT carries extremely high thrombotic risk due to marked thrombin generation. 1, 2 Prophylactic doses are insufficient and should never be used. 1, 2

Avoid platelet transfusions as they may worsen thrombosis in HIT patients. 1, 2

Alternative Anticoagulant Selection

Argatroban (Direct Thrombin Inhibitor)

Argatroban is the preferred agent for patients with renal impairment (CrCl <30 mL/min) because it is hepatically metabolized. 1, 2, 3

• Dosing for HIT without hepatic impairment: Start at 2 mcg/kg/min as continuous IV infusion 1, 3
• Monitor aPTT to maintain 1.5-3 times baseline value 1, 3
• For severe hepatic impairment: Reduce starting dose and titrate carefully 1, 3
• For PCI in HIT patients: Start at 25 mcg/kg/min with a bolus of 350 mcg/kg over 3-5 minutes; check ACT 5-10 minutes after bolus (target >300 seconds) 3

Argatroban interferes with INR, making transition to warfarin more complex. 4

Bivalirudin (Direct Thrombin Inhibitor)

Bivalirudin has a shorter half-life (20-30 minutes) and is useful for procedures requiring short-acting anticoagulation. 1, 2

• Contraindicated in severe renal failure (CrCl <30 mL/min) 1
• Preferred in severe hepatic impairment (Child-Pugh C) 1
• Dosing: 0.15-0.25 mg/kg/hour IV infusion, targeting aPTT 1.5-2.5 times control 1

Fondaparinux (Factor Xa Inhibitor)

Fondaparinux is an acceptable option for stable patients without severe renal or hepatic impairment and does not require specific monitoring. 1, 2, 5

• Prophylactic doses appear effective if no indication for full anticoagulation exists 5
• Has been shown to have similar effectiveness and safety as argatroban and danaparoid in propensity-matched studies 5
• Can be used even in severe renal impairment based on emerging evidence, though this requires careful consideration 6

Danaparoid (Heparinoid)

Danaparoid requires monitoring of anti-Xa activity with specific calibration and should not be used at prophylactic doses for acute HIT. 1 Curative IV doses with anti-Xa monitoring are required. 1

Laboratory Testing Strategy

For intermediate probability (4T = 4-5): 1

• Perform anti-PF4 antibody testing (ELISA or chemiluminescent assay) while simultaneously starting alternative anticoagulation
• If anti-PF4 antibodies are positive, perform functional test (serotonin release assay or HIPA test) to confirm diagnosis
• If anti-PF4 antibodies are negative, HIT is excluded and heparin can be resumed with close platelet monitoring

For high probability (4T ≥6): 1

• Perform anti-PF4 antibody testing but do not delay treatment
• Functional testing should follow if immunoassay is positive

Transition to Oral Anticoagulation

Wait for platelet count recovery (>150,000/μL or return to baseline) before transitioning to vitamin K antagonists (VKAs) to avoid venous limb gangrene. 1, 2

• Overlap parenteral anticoagulant with oral agent for at least 5 days 1, 2
• Direct oral anticoagulants (DOACs) are acceptable alternatives to warfarin for long-term anticoagulation 1
• Avoid VKAs in the acute phase of HIT as they can cause venous limb gangrene 1, 2

Perioperative Management

For acute HIT (<1 month): 1, 2

• Postpone elective surgery beyond the first month if possible
• If surgery cannot be delayed, use short-acting agents (argatroban or bivalirudin)
• Stop argatroban 4 hours before procedure; stop bivalirudin 2 hours before procedure 2

For cardiac surgery in patients with history of HIT: 1

• Systematically perform ELISA for anti-PF4 antibodies before surgery
• If antibodies are negative, brief heparin re-exposure during cardiopulmonary bypass may be tolerated with strict avoidance pre- and postoperatively 4, 7
• If antibodies are positive, use bivalirudin or argatroban for anticoagulation during bypass 1, 7

Special Clinical Situations

Severe HIT (massive PE, extensive/arterial thrombosis, venous gangrene, consumption coagulopathy): Prefer argatroban or bivalirudin with strict biological monitoring due to short half-lives and reversibility. 1

Severe renal impairment (CrCl <30 mL/min): Argatroban is the only recommended agent. 1, 2

Severe hepatic impairment (Child-Pugh C): Use bivalirudin, danaparoid, or fondaparinux. 1

Critical Pitfalls to Avoid

• Never delay stopping heparin while waiting for laboratory results if clinical suspicion is intermediate or high 1, 2
• Never use prophylactic doses of alternative anticoagulants—therapeutic doses are mandatory even without thrombosis 1, 2
• Never give platelet transfusions as they worsen thrombosis 1, 2
• Never start VKAs before platelet recovery due to risk of venous limb gangrene 1, 2
• Never insert an inferior vena cava filter in acute HIT due to increased thrombotic risk 2
• Never prescribe oral antiplatelet agents alone to treat acute HIT as they do not effectively prevent thrombosis 2

Long-term Management

• Document HIT diagnosis prominently in medical records and provide patient with documentation 1, 2
• Avoid re-exposure to heparin, especially within 3 months of HIT diagnosis 1, 2
• Consider extended anticoagulation (3-6 months) depending on clinical situation 1, 2
• Schedule follow-up with hematology within 3 months of diagnosis 1
• For future anticoagulation needs, use oral anticoagulants (VKA or DOAC) or fondaparinux 1, 2