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

Management of Heparin-Induced Thrombocytopenia (HIT)

Immediate Action Required

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

Risk Stratification Using 4T Score

Calculate the 4T score to determine pre-test probability:

• Low probability (≤3 points): HIT can be excluded, continue heparin with close platelet monitoring 1, 2
• Intermediate probability (4-5 points): Stop all heparin immediately, initiate therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing 1, 2
• High probability (≥6 points): Stop all heparin immediately, start therapeutic-dose alternative anticoagulation, and perform anti-PF4 antibody testing—do not wait for results before treating 1, 2

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

Alternative Anticoagulation Selection

First-Line Agents

Argatroban (preferred in renal impairment):

• Starting dose: 2 mcg/kg/min as continuous IV infusion 1, 3
• Monitor aPTT to maintain 1.5-3 times baseline value 1, 3
• Preferred agent when creatinine clearance <30 mL/min as it is hepatically metabolized 1, 2
• Reduce dose in moderate-to-severe hepatic impairment 3

Bivalirudin:

• Starting dose: 0.15-0.25 mg/kg/hour IV infusion 1
• Monitor aPTT to maintain 1.5-2.5 times control value 1
• Shorter half-life (20-30 minutes) makes it useful for procedures requiring short-acting anticoagulation 1
• Contraindicated in severe renal failure (CrCl <30 mL/min) 1

Fondaparinux:

• Option for stable patients without severe renal or hepatic impairment 2
• Does not require specific monitoring 2
• Prophylactic doses appear effective if no indication for full anticoagulation exists 4
• Research shows similar effectiveness and safety as argatroban and danaparoid 4, 5

Danaparoid:

• Requires monitoring of anti-Xa activity with specific calibration 1
• Must use curative IV doses, not prophylactic doses 1
• Not recommended in severe renal failure 2

Organ-Specific Selection Algorithm

• Severe renal impairment (CrCl <30 mL/min): Argatroban is the only recommended agent 1, 2
• Severe hepatic impairment (Child-Pugh C): Bivalirudin, danaparoid, or fondaparinux 1, 2
• Normal renal and hepatic function: Any of the above agents 1
• Severe HIT (massive PE, extensive thrombosis, venous gangrene): Prefer argatroban or bivalirudin with strict biological monitoring 1, 2

Critical Management Principles

Therapeutic doses are mandatory even without thrombosis due to the high thrombotic risk in HIT—prophylactic doses are insufficient 1, 2

Do not give platelet transfusions as they may worsen thrombosis 1, 2

Avoid vitamin K antagonists (warfarin) in the acute phase as they can cause venous limb gangrene 1, 2

Transition to Oral Anticoagulation

• Wait for platelet count recovery (>150,000/μL or return to baseline) before transitioning to vitamin K antagonists 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

Perioperative Management

For acute HIT (<1 month from diagnosis):

• Postpone elective surgery beyond the first month if possible 1, 2
• If surgery cannot be delayed, use short-acting agents (argatroban or bivalirudin) 1, 2
• Stop argatroban 4 hours before procedure; stop bivalirudin 2 hours before procedure 2

For cardiac surgery in patients with HIT history:

• Systematically perform ELISA for anti-PF4 antibodies before surgery 1
• Two strategies: combination of IV antiplatelet agent with unfractionated heparin, or use of thrombin inhibitor (bivalirudin or argatroban) 1

Laboratory Testing Strategy

• For intermediate or high probability, perform anti-PF4 antibody testing (ELISA or chemiluminescent tests have high sensitivity and negative predictive value but lower specificity) 1
• If anti-PF4 antibodies are positive with intermediate probability, perform functional test (serotonin release assay or HIPA test) to confirm diagnosis 1
• If anti-PF4 antibodies are negative with intermediate probability, HIT is excluded and heparin can be resumed with close platelet monitoring 1

Long-Term Management

• Document HIT diagnosis in medical records and provide patient with documentation 1, 2
• Avoid re-exposure to heparin, especially within 3 months of HIT diagnosis 1, 2
• For future anticoagulation needs, use oral anticoagulants (VKA or DOAC) or fondaparinux 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

Common Pitfalls to Avoid

• Never delay discontinuation of 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 required even without thrombosis 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
• Never use IV immunoglobulins as first-line treatment for acute HIT 2