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: low (≤3 points), intermediate (4-5 points), or high (≥6 points). 1, 2

• For low probability (4T ≤3): HIT can be excluded, continue heparin with close platelet monitoring every 2-3 days, and pursue alternative causes of thrombocytopenia. 1, 2

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

• For 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

• In post-cardiac surgery patients, recognize that the 4T score is less reliable; a "biphasic" pattern in platelet count evolution strongly suggests HIT. 1

Immediate Management Actions

• Remove all heparin sources including subcutaneous heparin, heparin flushes, heparin-coated catheters, and heparin locks. 1, 2

• Start therapeutic-dose non-heparin anticoagulation immediately, even if thrombosis is not present, because HIT carries a high thrombotic risk (up to 50% develop new thrombosis). 1, 2

• Do not give platelet transfusions, as they may worsen thrombosis in HIT patients. 1, 2

• Do not use prophylactic doses of alternative anticoagulants—therapeutic doses are mandatory even without documented thrombosis. 1, 2

Alternative Anticoagulant Selection

For Normal Renal and Hepatic Function:

• Argatroban is a recommended first-line option: start at 2 mcg/kg/min as continuous IV infusion, monitor aPTT to maintain 1.5-3 times baseline value. 1, 3

• Bivalirudin is an alternative with a shorter half-life (20-30 minutes): start at 0.15-0.25 mg/kg/hour IV infusion, monitor aPTT to maintain 1.5-2.5 times control value. 1

• Fondaparinux is an option for stable patients: does not require specific monitoring and has demonstrated similar effectiveness and safety as argatroban and danaparoid. 1, 4

• Direct oral anticoagulants (DOACs) are acceptable alternatives for stable patients without severe organ dysfunction. 1

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

• Argatroban is the only recommended agent because it is hepatically metabolized and does not accumulate in renal failure. 1, 2, 3

• Avoid bivalirudin as it is contraindicated in severe renal failure. 1

• Fondaparinux can be used cautiously with dose adjustment, though data are limited; one small study showed safety even in severe renal impairment. 5

For Severe Hepatic Impairment (Child-Pugh C):

• Bivalirudin, danaparoid, or fondaparinux may be used. 1

• Reduce argatroban dose and titrate carefully if used in hepatic impairment. 1, 3

For Severe HIT (massive PE, extensive thrombosis, venous gangrene):

• Prefer argatroban or bivalirudin with strict biological monitoring due to their short half-lives and reversibility. 1, 2

Laboratory Testing Strategy

• Order anti-PF4 antibody testing (ELISA or chemiluminescent immunoassay) immediately for intermediate or high probability cases, but do not delay treatment while awaiting results. 1, 2

• If anti-PF4 antibodies are positive with intermediate probability, perform a 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

Monitoring During Treatment

• For argatroban: Monitor aPTT 2 hours after starting infusion and after any dose adjustment, targeting 1.5-3 times baseline value. 1, 3

• For danaparoid: Monitor anti-Xa activity with a specific calibration curve for danaparoid. 1

• Monitor platelet count daily until recovery to >150,000/μL or return to baseline. 1, 2

• Monitor hemoglobin and hematocrit for signs of bleeding. 1

Transitioning to Oral Anticoagulation

• Wait for platelet count recovery (>150,000/μL or return to baseline) before starting vitamin K antagonists (VKAs), as they can potentially cause venous limb gangrene in acute HIT. 1, 2

• Overlap parenteral anticoagulant with oral agent for at least 5 days before discontinuing parenteral therapy. 1, 2

• Direct oral anticoagulants (DOACs) are acceptable alternatives to warfarin for long-term anticoagulation and do not carry the same risk of venous limb gangrene. 1

Perioperative Management

• For acute HIT (<1 month): Postpone elective surgery beyond the first month if possible to minimize thrombotic complications. 1, 2

• If surgery cannot be delayed: Use short-acting agents like argatroban (stop 4 hours before procedure) or bivalirudin (stop 2 hours before procedure). 1, 2

• For cardiac surgery in patients with history of HIT: Systematically perform ELISA for anti-PF4 antibodies before surgery; if negative, brief heparin re-exposure during cardiopulmonary bypass may be tolerated with strict avoidance pre- and postoperatively. 1

• For PCI in patients with or at risk for HIT: Use argatroban at 25 mcg/kg/min with a bolus of 350 mcg/kg over 3-5 minutes; check ACT 5-10 minutes after bolus (proceed if ACT >300 seconds). 3

Common Pitfalls to Avoid

• Do not delay stopping heparin while waiting for laboratory confirmation if clinical suspicion is intermediate or high. 1, 2

• Do not use prophylactic doses of alternative anticoagulants—therapeutic doses are required even without documented thrombosis. 1, 2

• Do not start warfarin in the acute phase before platelet recovery, as it can cause venous limb gangrene. 1, 2

• Do not give platelet transfusions unless life-threatening bleeding occurs, as they worsen thrombosis. 1, 2

• Do not prescribe oral antiplatelet agents alone to treat acute HIT, as they do not effectively prevent thrombosis. 2

• Do not insert an inferior vena cava filter in the acute phase of HIT due to increased thrombotic risk. 2

Long-term Management

• Document HIT diagnosis prominently in medical records with laboratory results. 1

• Provide patient with documentation of their HIT diagnosis and laboratory results. 1

• Schedule follow-up with hematology within 3 months of diagnosis. 1

• Avoid re-exposure to heparin, especially within 3 months of HIT diagnosis; use oral anticoagulants (VKA or DOAC) or fondaparinux for future anticoagulation needs. 1, 2

• Consider extended anticoagulation (3-6 months) depending on the clinical situation and presence of thrombosis. 1, 2