What is the recommended treatment with Angiomax (bivalirudin) for patients with Heparin-Induced Thrombocytopenia (HIT)?

Bivalirudin (Angiomax) for Heparin-Induced Thrombocytopenia

Bivalirudin is FDA-approved and recommended as an alternative anticoagulant for HIT patients, with specific preference for those requiring percutaneous coronary intervention (PCI) or cardiac surgery, though argatroban remains the preferred first-line agent for most acute HIT cases, particularly in patients with renal insufficiency. 1

FDA-Approved Indications

Bivalirudin is specifically indicated as an anticoagulant for patients undergoing PCI, including those with HIT and heparin-induced thrombocytopenia with thrombosis syndrome (HITTS). 1

Clinical Scenarios Where Bivalirudin is Preferred

Cardiac Procedures

• For patients with acute HIT or subacute HIT requiring urgent cardiac surgery, bivalirudin is suggested over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C recommendation). 2
• For patients with subacute HIT B or remote HIT requiring PCI, bivalirudin is suggested over unfractionated heparin based on evidence showing reduced bleeding risk compared to heparin in non-HIT patients. 2

Renal Replacement Therapy

• In acute HIT patients receiving renal replacement therapy requiring anticoagulation to prevent dialysis circuit thrombosis, bivalirudin is suggested alongside argatroban and danaparoid as acceptable options. 2

Hepatic Impairment

• Bivalirudin can be used in patients with severe hepatic impairment (Child-Pugh C), where argatroban is contraindicated. 2

Dosing and Administration

Standard PCI Dosing

• 0.75 mg/kg IV bolus followed immediately by 1.75 mg/kg/hour IV infusion for the duration of the procedure. 1
• Assess activated clotting time (ACT) five minutes after bolus; administer additional 0.3 mg/kg bolus if needed. 1
• Consider extending infusion up to 4 hours post-procedure in ST-elevation MI patients. 1

Critical Illness with Organ Dysfunction

The standard dosing requires substantial reduction in critically ill patients:

• Hepatic dysfunction alone: 0.14 mg/kg/hour 3
• Renal dysfunction alone: 0.03-0.05 mg/kg/hour 3
• Combined hepatic and renal dysfunction: 0.03 mg/kg/hour (median dose) 3
• Continuous renal replacement therapy: 0.03-0.04 mg/kg/hour 3

Perioperative Management

• Stop infusion 2 hours before surgical procedures (compared to 4 hours for argatroban). 2
• For urgent surgery in acute HIT patients, bivalirudin is preferred for preoperative bridging due to its short half-life of approximately 25 minutes. 2, 4

Monitoring

Laboratory Parameters

• Target aPTT: 1.5-2.5 times baseline 3
• ACT monitoring during PCI procedures 1
• Alternative assays include ecarin clotting time (ECT), thrombin time (TT), and dilute TT for more precise monitoring. 4

Common Pitfall

Supratherapeutic aPTTs occur most frequently on days 1-2 when doses are highest, particularly in patients with organ dysfunction. 3 Dose adjustments should be made promptly based on aPTT monitoring.

Comparative Effectiveness

Versus Argatroban

• Bivalirudin reaches therapeutic aPTT faster (7 ± 8 hours vs 14 ± 15 hours) with more aPTT values within therapeutic range (84% vs 69%). 5
• Clinical outcomes including thromboembolic events, bleeding, and mortality are similar between the two agents. 5
• However, argatroban remains the only FDA-approved agent specifically for HIT treatment (bivalirudin is approved for PCI in HIT patients, not general HIT management). 6

Versus Heparin in Remote HIT

• In patients without HIT undergoing PCI, bivalirudin demonstrates lower major bleeding risk (OR 0.55; 95% CI 0.44-0.69) with similar ischemic event rates. 2
• Heparin is an acceptable alternative in subacute HIT B or remote HIT if bivalirudin is unavailable or institutional experience is lacking, with exposure limited to the intraprocedural setting only. 2

Safety Profile

Bleeding Risk

• Most common adverse reaction is bleeding (3.7%). 1
• The anticoagulant effect subsides approximately one hour after discontinuation due to short half-life. 1
• In critically ill patients with organ dysfunction, clinically significant bleeding did not occur when appropriately dosed. 3

Thrombotic Risk

• Increased risk of thrombus formation, including fatal outcomes, has been reported with gamma brachytherapy. 1
• Thrombosis occurred in only 6% of critically ill patients receiving bivalirudin for HIT. 3

Contraindications

• Significant active bleeding 1
• Hypersensitivity to bivalirudin or its components 1

Availability Considerations

Bivalirudin is widely used for PCI in the United States but not internationally, and is currently unavailable in France, though generics may become available in other European countries. 2 This geographic variability in availability influences treatment decisions, with argatroban or other alternatives preferred when bivalirudin is unavailable or institutional experience is lacking. 2