What is the recommended approach for emergency reversal of Brilinta (ticagrelor) in a patient requiring urgent surgery?

Emergency Reversal of Ticagrelor for Urgent Surgery

For emergency reversal of ticagrelor in patients requiring urgent surgery, discontinue ticagrelor for at least 24 hours before surgery, and consider bentracimab (PB2452) if available, as it provides immediate and sustained reversal of ticagrelor's antiplatelet effects.

Current Guideline Recommendations

Timing of Surgery After Ticagrelor Discontinuation

• Elective surgery: Discontinue ticagrelor at least 5 days before surgery 1
• Urgent surgery: Discontinue ticagrelor for at least 24 hours before surgery to reduce major bleeding complications 1
• Intracranial neurosurgery: Requires longer discontinuation period (7 days) due to higher bleeding risk 1

Reversal Strategies for Urgent Surgery

1. Specific Reversal Agent

• Bentracimab (PB2452): A monoclonal antibody that specifically binds to ticagrelor and its active metabolite
  • Provides rapid reversal within 5-10 minutes of administration 2
  • Sustained effect for more than 24 hours
  • Achieves hemostasis in >90% of patients requiring urgent surgery 2
  • Currently in clinical trials but shows promising results for emergency situations

2. Platelet Transfusion

• Limited efficacy: Unlike with aspirin or clopidogrel, platelet transfusion has limited effectiveness for ticagrelor reversal 3, 4
• Dosing considerations: If used, higher doses may be required
  • The equivalent of six apheresis platelet units produced only 50% relative reversal at 10 hours after the last ticagrelor dose 3
  • Near complete reversal (>90%) was achieved at 24 hours with high-dose platelet transfusion 3

3. Other Potential Strategies

• Human albumin supplementation: May help bind free ticagrelor in plasma 5
• Hemadsorption: Experimental technique to remove ticagrelor from circulation 5

Decision Algorithm for Urgent Surgery

1. Assess time since last ticagrelor dose:

   • If >72 hours: Proceed with surgery (most patients will have sufficient platelet function recovery) 1, 4
   • If 24-72 hours: Consider platelet function testing if available
   • If <24 hours: Highest bleeding risk; consider specific reversal strategies

2. If surgery cannot be delayed for 24 hours:

   • Use bentracimab if available 2
   • If bentracimab unavailable, consider platelet transfusion (recognizing limited efficacy) 3

3. Intraoperative management:

   • Implement blood conservation strategies
   • Consider antifibrinolytic agents (e.g., tranexamic acid)
   • Be prepared for increased transfusion requirements

Important Considerations and Caveats

• Individual variability: There is significant interindividual variability in platelet function recovery after ticagrelor discontinuation 4

  • At 72 hours post-discontinuation, 25% of patients still had inadequate platelet function recovery 4

• Thrombotic risk: Rapid reversal of antiplatelet therapy carries a risk of thrombotic events (approximately 5% with bentracimab) 2

• Monitoring: If available, platelet function testing (e.g., VerifyNow P2Y12 assay) can help guide timing of surgery and need for additional reversal strategies

• Balancing risks: The decision to reverse ticagrelor must balance the risk of surgical bleeding against the risk of thrombotic events, particularly in patients with recent stent placement

• Avoid bridging: Guidelines recommend against bridging with heparin or NSAIDs when discontinuing antiplatelet therapy 1

The optimal approach depends on the urgency of surgery, bleeding risk of the procedure, and thrombotic risk of the patient. For truly emergent surgery where even 24 hours of delay is not possible, bentracimab offers the most promising solution if available.