Bentracimab for Surgical and Perioperative Bleeding: Clinical Efficacy, Emerging Safety Concerns, and Implementation...

Perioperative and surgical bleeding in patients on ticagrelor therapy remains a clinical challenge, with many patients undergoing urgent procedures experiencing severe bleeding. Ticagrelor is widely used in cardiovascular disease management. A notable proportion of patients undergoing percutaneous coronary intervention (PCI) later require surgical procedures within two years, creating significant challenges in perioperative care, including increased morbidity, the need for transfusions, and delays in life-saving surgery. These challenges are related to the reversible nature of P2Y₁₂ inhibition by ticagrelor and the presence of its circulating active metabolite. Together, these factors contribute to sustained platelet inhibition and reduce the effectiveness of non-specific reversal strategies. Platelet transfusion and supportive care have shown limited effectiveness, largely due to rapid re-inhibition of transfused platelets by circulating ticagrelor and its active metabolite. Bentracimab (PB2452), a high-affinity humanized monoclonal antibody fragment, was developed to bind ticagrelor and its active metabolite, thereby reversing platelet inhibition. This narrative review integrates available preclinical, translational, and clinical data assessing the efficacy, safety, and perioperative use of bentracimab in ticagrelor-associated bleeding in the setting of urgent surgery. In early-phase studies and the pivotal phase 3 REVERSE-IT trial, bentracimab rapidly restored platelet function, with effects observed within minutes and sustained for up to 24 hours. Pharmacodynamic reversal of platelet inhibition was consistent. Clinical outcomes, such as effective hemostasis, were achieved in a high proportion of patients, as reported in most available studies, supporting its potential use in urgent surgical settings. Short-term safety profiles appear promising, with low rates of infusion reactions and no clear evidence of prothrombotic effects in early-phase trials. However, thrombotic events have been observed in high-risk clinical scenarios, although these have not been definitively attributed to bentracimab. This warrants cautious interpretation, given limited follow-up and the absence of comparator trials. Current evidence is derived mainly from single-arm and early-phase studies. Randomized comparative data are lacking, and long-term safety, including thrombotic risk after reversal, remains unclear. Additional challenges include cost, access, and integration into perioperative care pathways. Compared to non-specific reversal strategies such as platelet transfusion and supportive care, bentracimab offers rapid and targeted neutralization of ticagrelor, with restoration of platelet function. Overall, bentracimab shows promising potential for integration into surgical and perioperative bleeding management protocols, pending further comparative studies and long-term outcome data.