PB1005 - Recombinant activated factor VII for antithrombotic reversal of FXIa inhibitor milvexian in patient presented with spontaneous intracranial hemorrhage

Background: Milvexian is a selective FXa inhibitor undergoing investigation for prevention and treatment of thromboembolism. However, the reversal strategies in patients with FXI/FXIa inhibitor associated bleeding remains unclear.

Aims: To investigate the efficacy and safety of recombinant activated factor VII (rFVIIa) for milvexian reversal

Methods: A 65-year-old woman experienced an inferior wall myocardial infarction. As part of a clinical trial, she was prescribed milvexian (1 tablet orally twice daily), along with aspirin and ticagrelor ). Two weeks later, she was diagnosed with recurrent non-ST-segment elevation myocardial infarction. She received enoxaparin, aspirin, and clopidogrel. Ten hours later, the patient was found to have acute right frontal lobar hemorrhage, with impending right uncal brain herniation.

Results: At the time of presentation, the patient was comatose. Laboratory results revealed a hemoglobin level of 10.9 g/dL, a white blood count of 17.7 x 10^9/L, and a platelet count of 761 x 10^9/L. BUN was elevated at 36 mg/dL, and the creatinine level was 1.59 mg/dL. PT was 12.2 seconds (9.9-12.3), the aPTT was 54.7 seconds (28.8-36.4), and the factor XI (FXI) assay was 42.6 U/dL (65-130).
The patient received recombinant factor VIIa (rFVIIa) at a dose of 30 μg/kg and tranexamic acid at a dose of 1,000 mg intravenously. ROTEM was performed, revealing a shortening of clotting time and clot formation time after the administration of rFVIIa and tranexamic acid. Maximum clot firmness was observed in the INTEM assay after the administration of rFVIIa. Unfortunately, the clinical course deteriorated, and the patient passed away within 24 hours of hospital admission.

Conclusion(s): There is limited evidence regarding strategies to reverse the antithrombotic effect of FXI/FXIa inhibitors. Adopting strategies from patients with inherited FXI deficiency, which is low-dose rFVIIa combined with tranexamic acid, appears to be a reasonable treatment option. Urgent prospective studies on the reversal of FXI/FXIa inhibitors are needed.