Factor XI 1,000unit powder and solvent for solution for infusion vials

IntroductionFactor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing the role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD).MethodsWe systematically searched Embase, MEDLINE, and ClinicalTrials.gov for randomized controlled trials evaluating FXI/XIa inhibitors in patients with ESKD on HD, without restricting inclusion to specific comparators or indications. Interventional treatment arms were pooled, and study results were synthesized by fitting random-effects models, calculating odds ratios (ORs) and 95% confidence intervals (CIs).ResultsFive phases 2 studies encompassing 1270 participants were identified, investigating gruticibart, IONIS-FXIRx, osocimab, or fesomersen in the general HD population and using placebo as a comparator. Four studies were fully published and included in the meta-analysis. Use of FXI/XIa inhibitors was associated with an OR of 0.80 (95% CI = 0.47-1.35) for clinically relevant bleeding, 0.51 (95% CI = 0.21-1.28) for major bleeding, and 0.90 (95% CI = 0.49-1.68) for clinically relevant nonmajor bleeding. The ORs for thromboembolic events and all-cause mortality were 0.66 (95% CI = 0.28-1.56) and 0.46 (95% CI = 0.15-1.40), respectively.ConclusionCurrently available evidence does not indicate a significantly increased bleeding risk of FXI/XIa inhibitors in patients with ESKD on HD compared to placebo. Their efficacy and their association with all-cause mortality need to be investigated in sufficiently powered, randomized controlled phase 3 trials.

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BackgroundAtrial fibrillation (AF) is a leading cause of stroke, necessitating effective anticoagulation. While direct oral anticoagulants (DOACs) have improved stroke prevention, bleeding risks remain a concern. Factor XI/XIa inhibitors, targeting the intrinsic coagulation pathway, offer potential for reduced bleeding, although questions remain regarding their efficacy. This systematic review evaluates the efficacy and safety of Factor XI/XIa inhibitors compared to DOACs in AF patients.MethodsWe conducted a systematic review of randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients, identified through PubMed and Embase up to January 2025. Data were synthesized narratively due to heterogeneity in study designs and outcomes.ResultsThree RCTs (AZALEA-TIMI 71, OCEANIC-AF, PACIFIC-AF) involving 16 852 patients were included. Factor XI/XIa inhibitors (abelacimab and asundexian) demonstrated significant reductions in bleeding compared to DOACs. In AZALEA-TIMI 71, abelacimab reduced major or clinically relevant non-major bleeding by 62%-69% versus rivaroxaban. In PACIFIC-AF, asundexian reduced bleeding by 50%-84% compared to apixaban. However, OCEANIC-AF showed asundexian was inferior in stroke prevention, with a 3.8-fold higher risk of stroke or systemic embolism compared to apixaban, leading to early trial termination. Abelacimab showed a trend toward higher ischemic stroke rates abelacimab (150 mg: 1.21 vs 0.59 events/100 person-years; and 90 mg: 1.24 vs 0.59 events/100 person-years), though not statistically significant.ConclusionFactor XI/XIa inhibitors significantly reduce bleeding risk in AF patients compared to DOACs, but their thrombotic efficacy remains uncertain. While promising, further research is needed to optimize their use.

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BackgroundCongenital factor XI (FXI) deficiency has a variable bleeding phenotype, and FXI activity alone does not predict perioperative bleeding. Management practices remain heterogeneous, and available evidence derives from case reports, small case series, and retrospective cohorts. This systematic review evaluated perioperative bleeding outcomes and management strategies in FXI-deficient patients undergoing surgical procedures.MethodsWe systematically searched five databases (2016-2024). Two reviewers independently screened studies, extracted data, and assessed methodological quality. Because of heterogeneity among studies, cohort data were synthesized qualitatively. Case reports were summarized descriptively, and an exploratory framework combining FXI category and fibrinolytic risk of the procedure was constructed to illustrate patterns in bleeding outcomes.ResultsTwenty-one studies met inclusion criteria: four retrospective cohorts and seventeen case reports, describing more than 590 procedures. Cohort bleeding rates ranged from 0% to 19%, with major bleeding ≤ 7%. FXI activity showed no consistent association with perioperative bleeding. Procedural factors and personal bleeding history are more often aligned with outcomes. Most case reports involved severe FXI deficiency and used FFP-based prophylaxis, often with antifibrinolytics. Bleeding events in case reports were infrequent. In the exploratory two-dimensional visualization, bleeding appeared more common among patients with FXI ≤ 10 IU/dL undergoing high-fibrinolytic procedures; however, event numbers were small and prophylaxis was widely used, limiting interpretation.ConclusionsFXI levels alone appear insufficient to predict bleeding risk in FXI-deficient patients. A multifactorial approach, integrating surgical risk and haemostatic strategy, may be required, and further study is needed to optimize preoperative management strategies for FXI-deficient patients.Clinical trial registrationClinical trial registration was not applicable for this study.

Abstract licence: CC BY-NC-ND