Prospective evaluation of systemic coagulation function during anti-amyloid monoclonal antibody therapy in...

Anti-amyloid monoclonal antibodies such as lecanemab are increasingly used to treat Alzheimer's disease (AD) and are associated with amyloid-related imaging abnormalities (ARIA), including hemorrhagic findings (ARIA-H). Whether anti-amyloid therapy is associated with systemic alterations in coagulation function is unknown. We sought to evaluate systemic coagulation function in patients receiving lecanemab compared with untreated AD controls. We prospectively collected blood samples from 20 lecanemab-treated participants with AD at baseline and after 8-10 weeks of therapy, and from 48 untreated AD controls. We assessed thrombin generation in platelet-poor plasma initiated with tissue factor and measured lag time, time to peak, peak thrombin, velocity, and area under the curve. We also evaluated fibrin formation by turbidity assays, yielding maximum rate of clot formation and time to Vmax. Comparisons were performed between groups and within treated participants over time. Mean age was 72.8 years (SD 8.1); 51.5% were female. No significant differences were observed in thrombin generation or fibrin formation between treated and untreated participants, or from baseline to follow-up among treated participants. Two lecanemab-treated participants developed ARIA-H. Anti-amyloid monoclonal antibody therapy was not associated with detectable alterations in plasma coagulation parameters in this cohort. These findings do not support measurable systemic coagulation perturbations detectable in plasma but do not rule out localized cerebrovascular, endothelial, platelet-mediated, or other microvascular mechanisms underlying ARIA-H, which warrant future investigation.