Mechanistic Rationale for Factor XIa Inhibition

In this first episode of the NeurologyLive® Special Report, Mike Sharma, MD, Stroke Neurologist and Michael G. DeGroote Chair in Stroke Prevention at McMaster University, discusses the biological underpinnings and therapeutic rationale behind targeting factor XIa for stroke prevention. Drawing from early observations of individuals with congenital factor XI deficiency—who experienced minimal bleeding yet reduced stroke and venous thromboembolism risk—he explains how this insight evolved into a novel antithrombotic strategy.

Dr. Sharma describes how factor XIa inhibitors like asundexian work by interfering with thrombus formation within vessels, while leaving normal hemostasis intact. This separation between thrombosis and bleeding control represents a potential breakthrough for neurologists seeking safer long-term antithrombotic options. Early preclinical and human data, he notes, suggest that inhibiting factor XIa may lower recurrent stroke risk without prolonging bleeding time, paving the way for next-generation agents with a markedly improved safety profile.