Dr. David Gailani will discuss excessive bleeding in FXI-deficient patients is usually trauma-induced with a predilection for tissues in the mouth, nasopharynx, and urinary tract. This may reflect robust fibrinolytic activity in these tissues. Hemorrhage with trauma to other tissues is less frequent, and spontaneous bleeding and life-threatening intracranial and gastrointestinal bleeding are uncommon. Many FXI-deficient patients do not experience abnormal bleeding, suggesting that the deficiency does not cause a hemostatic defect in all individuals. While FXI replacement by plasma infusion was commonly used in the past to treat bleeding episodes and prepare patients for surgery, recent experience suggests that most patients can be treated with fibrinolysis inhibitors and, in some cases, low doses of recombinant factor VIIa. This approach may also be useful for treating bleeding episodes in patients on therapeutic FXIa inhibitors.  

Dr. Ophira Salomon's work with animal models and human population studies indicate that FXI promotes venous and arterial thrombosis. This, and the modest role of FXI in hemostasis, suggest that drugs neutralizing this protein could produce antithrombotic effects while causing less bleeding than currently used anticoagulants. In phase 2 testing, drugs that reduce plasma FXI or that neutralize FXIa activity were effective at preventing venous clots in patients undergoing knee replacement. In patients with cardiovascular disease, FXIa inhibition caused less clinically significant bleeding than direct oral anticoagulants and did not appear to increase bleeding when superimposed on anti-platelet therapy. Eight phase 3 trials involving nearly 80,000 patients are currently underway to establish the efficacy of FXI/FXIa inhibition compared to current standards of care in a variety of clinical situations.