Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors.

Severe FXI deficiency is a rare injury-related bleeding disorder. In patients with FXI inhibitors, surgeries may be treated using recombinant activated factor VII; however, treatment safety is a major concern and the best dosing regimen as well as mode of administration is still to be defined. We describe four patients with severe factor XI deficiency and inhibitors to FXI, undergoing eight (four major) surgical procedures treated with continuous infusion of rFVIIa. Following acute MI that evolved after surgery of our first patient, all other patients were treated with low-dose bolus rFVIIa followed by low-dose continuous infusion of rFVIIa. Haemostasis was successfully achieved and no further thrombotic complications occurred. To support our clinical results ex-vivo thromboelastography studies were performed, demonstrating the differences of clot formation and lysis between patients with FXI deficiency and healthy controls and suggesting that low-dose rFVIIa corrects coagulation similarly to high-dose rFVIIa in FXI deficiency. Recombinant FVIIa at low doses may effectively induce haemostasis and seems to be a safe treatment mode in patients with FXI deficiency and inhibitors undergoing surgeries.