Recombinant Activated Factor VII as a Temporary Reversal Agent for Warfarin Anticoagulation: A Cautionary Report on an Off-Label Application

Abstract not available. Introduction provided instead.

Therapy with warfarin, a vitamin K antagonist, poses increased risks for bleeding during major orthopedic surgical procedures. Normalization of the prothrombin time after cessation of warfarin treatment is often delayed by several days.¹ Pharmacologic reversal with vitamin K or infusion of plasma products may be indicated in specific clinical situations. Although these treatments are effective, there are wide variations in doses, volumes, and rates of reversal, as well as potential complications such as anaphylaxis, fluid overload, transmission of infective agents, and thromboembolism.^2-4

Recombinant activated factor VII (rFVIIa) is a genetically engineered coagulation protein that was approved by the US Food and Drug Administration (FDA) in 1999 for the treatment of bleeding in patients with hemophilia and antibodies against coagulation factor replacements. This medication was subsequently licensed for 2 additional indications: (1) bleeding prophylaxis for surgical procedures in patients with hemophilia and factor inhibitors and (2) control of bleeding in patients with congenital factor VII deficiency. Off-label administration rFVIIa has been reported as a potential novel means of rapidly and temporarily reversing the anticoagulation
effects of warfarin.^3,5-8

In this case report, we describe a patient on chronic warfarin therapy, considered at high risk for pulmonary emboli with cessation of warfarin anticoagulation, who
was given rFVIIa to address the potential for excess bleeding during rotator cuff repair surgery. We also review other reported off-label applications of rFVIIa, the risks for thrombosis, and the need for further study.