FIXing factor VIII inhibitors.

摘要

Inhibitors of FVIII are antibodies that block its coagulation function. For congenital hemophilia A, inhibitors develop in approx 20% of all patients, for an overall incidence of 1:50 000 of the general population, or approx 6000 people in the United States. Acquired FVIII inhibitors can develop spontaneously in patients with a normal FVIII gene, and occur in approx 1 per 1 million people. Bleeding episodes in such patients are often treated with so-called bypass agents, which allow coagulation to occur in the absence of FVIII activity. One bypass agent is recombinant FVIIa, which activates FX of the common pathway of coagulation, and FIX of the extrinsic pathway. A second bypass agent is Factor 8 Inhibitor Bypassing Activity (FEIBA), a prothrombin complex concentrate that contains activated vitamin K- dependent coagulation factors. FVIIa and FEIBA appear to be roughly equivalent in their efficacy for minor bleeding episodes. FVIIa is given up to every 2 hours at a cost of approxdollar8000 per dose for an adult, while FEIBA is given up to every 8 hours at a cost of approx dollar8500 per dose. One of the major drawbacks for both of these treatments is the short half-life of the active proteins), and the cost of treatment for a single major bleed or surgery can easily exceed dollar250 000. The development of a hemostatic agent that is active in the presence of an inhibitor but has a longer half-life could reduce the cost of treating bleeding episodes.