Recombinant Activated Factor VII and its Role in ICU

Abstract

Recombinant activated factor VII (rFVIIa) was originally developed for the treatment of hemophilic patients with inhibitors and then used successfully for treating hemorrhages in patients with acquired hemophilia. In the last few years, along with the improvement in the knowledge of its mechanisms of action, rFVIIa has also been used with benefit as a “universal hemostatic agent” in many other nonhemophilic bleeding situations, including congenital FVII deficiencies, quantitative and qualitative platelet disorders, hepatic failure, liver transplantation, major surgery and trauma (Franchini, 2006). This review briefly analyzes the uses of rFVIIa in treatment and focuses particularly on the newer uses, for which there are only a few randomized, controlled clinical trials. Use in Hemophilic bleeding: Hemophilia A and B is treatable with highly purified plasma-derived and recombinant DNA- derived factor VIII and factor IX concentrates. However, a well recognized and potentially life-threatening complication of hemophilia is the development of neutralizing antibodies against the missing factor. Up to 25 % of patients develop an inhibitor to factor VIII, and 3-5% to factor IX. To date, therapeutic interventions in these situations have included large doses of factor VIII and activated/non-activated prothrombin complex concentrates and porcine FVIII. All these have significant drawbacks including high cost, unpredictability of response, transmission of blood-derived infections, thromboembolic complications and in the case of porcine FVIII, development of anti-porcine antibodies. All these existing therapeutic caveats led to the development of rFVIIa as a potential solution for treating hemophilia patents with inhibitors and in acquired hemophilia (Agarwal and Patnaik, 2005). The standard (and approved) intravenous (IV) dose of rFVIIa in hemophilia patients with an inhibitor is 90 μg/kg until hemostasis is achieved; for surgical patients, repeated doses are given every two hours until hemostasis is achieved and less frequently thereafter (Lawrence et al., 2004). Use of rFVIIa in Platelet Disorders: In inherited thrombocytopenia, rFVIIa was reported to enhance local fibrin deposition and to partially restore platelet aggregates in Glanzmann thrombasthenia and Bernard-Soulier syndrome (Agarwal and Patnaik, 2005).