RECOMBINANT ACTIVATED FACTOR-VII (NOVOSEV EN(TM) NOVO-NORDISK) FOR HEMOSTASIS IN A PATIENT WITH AN ACQUIRED FACTOR-VIII INHIBITOR

One life threatening mediastinal hemorrhage and two limb threatening h emorrhages, one in the retroperitoneal and thigh muscles and the other in the back of the hand requiring surgical evacuation, were treated w ith recombinant activated factor VII concentrate (rFVIIa; Novoseven(TM ) Novo Nordisk) in a patient with a postpartum acquired inhibitor agai nst factor VIII. High dose activated prothrombin complex concentrate ( Feiba sTIM4 Immuno), repeatedly administered, had proven to be ineffec tive; porcine factor VIII concentrate (Hyate C Porton) had become inef fective due to a rise in inhibitor titers against human and porcine fa ctor VIII as well. 90 mu g rFVIIa per kg body weight was administered as an i.v. bolus injection every 2-3.5 hours. The treatment periods we re 22.5 days in the mediastinal and 11 days in each of the two other h emorrhages. Hemostasis was promptly achieved and maintained. All manip ulations (bone marrow biopsy, surgical evacuation of the hematoma, cha nge of venous access, withdrawal of drains, change of dressings) were done immediately after rFVIIa administration, without bleeding complic ations. There were no side effects despite the high dose, frequent and long lasting treatment with a total of 234 x 4.8 and 46 x 3.6 mg rFVI Ia. The concentrate was well tolerated, there were no signs of systemi c activation of coagulation, either in the coagulation test results or clinically, in spite of patient's factor VII levels up to 60 U/mL and prothrombin times around 6 s. No inhibitors against patient's factor VII, induced by rFVIIa, were detected. Due to its extrinsic factor VII I bypass effect, rFVIIa led to excellent hemostasis even with inhibito r titers of 376 Bethesda units against human and 44 against porcine fa ctor VIII. Nevertheless, immunosuppressive treatment with cyclophospha mide and prednisone was performed, with prompt decrease of the inhibit or titer. With factor VIII of 0.08 U/mL and an inhibitor titer of 1 Be thesda unit, the patient has been hemorrhage-free for the last seven m onths. rFVIIa has no booster effect on the factor VIII inhibitor; it s eems not to provoke systemic activation of coagulation. Therefore, it may become the treatment of choice in patients with severe hemorrhage due to acquired inhibitors.