Relationship between factor VII activity and clinical efficacy of recombinant factor VIIa given by continuous infusion to patients with factor VIII inhibitors

A multicenter prospective study of recombinant activated factor VII (rFVIIa ,) given by continuous infusion (CF) to treat severe hemorrhages and to han dle surgical procedures was carried out. Relations between clinical efficac y, dosages used and levels of FVII coagulant activity (FVII:C) achieved in plasma were also evaluated. Case material included 25 patients with hemophi lia (9 children and 16 adults) with hiah-resporiding inhi itors and 3 patie nts with acquired factor VIII inhibitors. Overall, 35 Cl courses were given for 10 spontaneous bleeding episodes, I I major surgical procedures and 14 minor surgical procedures. Bolus doses of 90 to 150 mug/kg (median: 100) W ere followed by Cl given at median rates of 20 mug/kg/h for major surgery a nd of 17 and 16 mug/kg/h for minor surgery and spontaneous hemorrhages. Sat isfactory hemostasis was obtained in 30 of 35 courses (88%). rFVIIa Cl was ineffective in 2 hemophiliacs undergoing surgical operations and in another hemophiliac with hemoperitoneum who had to be switched to other treatments (high doses of porcine or human factor VIII concentrates). rFVIIa Cl was p artially effective in 2 hemophiliacs who had mild local bleeding after mino r surgery. The Cl rates and the corresponding FVII:C levels in plasma were similar in effective, partially effective and ineffective courses (median r ate: 17, 20 and 20 mug/kg/g, respectively; median FVII:C: 14, 18 and 18 IU/ ml, respectively). A single adverse event was observed, superficial thrombo phlebitis. This study confirms that rFVIIa given by Cl is effective in a hi gh proportion of patients with factor VIII inhibitors. It also demonstrates that FVII:C levels attained in plasma do not always predict efficacy becau se similarly levels were attained during successful treatments. L in those that failed.