Comparative thrombotic event incidence after infusion of recombinant factor VIIa versus factor VIII inhibitor bypass activity.

Thrombosis is a rare but well-recognized potential complication of Factor VIII Inhibitor Bypass Activity (FEIBA) infusion. Recombinant factor VIIa (rFVIIa) is increasingly used as an alternative to FEIBA; however, the thrombotic safety profile of rFVIIa remains incompletely characterized. To determine the incidence rates of thrombotic adverse events (AEs) after infusion of rFVIIa and FEIBA. Data from the MedWatch pharmacovigilance program of the US Food and Drug Administration, as supplemented by published case reports, were used in conjunction with estimated numbers of infusions available from manufacturers to assess comparative incidence of thrombotic AEs in patients receiving rFVIIa or FEIBA in the period from April 1999 through June 2002. Reported thrombotic AEs were rare, with incidence rates of 24.6 per 10(5) infusions (CI, 19.1-31.2 per 10(5) infusions) for rFVIIa and 8.24 per 10(5) infusions (CI, 4.71-13.4 per 10(5) infusions) for FEIBA. Thrombotic AEs were significantly more frequent in rFVIIa than FEIBA recipients (incidence rate ratio, 2.98; CI, 1.71-5.52). The most commonly documented single type of thrombotic AE after rFVIIa infusion was cerebrovascular thrombosis, while myocardial infarction was the most frequent type in patients receiving FEIBA. Contrasting AE reporting patterns between rFVIIa and FEIBA may have contributed to the observed difference in thrombotic event incidence. Nevertheless, this comprehensive pharmacovigilance assessment does not support superior thrombotic safety of rFVIIa and suggests that thrombotic AE risk may be higher in rFVIIa than FEIBA recipients.