Safety of factor VIII inhibitor bypass activity (FEIBA^®): 10‐year compilation of thrombotic adverse events

Abstract

Published and unpublished spontaneously reported thrombotic adverse events (AEs) in factor VIII inhibitor bypass activity (FEIBA(R)) recipients were compiled for the most recent 10-year period during which FEIBA(R) units equivalent to 3.95 x 105 typical infusions were distributed worldwide. A total of 16 thrombotic AEs were documented over the 10-year period, corresponding to an incidence of 4.05 per 105 infusions (95% CI, 2.32-6.58 per 105 infusions). Disseminated intravascular coagulation (n=7) and myocardial infarction (n=5) were the most frequent thrombotic AEs. One fatality occurred in an 87-year-old metastatic cancer patient. In 13/16 (81%) patients known risk factors were present, most commonly FEIBA(R) overdose in 8/16 (50%), obesity in 3/16 (19%) and serum lipid abnormalities in 2/16 (12%). These findings indicate that thrombotic AEs in FEIBA(R) recipients are very rare. Recognition of risk factors and avoidance of FEIBA(R) overdosage may avert thrombotic AEs.

Prevention of bleeds in hemophilia patients with inhibitors: Emerging data and clinical direction

“…Activated PCC products have the potential for abnormal thrombus formation resulting in myocardial infarction and disseminated intravascular coagulation when used in large or repeated doses in excess of the recommended doses [26,27]. Because aPCCs are virally inactivated products derived from human plasma, they also carry the very slight, but potential, risk of viral transmission [28].…”

An observational, prospective, two-cohort comparison of a fixed versus variable dosing strategy of prothrombin complex concentrate to counteract vitamin K antagonists in 240 bleeding emergencies

“…[5][6][7] Furthermore, lingering perceptions regarding the thrombotic risk associated with PCC products in hemophiliacs, in addition to limited licensing of PCC products for VKA reversal, have stopped clinicians in many countries from using PCC for this purpose. [8][9][10] Although PCC treatment for VKA reversal in bleeding patients is different from PCC treatment in hemophiliacs with respect to dosing frequency, the lowest possible dose should still be considered.…”

Successful self‐infusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor

“…Concern remains, however, regarding the potential for thrombosis following long-term prophylaxis with APCCs. Pharmacovigilance reports for worldwide FEIBA use during the 10-year period 1990-1999 showed an overall adverse event rate of 55 events per 100,000 infusions [14]. Of these, 17 events in 16 patients were thrombotic, with an incidence of 4.05 thrombotic events per 100,000 infusions; the most frequently reported events were DIC (7/16 patients) and myocardial infarction (5/16 patients; one fatal).…”