Manifestations of Factor VIII Inhibitor in the Head and Neck

Abstract

Hemophilia A is the most severe of the inherited bleeding disorders. Otolaryngologists are frequently asked to assist in the care of a patient with this disorder who has intractable bleeding from sites in the head and neck. This disorder is transmitted in an X-linked recessive manner and results from factor VIII deficiency. Factor replacement therapy has contributed much to the management of acute bleeding episodes and the prevention of long-term sequelae in patients with hemophilia. A consequence of factor replacement therapy that occurs in as much as 16% of patients is the development of antibodies to the exogenous factor. These antibodies inactivate any supplemental factor VIII, resulting in continued bleeding despite attempts at replacement therapy. This poses an extremely challenging clinical problem because other standard therapies have had limited usefulness. Activated prothrombin complex has been shown to be efficacious in the treatment of patients with inhibitors. This has led to the production of factor VIII inhibitor bypassing activity (FEIBA), which contains activated forms of factors II, VII, IX, and X. The mechanism of action of this preparation remains unknown, but it seems to bypass the need for factor VIII in the clotting cascade. Factor VIII inhibitor bypassing activity is not as effective as factor VIII concentrates in patients with normally responsive hemophilia, and patients with low inhibitor levels may be given larger doses of factor VIII. Disseminated intravascular coagulation is most often mentioned as a potential complication of the administration of factor VIII inhibitor bypassing activity, although it has been rarely reported. Otolaryngologists should be familiar with this clinical phenomenon and understand its implications. Two patients with bleeding diatheses were recently treated at our institution.

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

“…Fifty‐five AEs of all types were spontaneously reported among patients receiving FEIBA ® during the compilation period. A total of 16 thrombotic AEs, accounting for 29% of all 55 AEs, were documented during 1990–99: seven DIC [7, 9–11]; five MI [12–16]; two suspected pulmonary embolisms [11]; and two thromboses [11,16]. Data related to the thrombotic AEs are summarized in Table 1.…”

“…In two congenital haemophilia patients the type of haemophilia was unspecified. Eleven of the reported AEs were published [7, 9–16].…”

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

“…Two published case reports were excluded because the patients had received both rFVIIa and FEIBA [38,39]. A thrombotic AE after FEIBA infusion described in a 1999 publication was not included, since the event occurred in 1997 [40]. The 2000 report of two patients developing thrombotic AE after rFVIIa was not included because the patients were treated prior to 1999 [41].…”

Blindness following soft tissue trauma in a child with haemophilia A

“…Haemophilia A is the most severe of inherited bleeding disorders, as it results from factor VIII deficiency and is transmitted in an X‐linked recessive manner 6 . However, a significant number of cases (approximately 30%) also arise as a result of spontaneous mutation 7 .…”

“…However, a significant number of cases (approximately 30%) also arise as a result of spontaneous mutation 7 . Factor replacement therapy has contributed much to the management of acute bleeding episodes and the prevention of long‐term sequelae 6 . The modern approach consists of the intravenous administration of a concentrate factor in a prophylactic form, two or three times a week to prevent spontaneous bleeding 8 .…”