Efficacy of Prothrombin-Complex Concentrates in Hemophiliacs with Antibodies to Factor VIII

Abstract

The therapeutic efficacy of prothrombin-complex concentrates in patients with hemophilia and inhibitors (antibodies) to factor VIII has been increasingly debated. We therefore entered 51 hemophiliacs with factor VIII inhibitors into a double-blind randomized crossover study to compare two commercial prothrombin-complex concentrates (Konyne and Proplex) and an albumin placebo. Acute hemarthrosis of the elbow, knee, or ankle was treated with a single dose of a test preparation and assessed six hours later with objective and subjective criteria. In all measurements the concentrates were significantly more effective than the placebo. The data indicate that although prothrombin-complex concentrates, when used in a single dose, are only partially effective in the treatment of joint hemorrhage in hemophiliacs with inhibitors, their continued use for acute hemarthrosis is justified in the absence of any other effective and readily available therapy for this disorder.

Use of human factor VIIa in the treatment of two hemophilia A patients with high-titer inhibitors.

“…Recently, the use concentrates of the unactivated and activated prothrombin-complex have met with limited success in some cases (1)(2)(3)(4)(5), while in others, evidence of disseminated intravascular coagulation or thromboembolic complications were observed (6)(7)(8). The putative hemostatic agent(s) in these preparations has never been identified, although Factor VIIa has been suggested as one possibility (9).…”

Effect of recombinant factor VIIa on the hemostatic defect in dogs with hemophilia A, hemophilia B, and von Willebrand disease.

“…Such concentrates had a hemostatic effect, but thrombosis was observed with higher dosage (10,11). The purification of factor VII from plasma (12) allowed preliminary testing of isolated human factor VIa in microgram amounts in inhibitor hemophilia.…”

Comprehensive management of haemophilia A and B

“…Increased efficacy of APCC as compared with PCC has not been well documented by controlled clinical trials. Used in the treatment of inhibitor bleeding since the 1970s, PCC and APCC are effective but less so than specific factor therapy 39 . Although this therapy is short acting, its frequent use has significant drawbacks.…”