Treatment of acquired haemophilia with recombinant activated FVII: a critical appraisal

Abstract

Acquired haemophilia is a rare bleeding disorder usually caused by the spontaneous formation of inhibitory antibodies to coagulation FVIII. The disease occurs most commonly in the elderly, and although acquired haemophilia may be associated with a variety of underlying conditions, up to 50% of reported cases are idiopathic. Treatment options have traditionally involved human FVIII or FIX replacement therapy (if the inhibitor titre allows), porcine FVIII or the use of activated pro-thrombin complex concentrates. Recombinant activated coagulation FVII (rFVIIa) was available on an emergency and compassionate use basis from 1988 to 1999 at sites in Europe and North America. It has been registered in Europe for use in treating acquired haemophilia since 1996 and has recently been licensed for this indication in the United States. By directly activating FX on the surface of activated platelets at the site of injury (thereby bypassing FVIII and FIX), rFVIIa can circumvent the actions of inhibitory antibodies present in acquired haemophilia patients. This paper provides an overview of experiences with rFVIIa for the treatment of acquired haemophilia from the NovoSeven compassionate and emergency use programmes (1989-1999), the Hemophilia and Thrombosis Research Society Registry, and independent published reports from January 1999 to September 2005. rFVIIa has been reported to provide safe and effective haemostasis as a first line therapy in patients of all ages for a variety of surgical and non-surgical bleeding situations.

International recommendations on the diagnosis and treatment of patients with acquired hemophilia A

“…Overall, the response to treatment was rated effective or partially effective in 90% (111/124) of nonsurgical bleeding [102/115 (89%) spontaneous; 9/9 (100%) traumatic] and 86% (49/57) of surgical cases. 31 Two earlier studies reported rFVIIa efficacy as first-line or as salvage therapy. An effective response was observed in 100% of the episodes in which rFVIIa was used as firstline therapy; effective or a partial response was observed in 75% and 17% of the episodes when used as salvage therapy respectively.…”

A case of acquired hemophilia A in an elderly female

“…rFVIIa works by initiating formation of complex between tissue factor and FVIIa, leading to increased thrombin production and accelerated fibrin clot formation at sites of vascular injury bypassing the intrinsic pathway. rFVIIa has been noted to be effective/partially effective in 90% nonsurgical and 86% surgical cases [12]. Some studies have reported it to have an effective response in 100% cases when used as first line therapy, 75% good or partial response as second line therapy, and 17% response when used as salvage therapy [10,13].…”

Acquired Hemophilia A: A Case Report

“…13 In patients with high titer inhibitors (>5 BU), bypassing agents, such as FEIBA and rVIIa, are the mainstay of therapy for acute hemorrhage. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] The recommended dose of FEIBA, ranges between 50-100 U/kg administered every 6-12 hours, not to exceed a single dose of 100 U/kg or a daily dose of 200 U/kg. 3,14,15,16 In one study, FEIBA controlled hemorrhage in 86% of patients.…”

“…14 The recommended dose of rVIIa ranges from 90 to 120 mcg/kg every 2-3 hours. [17][18][19][20][21] A pooled analysis of data of 139 patients from different sources reported an efficacy rate of 88%. 17 Venous thromboembolic disease (VTE) is an adverse event associated with both of these agents.…”