Dosing and effectiveness of recombinant activated factor VII (rFVIIA) in congenital haemophilia with inhibitors by bleed type and location: the experience of the Haemophilia and Thrombosis Research Society (HTRS) Registry (2004–2008)

Summary Control of bleeding in patients with congenital haemophilia with inhibitors requires use of bypassing agents such as recombinant activated factor VII ( rFVII a). Due to the difficulties in performing prospective clinical trials in this small subgroup of patients with haemophilia and the need for postmarketing surveillance, a large‐scale database was developed by the Hemophilia and Thrombosis Research Society. This report comprises an analysis of the database with respect to assessing dosing and efficacy of rFVII a by bleed type and location. Between January 2004 and November 2008, data from 129 inhibitor patients with 2041 rFVII a‐treated bleeds were analysed. The bleeds were primarily spontaneous (58%) and traumatic (30%). The most common locations were joints (57%), muscle (20%), mucosal (7%) and subcutaneous (6%). Median total rFVII a doses per bleeding episode for spontaneous and traumatic bleeds were 540 mcg kg −1 (4 injections/2 days) and 300 mcg kg −1 (2.5 injections/1 day) respectively. Median total rFVII a dose (mean dose, number of injections) was 480 mcg kg −1 (110 mcg kg −1 , 3) for joint; 557 mcg kg −1 (120 mcg kg −1 , 4) for muscle; 360 mcg kg −1 (120 mcg kg −1 , 3) for mucosal and 402 mcg kg −1 (117 mcg kg −1 , 3) for subcutaneous. Overall efficacy ranged from 89% to 93%; bleeding stopped in 89% of spontaneous and 93% of traumatic bleeds, 90% of joint bleeds, and 89% of muscle, mucosal,and subcutaneous bleeds. Although spontaneous bleeds require slightly higher doses than traumatic bleeds, most bleeds were treated with a median of 3–4 injections (110–130 mcg kg −1 ). Effectiveness of rFVII a was consistently high across bleeding types and locations.