An overview of the history, clinical practice concerns, comparative studies and strategies to optimize therapy of bypassing agents.

Despite significant advances in the treatment of haemophilia, including availability of recombinant coagulation factor replacement products and the use of prophylactic infusion regimens, the segment of haemophilic patients who develop inhibitory antibodies remain at higher risk for morbidity and mortality associated with recurrent or uncontrolled bleeding events. Bypassing agents represent the mainstay of treatment and prevention of bleeding. The most commonly used of the currently available therapeutic agents are a plasma-based therapy, factor eight inhibitor bypassing activity, vapour heated, and a recombinant therapy, NovoSeven (recombinant activated factor VIIa). A substantial body of literature exists to document efficacy and adverse event profiles for these two products. There is, however, a paucity of data arising from adequately powered prospective trials to determine optimal treatment and dosing in various clinical situations. Certain clinical circumstances, patient profiles, individual responses, or provider predilection may lead to preferential use of one of these products over the other; however, the continued presence of both agents in the therapeutic armamentarium remains critically important to this fragile population. The historical use, clinical practice concerns, published comparative studies and methods for optimization of these two bypassing agents are reviewed.