Immune tolerance protocols using low-dose factor VIII: a review of the literature

Low-dose immune tolerance protocols use doses of factor VIII of less than 50 IU/kg/day to induce immune tolerance. Such protocols are chosen for a variety of reasons including cost, patient acceptability and ease of administration. Early published reports of low-dose protocols appeared in 1981, described small numbers of patients and moderate success. It was proposed that such protocols might modify inhibitor responses from high to low. Later reports are sparse and clinical success is again moderate. Useful treatment and expectation guidelines have emerged from experience with these protocols, and improvements for patients with inhibitors can be achieved. Consideration of immunological success, however, raises doubts about whether real immune tolerance is achieved with such protocols.