Treatment of a High Titer Anti - Factor - Vill Antibody by Continuous Factor VIII Administration : Report of a Case

I NHIBITORS to factor VIII develop in approximately 1 5% of patients with hemophilia with an incidence of approximately 8 per 1,000 patient-years of observation.’ Clinically, these can be divided into high response inhibitors, which exhibit an anamnestic response after exposure to factor VIII, and low response inhibitors, which do not exhibit significant anamnesis.2 Because of their neutralizing activity, high response inhibitors severely compromise the effectiveness of factor VIII replacement for bleeding episodes. The recent development of control-activated factor lx concentrates3 and safer animal factor VIII concentrates6 has provided new approaches to the treatment of bleeding in hemophiliac patients with high responding inhibitors to factor VIII. While these and other modalities7 have been of unquestioned benefit to some patients, they may not be uniformly efficacious, and they do not solve the basic problem-the inhibitor itself. Treatment methods aimed at eradicating the inhibitor, like immunosuppressive therapy, have been described in the past, but are effective in only a small number of patients.8 Recently, Brackmann and coworkers from the Bonn Hemophilia Center have reported the use of long-term high-dose factor VIII replacement together with concurrent administration ofactivated factor IX concentrate in a large number of patients with both high and low responding factor VIII inhibitors.9’0 Of I 7 patients with high responding inhibitors, I 5 have completed therapy and all but one of these patients has had complete disappearance of their inhibitor as judged by postinfusion fall-off and recovery of factor VIII. Eradication of the inhibitor occurred within an average of 25 mo from the initiation of treatment. Subsequently, other investigators have reported similar treatment methods with variable success.” ‘ Although many patients treated by the Bonn protocol remain on prophylaxis with factor VIII, at least three patients have been off maintenance factor VIII for periods of time up to 5 yr without reappearance of the inhibitor.’0”2 We report an additional patient treated with a continuous high-dose factor VIII replacement regimen, modified after that of Brackmann and Egli.’#{176} elbow and bilateral knee replacements under conventional factor VIII coverage. Studies performed during the course of treatment indicated that the reduction in the inhibitor was the result of specific tolerance to factor VIII.