The management of factor VIII inhibitors in non-hemophilic patients

The experience of 118 coagulation specialists in the treatment of 215 non-hemophilic patients with inhibitors to factor VIII:C was recently reviewed. In approximately half these patients there were no illnesses which may have predisposed to inhibitor formation, while "auto-immune" disorders such as rheumatoid arthritis and systemic lupus erythematosus were present in 18%. Major bleeding was reported in 87% of the patients, and 22% died as a consequence of having the inhibitor. While inhibitors in a few patients, particularly those that developed in association with pregnancy, disappeared without treatment, most patients were given prednisone in doses of up to 2 mg/kg per day. This therapy was most effective in patients without associated disorders, but disappearance of the inhibitor in patients with rheumatoid arthritis usually occurred only when cyclophosphamide or azathioprine was added to the therapeutic regimen. Subjects with inhibitor titers in excess of 10 Bethesda Units were usually refractory to all therapeutic modalities. The management of acute bleeding episodes in the patient with an inhibitor has been the subject of a number of recent reports. Successful stratagems have included intensive plasmapheresis combined with massive infusion of antihemophilic factor concentrates, the use of porcine factor VIII concentrates, and the administration of clotting factor concentrates which bypass the locus of factor VIII participation in clotting. All of these methods expose the patient to potential serious side-effects, and the ultimate solution to the problem of the development of factor VIII inhibitors will require insights into the reasons for the production of these antibodies and measures to regulate aberrant immune processes.