Acquired hemophilia, meningioma, and diphenylhydantoin therapy

A patient is reported in whom a meningioma of the lateral one-third of the sphenoid ridge was completely removed and long-term prophylaxis for seizures with diphenylhydantoin was prescribed. One and a half years later, a powerful inhibitor developed that specifically neutralized Factor VIII, the antihemophilic factor, and caused an acquired state of hemophilia. The 4-month hemorrhagic disorder was characterized initially by painless hematuria and later by intracerebral and extradural hematomas at the operative site of the previously excised meningioma. Despite the transfusion of massive quantities of concentrates of clotting factors, and the surgical evacuation of the recurrent hematomas on two occasions, the localized bleeding could not be staunched and the patient died. The types of inhibitors that cause acquired hemophilia and their modes of treatment are examined. Although it is possible that the Factor VIII inhibitor in this patient was induced by the meningioma, most previously reported tumors associated with acquired hemophilia have had an immunological basis. The most probable explanation for the acquired hemophilia in this patient was an inhibitor to Factor VIII from an autoantibody induced by the long-term use of diphenylhydantoin.