Effect of danazol on coagulation parameters and bleeding in hemophilia

H. S. Garewal, J. J. Corrigan Jr, B. G. Durie, M. A. Jeter and M. L. Damiano

Danazol was given orally at a dose of 600 mg/day to six hemophiliacs for eight to 14 weeks. All patients showed a significant decrease in activated partial thromboplastin time (APTT) beginning with the first measurement (two weeks) and persisting until use of the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated. Despite the shortened APTT, bleeding episodes continued in the severe hemophiliacs and the patient with Christmas disease. In four patients, bleeding appeared to increase in severity or change in pattern, and in two cases the bleeding manifestations did not respond to usual factor infusions but responded to discontinuation of the drug therapy and further factor replacement. Euglobulin lysis times were measured in five patients (one hemophiliac and four with nonhemophilic conditions) who were receiving danazol. The lysis times were markedly shortened. Increased fibrinolytic activity may be responsible for the increased bleeding manifestations in danazol-treated hemophiliacs.