Effect of danazol on clotting factor levels, bleeding incidence, factor
infusion requirements, and immune parameters in hemophilia
P Saidi, BZ Lega, HC Kim and K Raska
Several recent studies have reported conflicting results on the
effectiveness of danazol, an attenuated androgen, in raising plasma levels
of clotting factors VIII and IX in patients with hemophilia. We undertook a
randomized, double-blind cross-over trial using 8 weeks' administration of
danazol (D), 600 mg/d, and 8 weeks' administration of placebo (P) separated
by 2 weeks of rest in 12 patients with hemophilia A and four patients with
hemophilia B. Plasma factor VIII and IX levels, frequency and type of
bleeding episodes, amount of factor concentrate infused, fibrinogen,
fibrinolysis assays, antithrombin III, liver function, and immune
parameters were followed. During the danazol phase a minimal increase was
noted in the average clotting factor levels, an increase that, although
statistically significant, was of hemostatically marginal magnitude.
Significant increases in protein C and plasminogen levels, however, were
observed during the danazol period, suggestive of danazol-mediated enhanced
fibrinolysis. Clinically, bleeding frequency was significantly increased,
and more clotting factor was consumed during the danazol period.
Furthermore, eight episodes of hematuria and oral mucosal bleeding was
reported during the danazol phase in contrast to only one episode of
hematuria during the placebo phase, consistent with an enhancement of
fibrinolytic activity with danazol. We conclude that danazol does not have
a hemostatically significant effect on plasma levels of factor VIII and IX
but may be associated with enhancement of fibrinolytic activity, resulting
in increased bleeding frequency and requiring more clotting factor
infusions. Therefore, danazol is not a viable alternative in the treatment
of hemophilia.
Volume 68,
Issue 3,
pp. 673-679,
09/01/1986
Copyright © 1986 by The American Society of Hematology
