Efficacy of danazol in a patient with congenital protein-S deficiency: paradoxical evidence for decreased platelet activation with increased thrombin generation.
Danazol, a synthetic attenuated anabolic steroid, has been administered for 36 months to a 32 year old male with hereditary Protein S (PS) deficiency who had become non-compliant for warfarin therapy. The patient has an eleven year history of venous thrombosis. Since danazol therapy was initiated, the patient has not experienced a thrombotic event or adverse side-effects. Levels of PS, other inhibitors, fibrinolytic components, and markers for thrombin and platelet activation were measured prior and subsequent to therapy. Following danazol administration, marked and sustained increases were noted in Free Protein S, Antithrombin, and Protein C. Platelet CD62 (P-selectin) positivity which was elevated before therapy, decreased to assay threshold limits within five weeks. Both Prothrombin Fragment 1.2 and thrombin-antithrombin complexes were elevated post danazol therapy indicating continued clearance of generated thrombin. These data suggest that the protective effect provided by danazol in this patient with hereditary PS deficiency, may in large part be due to suppression of platelet activation by thrombin inhibition than simply through elevation of PS.
Ledford
M R
MR
Department of Pathology, University of Miami School of Medicine, FL 33101, USA. mledford@mednet.med.miami.edu
Horton
A
A
Wang
G
G
Brito
M
M
Delgado
L
L
D000328:Adult; D000925:Anticoagulants; D002469:Cell Separation; D003613:Danazol / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005342:Fibrinolysis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D018455:Protein S Deficiency / Q000097:blood / Q000151:congenital / Q000188:drug therapy*; D013917:Thrombin / Q000096:biosynthesis*; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D004965:Estrogen Antagonists; D019007:P-Selectin; D014859:Warfarin; D013917:Thrombin; D003613:Danazol