Failure of the synthetic androgen, danazol, to increase protein S levels and prevent thrombosis in a patient with severe protein S deficiency.
A 34-year-old man with recurrent deep and superficial thromboses was found to have severe protein S deficiency. Treatment with both warfarin and adjusted-dose subcutaneous heparin failed to completely prevent thrombosis. Based on reports of increases in the endogenous anticoagulants (protein C, protein S, antithrombin III and plasminogen) with synthetic androgen therapy, the patient was treated with danazol for 8 weeks. Although the levels of antithrombin III, protein C and plasminogen increased, no change in the levels of total or free protein S or C4b binding protein was observed. Treatment was discontinued at 8 weeks when the patient developed a recurrence of superficial thrombophlebitis. The role of synthetic androgens in the treatment of patients with inherited thrombotic disorders is reviewed and potential reasons for treatment failure in this patient are discussed.
Bower
W A
WA
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Humphries
J E
JE
D000328:Adult; D000990:Antithrombin III / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects; D015935:Complement C4b / Q000187:drug effects / Q000378:metabolism; D003169:Complement Inactivator Proteins; D003613:Danazol / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins; D006801:Humans; D008297:Male; D010958:Plasminogen / Q000187:drug effects / Q000378:metabolism; D011486:Protein C / Q000187:drug effects / Q000378:metabolism; D017293:Protein S / Q000378:metabolism*; D018455:Protein S Deficiency / Q000150:complications / Q000188:drug therapy*; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000517:prevention & control*
D002352:Carrier Proteins; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011486:Protein C; D017293:Protein S; D011951:Receptors, Complement; D015935:Complement C4b; D000990:Antithrombin III; D010958:Plasminogen; D003613:Danazol