Benefits of Danazol Treatment in Patients With Hemophilia A (Classic Hemophilia)

Gralnick, Harvey R.

doi:10.1001/jama.1985.03350320075020

Cited by 11 publications

(10 citation statements)

References 6 publications

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“…This effect, however, appears more general and not specific for the factor IX Leyden gene because similar effects were also seen for other proteins, such as factor VIII (25)(26)(27). Our results obtained from the in vitro assay system agree well with this observation.…”

Section: Methodssupporting

confidence: 87%

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

Hirosawa

Fahner

Salier

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Hemophilia B Leyden is characterized by unusual developmental regulation of factor IX synthesis in affected individuals. One family affected with the hemophilia B Leyden phenotype was found to have a specific single-base mutation (G----A) at nucleotide -6 of the factor IX gene. The mutation site was found in a small region of the 5'-untranslated sequence designated the Leyden-specific region (LS region). This region, approximately 40 base pairs in length, contains the unique mutation sites of all the known factor IX Leyden genes (five families) analyzed to date. This fact strongly suggests that the LS region is directly or indirectly involved in the developmental regulation of factor IX biosynthesis. Base changes at nucleotide -20 as well as at nucleotide -6 and deletions of the 3' half of the LS region reduced expression activity of the factor IX gene to approximately 15-31% that of the normal control, as assessed in a cultured cell (HepG2) expression system. The LS region binds at least two proteins. Androgen significantly increased the transcriptional activities of both mutant and normal factor IX genes in a concentration-dependent manner.

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Section: Methodssupporting

confidence: 87%

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

Hirosawa

Fahner

Salier

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…These results were initially confirmed by the same authors in 11 patients with hemophilia A [16]; how ever, others observed either minimal in creases in factor levels, no decrease in bleed ing tendency or an excess of adverse effects [5,17], In the only randomized placebo-con trolled trial of danazol in hemophilia A. Metha et al [18] observed that only some pa tients with hemophilia A obtained a signifi cant increase in factor VIII levels, but that responders appeared to benefit clinically from this increased factor level. No adverse effects were seen during 3 months of treatment with 300 mg/day of danazol in this study [ 18], In 1980, Fiessinger and Aiach [ 19] gave an 8-month course of stanozolol to a patient with hereditary antithrombin III deficiency.…”

Section: Discussionsupporting

confidence: 59%

Failure of the Synthetic Androgen, Danazol, to Increase Protein S Levels and Prevent Thrombosis in a Patient with Severe Protein S Deficiency

Bower

Humphries²

1995

Pathophysiol Haemos Thromb

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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.

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“…It is possible that the response seen in our case was because of the longer duration of therapy and/or a higher baseline FX level in contrast to that reported by Sumer et al It is also possible that the response to danazol may be characteristic of particular genetic variants of factor-de®cient patients [11]. Gralnick et al have postulated that the varying response to danazol re¯ects the heterogeneity of the basic pathogenesis of haemophilia [7]. Some patients may have functional genes that can be activated by androgens such as danazol whereas others may have abnormal genes or abnormal regulatory mechanisms that cannot be activated.…”

Section: Discussioncontrasting

confidence: 52%

Danazol therapy in factor X deficiency

et al. 2001

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Factor X (FX) deficiency is a rare coagulation disorder that usually presents with bleeding manifestations and is treated with fresh frozen plasma or prothrombin complex concentrates. We report a case of FX deficiency in which the patient presented with bleeding as well as thrombosis. The patient responded to Danazol and relapsed when the drug was stopped. The occurrence of thrombosis in FX deficiency and the role of Danazol in coagulopathies are reviewed.

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Benefits of Danazol Treatment in Patients With Hemophilia A (Classic Hemophilia)

Cited by 11 publications

References 6 publications

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

Failure of the Synthetic Androgen, Danazol, to Increase Protein S Levels and Prevent Thrombosis in a Patient with Severe Protein S Deficiency

Danazol therapy in factor X deficiency

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