Thromb Haemost 1994; 72(02): 218-221
DOI: 10.1055/s-0038-1648842
Original Article
Schattauer GmbH Stuttgart

Changes in Haematological Indices, Blood Viscosity and Inhibitors of Coagulation during Treatment of Endometriosis with Danazol

I Ford
1   The Section of Haematology, University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, U. K.
,
C Li
2   University Department of Obstetrics and Gynaecology, Jessop Hospital for Women, Sheffield, U. K.
,
I D Cooke
2   University Department of Obstetrics and Gynaecology, Jessop Hospital for Women, Sheffield, U. K.
,
F E Preston
1   The Section of Haematology, University Department of Medicine and Pharmacology, Royal Hallamshire Hospital, U. K.
› Author Affiliations
Further Information

Publication History

Received 11 January 1994

Accepted after revision 26 April 1994

Publication Date:
24 July 2018 (online)

Summary

The effects of treatment with danazol (600 mg daily) on haemostatic and haematological function were investigated in 18 pre-menopausal women with endometriosis. Blood samples were taken at 2 pre-treatment visits, at 6, 12 and 24 weeks on treatment, and at 6 weeks after discontinuation of the drug. Haemoglobin, red cell count, haematocrit and platelet count all rose significantly during treatment with danazol (p <0.01 vs. baseline). Plasma fibrinogen levels fell significantly (p <0.01), while whole blood viscosity increased during treatment and remained significantly elevated at follow-up. The prothrombin time shortened, but remained within normal limits, and there were no significant changes in factor VII:C, Vila, or fibrinopeptide A. No significant changes were found in platelet function. Plasma B-beta 15-42 increased significantly. Functional levels of protein C, protein S, and antithrombin III, all rose significantly, above the normal range, while C4b-binding protein levels fell. We conclude that the observed changes in coagulation inhibitors and fibrinolytic activity may be considered beneficial in the context of venous thromboembolism. The rheological effects, however, indicate a degree of caution in the use of the drug in individuals considered to be at risk from arterial cardiovascular disease.

 
  • References

  • 1 Anon (leading article) (1977) Androgens in the anaemia of renal failure. Br Med J 1977; 2: 417-418
  • 2 Kluft C, Preston FE, Malia RG, Bertina RM, Wijngaards G, Greaves M, Verheijen JH, Dooijewaard G. Stanozolol induced changes in fibrinolysis and coagulation in healthy adults. Thromb Haemost 1984; 51: 157-164
  • 3 Chimbira TH, Cope E, Anderson ABM, Bolton FG. The effect of danazol on menorrhagia, coagulation mechanisms, haematological indices and body weight. Br J Obstet Gynaecol 1979; 86: 46-50
  • 4 Fraser IS, Burridge J. Danazol treatment and platelet function. Med J Australia 1980; 1: 313-314
  • 5 Ronnberg L, Ylostalo P, Jarvinen PA. Effects of danazol in the treatment of severe endometriosis. Postgrad Med J 1979; 55 (suppl.) (Suppl. 05) 21-26
  • 6 Ahn YS. Efficacy of danazol in hematologic disorders. Acta Haematol 1990; 84: 122-129
  • 7 Small M, McArdle BM, Lowe GDO, Forbes CD, Prentice CRM. The effect of intramuscular stanozolol on fibrinolysis and blood lipids. Thromb Res 1982; 28: 27-36
  • 8 Kluft C, Bertina RM, Preston FE, Malia RG, Blarney SL, Lowe GDO, Forbes CD, Protein C. an anticoagulant protein, is increased in healthy volunteers and surgical patients after treatment with stanozolol. Thromb Res 1984; 33: 297-304
  • 9 Preston FE, Malia RG, Greaves M, Kluft C, Bertina RM, Segal DS. Effect of stanozolol on antithrombin III and protein C. Lancet 1983; ii: 517-518
  • 10 Kockum C, Frebelius S. Rapid radioimmunoassay of human fibrinopeptide A - removal of cross-reacting fibrinogen with bentonite. Thromb Res 1980; 19: 589-598
  • 11 Ford I, Singh TP, Kitchen S, Makris M, Ward JD, Preston FE. Activation of coagulation in diabetes mellitus in relation to the presence of vascular complications. Diabetic Med 1991; 8: 322-329
  • 12 Greaves M, Preston FE. The laboratory investigation of acquired and congenital platelet disorders. In: Blood Coagulation and Haemostasis. A Practical Guide. 3rd edition Thomson JM. ed Churchill Livingstone; Edinburgh: 1985. pp 56-134
  • 13 Clauss A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haemat 1957; 17: 237-240
  • 14 Kitchen S, Malia RG, Greaves M, Preston FE. A method for the determination of activated factor VII using bovine and rabbit brain thromboplastins. Thromb Res 1988; 50: 191-200
  • 15 Elwood PC, Benjamin IT, Waters WE, Sweetnam PM. Mortality and anaemia in women. Lancet 1974; i: 891-894
  • 16 Lowe GDO. Blood rheology in vivo and in vitro. In: Baillière,s Clinical Haematology, vol 1 (3). Blood Rheology and Hyperviscosity Syndromes Lowe GDO. ed Bailliere Tindall; London: 1987. pp 597-636
  • 17 Lowe GDO. Laboratory investigations of pre-thrombotic states. In: Thrombosis and its Management Poller L, Thomson JM. eds Churchill Livingstone; Edinburgh: 1993. pp 1-46
  • 18 Fåhraeus L, Larsson-Cohn U, Ljungberg S, Wallentin L. Profound alterations of the lipoprotein metabolism during danazol treatment in pre-menopausal women. Fertil Steril 1984; 42: 52-57
  • 19 Claustres M, Sultan C. Androgen and erythropoiesis: Evidence for an androgen receptor in erythroblasts from human bone marrow. Hormon Res 1988; 29: 17-22
  • 20 Preston FE, Burakowski BK, Porter NR, Malia RG. The fibrinolytic response to stanozolol in normal subjects. Thromb Res J 1981; 22: 543-551
  • 21 Isacson S, Nilsson IM, Charkrabarti R. Effect of treatment with combined phenformin and ethyloestranol on the coagulation and fibrinolytic systems. Scand J Haematol 1970; 7: 404-408
  • 22 Laurell CB, Rannevik GA. Comparison of plasma protein changes induced by danazol, pregnancy and oestrogens. J Clin Endocrinol Metab 1979; 49: 719-725
  • 23 Nossel HL. Relative proteolysis of the B beta chain by thrombin and plasmin as a determinant of thrombosis. Nature 1981; 291: 165-167
  • 24 Small M, Douglas JT, Lowe GDO, Forbes CD. Increased plasmin activity during stanozolol administration. Lancet 1983; i: 1114
  • 25 Fairfax AJ, Ibbotson RM. Danazol raises antithrombin III levels in cases of familial deficiency. Lancet 1984; ii: 1272-1273
  • 26 Wautier JL, Caen JP. Treatment of antithrombin III deficiency with danazol. New EnglJ Med 1984; 311: 599
  • 27 Dahlbäck B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci USA 1981; 78: 2512-2516
  • 27 Preston FE, Briet E. Familial thrombophilia. In: Recent Advances in Haematology, vol 7 Churchill Livingstone; Edinburgh: 1993: 217-239
  • 29 Meade TW, Cooper J, Miller GJ, Howarth DJ, Stirling Y. Antithrombin III and arterial disease. Lancet 1991; 338: 850-851