Effect of Stanozolol on Factors VIII and IX and Serum Aminotransferases in Haemophilia

Summary

The treatment of haemophilia has been dramatically improved since the introduction of factor VIII and IX concentrates, however these concentrates have brought new problems such as hepatitis and A.I.D.S. An oral agent which could raise endogenous levels of factor VIII and IX would be of great benefit. Danazol, an anabolic steroid, has recently been shown to increase levels of factors VIII and IX in haemophilia. We therefore studied the effect of stanozolol, a closely related anabolic steroid, in 15 patients with haemophilia A or Christmas disease over a 2-4 week period. There was no consistent change in factor VIIIc or factor IX, and fibrinolysis was significantly enhanced. No effect was apparent on the incidence of spontaneous bleeds. However serum aminotransferases which were abnormal in 11 of the 15 patients at the start of the study fell significantly with stanozolol therapy. This raises the interesting possibility that anabolic steroids may be beneficial in patients with chronic liver diseases.

Keywords

Stanozolol - Haemophilia - Fibrinolysis - Serum aminotransferases

• References

• 1 Forbes CD. Clinical aspects of haemophilias and their treatment. In Disorders of Haemostasis. Ratnoff OD, Forbes CD. (eds.) Grune and Stratton; New York: 1984. pp 177-239
• 2 Enck RE, Betts RF, Brown MR, Miller G. Viral serology (hepatitis B virus, cytomegalovirus, Epstein-Barr virus) and abnormal liver function tests in transfused patients with hereditary haemorrhagic diseases. Transfusion 1979; 19: 32-38
• 3 Mirick GS, Ward R, McCollum RW. Modification of post transfusion hepatitis by gamma globulin. N Eng J Med 1965; 273: 59-65
• 4 Knodell RG, Conrad ME, Ishak KG. Development of chronic liver disease after acute non-A non-B post transfusion hepatitis. Gastroenterology 1977; 72: 902-909
• 5 Menitove JE, Aster RH, Casper JT, Lauer SJ, Gottscholl JL, Williams JE, Gill JC, Wheeler DV, Piaskowski BS, Kirchner P, Montgomery RR. T-lymphocyte subpopulations in patients with classic hemophilia treated with cryoprecipitate and lyophilized concentrates. N Eng J Med 1983; 308: 83-86
• 6 Pneumocystis Carinii pneumonia among persons with hemophilia A. Morbid Mortal Weekly Rep 1982; 31: 365-377
• 7 Andrews MC, Wentz AC. The effects of danazol on gonadotrophins and steroid blood levels in normal and anovulatory women. Am J Obstet Gynec 1975; 121: 817-828
• 8 Noble AD, Letchworth AT. Treatment of endometriosis: A study of medical management. Br J Obstet Gynaec 1980; 87: 726-728
• 9 Mansel RE, Wisbey JR. The effect of gonadotrophin suppression by danazol on symptomatic benign breast disease. Brit J Surg 1980; 67: 827
• 10 Chimbira TH. Reduction of menstrual blood loss by danazol in unexplained menorrhagia. Lack of effect of a placebo Br J Obstet Gynaec 1980; 87: 1152-1158
• 11 Gralnick HR, Rick ME. Danazol increases factor VIII and factor IX in classic hemophilia and Christmas Disease. N Eng J Med 1983; 308: 1393-1395
• 12 Small M, McArdle BM, Lowe GD O, Forbes CD, Prentice CR M. The effect of intramuscular stanozolol on fibrinolysis and blood lipids. Thromb Res 1982; 28: 27-36
• 13 Preston FE, Burakowski BK, Porters NR, Malia RG. The fibrinolytic response to stanozolol in normal subjects. Thromb Res 1981; 22: 543-551
• 14 Davidson JF, Lochhead M, McDonald GA, McNicol GP. Fibrinolytic enhancement by stanozolol. Br J Haematol 1972; 222: 543-559
• 15 Jarrett PE M, Morland M, Browse NL. Treatment of Raynaud’s phenomenon by fibrinolytic enhancement. Br Med J 1978; 2: 523-525
• 16 Burnaud K, Clemenson G, Morland M, Jarrett PE M, Browse NL. Venous lipodermatosclerosis: treatment by fibrinolytic enhancement and elastic stockings. Br Med J 1980; 280: 7-12
• 17 Cuncliffe WJ, Dodman B, Roberts BE, Tebbs EM. Clinical and laboratory double-blind investigation of fibrinolytic therapy in cutaneous vasculitis. In Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (Eds.) New York: Raven Press; 1975. i 325-332
• 18 Gribbin HR, Flavell MattsS. Mode of action and use of anabolic steroids. Br J Clin Prac 1976; 30: 3-9
• 19 Ludlum CA, Peake IR, Allen N, Davies BL, Furlong RA, Bloom AL. Factor VIII and fibrinolytic response to deamino-8-D-arginine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrands disease. Br J Haematol 1980; 45: 499-511 a
• 20 Breckenridge RT, Ratnoff OD. Studies on the nature of the circulatory anticoagulant directed against the antihaemophilic factor. Blood 1962; 20: 137-149
• 21 Laurell CB. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibody. Anal Biochem 1966; 15: 45-49
• 22 Giddings JC. Hereditary coagulation disorders: laboratory techniques in blood coagulation and haemostasis. Thomson JM. (Ed.) Churchill Livingstone; London: 1980. pp 117-157
• 23 Kluft C, Brakman P, Veldhuyzen-Stalk EC. Screening of fibrinolytic activity in plasma euglobulin fractions on the fibrin plate. In Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Samama MM, Desnoyers PC. (eds.) Raven Press; New York: 1976. 2 57-65
• 24 Born GV R. Aggregation of blood platelets by ADP and its reversal. Nature. 1962; 194: 972
• 25 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 Haemostas 1984; 51: 157-164
• 26 Ahn YS, Harrington WJ, Simon SR, Mylvaganam R, Pall LM, So AG. Danazol for the treatment of idiopathic thrombocytopenic purpura. N Eng J Med 1983; 308: 1396-1399
• 27 Landa L, de Leon A. Estudio clinio acerca del efecto del andro- stanopirazal sobre el funcionamiento del higado. Rev Invest Clin 1962; 14: 431-436
• 28 On file with Sterling Research Laboratories.
• 29 Jannuzzi C, Bassetti D, Frigerio G. Recherche cliniche controllate sull ’effetto di steroidi anabolizzante nell ’epatite virale. Minerva Med 1970; 61: 1902-1911