Download PDF
Thromb Haemost 1987; 57(01): 020-024
DOI: 10.1055/s-0038-1651054
Original Articles
Schattauer GmbH Stuttgart

Treatment of Hereditary Protein C Deficiency with Stanozolol

A W Broekmans
1   The Haemostasis and Thrombosis Research Unit, University Hospital Leiden, The Netherlands
,
J Conard
2   The Laboratoire Central d’Hématologie (Head: Prof. M. Samama), Hôtel Dieu, Paris, France
,
R G van Weyenberg
3   The Regional Hospital “West-Friesland”, Hoorn, The Netherlands
,
M H Horellou
2   The Laboratoire Central d’Hématologie (Head: Prof. M. Samama), Hôtel Dieu, Paris, France
,
C Kluft
4   The TNO: Gaubius Institute for Cardiovascular Research, Leiden, The Netherlands
,
R M Bertina
1   The Haemostasis and Thrombosis Research Unit, University Hospital Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 17 June 1986

Accepted after revision 14 October 1986

Publication Date:
06 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints

Summary

Five type I protein C deficient male patients received 5 mg stanozolol b.i.d. during 4 weeks. After four weeks of treatment plasma protein C activity increased from 0.42 to 0.74 U/ml and protein C antigen from 0.49 to 0.75 U/ml. This approximately 1.6 fold increase in plasma protein C was accompanied by an increase in factor II antigen (1.5 fold), factor V activity (1.6 fold), factor X antigen (1.1 fold), antithrombin III antigen (1.3 fold) and heparin cofactor II antigen (1.5 fold), while the concentration of factor VII, factor VIII, and factor IX activity, and of protein S antigen remained unchanged. Prothrombin fragment F1+2, measured in two patients, increased 1.3 fold. In addition to its effect on procoagulant and anticoagulant factors stanozolol had profibrinolytic effects, reflected in an increase in tPA activity and in the concentration of plasminogen. These data indicate that in type I protein C deficient patients stanozolol increases the concentrations of both procoagulant and anticoagulant factors and favours fibrinolysis. The efficacy of stanozolol in preventing thrombotic disease in type I protein C deficient patients, however, remains to be established. During the four weeks of stanozolol treatment no thrombotic manifestations were observed in the protein C deficient patients.

Keywords

Protein C deficiency - Thrombosis - Stanozolol
 

  • References

  • 1 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68: 1370-1373
    CrossrefPubMedGoogle Scholar
  • 2 Broekmans AW, Veltkamp JJ, Bertina RM. Congenital protein C deficiency and venous thrombo-embolism. A study of three Dutch families. New Engl J Med 1983; 309: 340-344
    CrossrefPubMedGoogle Scholar
  • 3 Pabinger-Fasching I, Bertina RM, Lechner K, Niessner H, Kominger C. Protein C deficiency in two Austrian families. Thromb Haemostas 1983; 50: 810-813
    PubMedGoogle Scholar
  • 4 Horellou MH, Conard J, Bertina RM, Samama M. Congenital protein C deficiency and thrombotic disease in nine French families. Br Med J 1984; 289: 1285-1287
    CrossrefPubMedGoogle Scholar
  • 5 Broekmans AW. Hereditary protein C deficiency. Haemostasis 1985; 15: 233-240
    PubMedGoogle Scholar
  • 6 Broekmans AW, Bertina RM, Loeliger EA, Hofmann V, Klingemann HG. Protein C and the development of skin necrosis during anticoagulant therapy. Thromb Haemostas 1983; 49: 251
    PubMedGoogle Scholar
  • 7 McGehee WG, Klotz TA, Epstein DJ, Rapaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Int Med 1984; 100: 59-60
    CrossrefPubMedGoogle Scholar
  • 8 Samama M, Horellou MH, Soria J, Conard J, Nicolas G. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at the initiation of oral anticoagulant treatment. Thromb Haemostas 1984; 51: 132-133
    PubMedGoogle Scholar
  • 9 Pabinger-Fasching I, Deutsch E. Protein C deficiency in Austria. Sem Thromb Hemost 1985; 11: 347-351
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Loeliger EA, Broekmans AW. Drugs affecting blood clotting, fibrinolysis and hemostasis. In: Meyler’s Side Effects of drugs. Dukes MNG. (ed). Amsterdam, Excerpta Medica; 1984. 10 648-693
    Google Scholar
  • 11 Kluft C, Bertina RM, Preston FE, Malia RG, Blarney SL, Lowe G DO, 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
    CrossrefPubMedGoogle Scholar
  • 12 Bertina RM, Broekmans AW, Linden I Kvan der, Mertens K. Protein C deficiency in a Dutch family with thrombotic disease. Thromb Haemostas 1982; 48: 1-5
    PubMedGoogle Scholar
  • 13 Bertina RM, Broekmans AW, Krommenhoek-van Es C, Van Wijngaarden A. The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency. Thromb Haemostas 1984; 51: 1-5
    PubMedGoogle Scholar
  • 14 Bertina RM, Van Wijngaarden A, Reinalda-Poot J, Poort SR, Born V JJ. Determination of plasma protein S - the protein cofactor of activated protein C. Thromb Haemostas 1985; 53: 268-272
    PubMedGoogle Scholar
  • 15 Friberger P, Knos M. Plasminogen determination in human plasma. In: Chromogenic peptide substrate. Scully M, Kakkar VV. (eds). 128-139 Churchill Livingstone; Edinburgh: 1979
    Google Scholar
  • 16 Verheijen JH, Mullaart E, Chang G TG, Kluft C, Wijngaards G. A simple, sensitive spectrophotometric assay for extrinsic (tissue-type) plasminogen activator applicable to measurement in plasma. Thromb Haemostas 1982; 48: 266-269
    PubMedGoogle Scholar
  • 17 Verheijen JH, Chang G TG, Kluft C. Evidence for the occurrence of a fast-acting inhibitor for tissue-type plasminogen activator in human plasma. Thromb Haemostas 1984; 51: 392-395
    PubMedGoogle Scholar
  • 18 Kluft C, Vellenga E, Brommer E JP, Wijngaards G. A familial haemorrhagic diathesis in a Dutch family: an inherited deficiency of α2-antiplasmin. Blood 1982; 59: 1169-1180
    PubMedGoogle Scholar
  • 19 Kluft C, Preston FE, Malia RG, Bertina RM, Wijngaards G, Greaves M, Verheijen JH, Dooijewaard G. Stanozolol-induced change in fibrinolysis and coagulation in healthy adults. Thromb Haemostas 1984; 51: 157-164
    PubMedGoogle Scholar
  • 20 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilizing radioimmunoassays for the F2/F1 + 2 fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-1097
    PubMedGoogle Scholar
  • 21 Mannucci PM, Bottasso B, Sharon C, Tripodi A. Treatment with stanozolol of type I protein C deficiency in an Italian family. La Ricerca Clin Lab 1984; 14: 673-680
    PubMedGoogle Scholar
  • 22 Broekmans AW, Bertina RM. Hereditary protein C deficiency. In: Biochemical and Medical Aspects of Protein C. Witt I. (ed). Walter de Gruyter; Berlin: 1985: 93-105
    Google Scholar
  • 23 Gonzalez R, Alberca I, Sala N, Vicente V. Protein C deficiency - response to danazol and DDAVP. Thromb Haemostas 1985; 53: 320-322
    PubMedGoogle Scholar
  • 24 Gruppo RA, Francis RB, Marlar RA, Leimer P, Silberstein EB. Discordant protein C deficiency resulting from possible double heterozygosity and its response to danazol. Thromb Haemostas 1985; 54: 142 (Abstr)
    PubMedGoogle Scholar
  • 25 Madanes AE, Farber M. Danazol. Ann Intern Med 1985; 96: 625-630
    PubMedGoogle Scholar
  • 26 Tollefsen DM, Blank M. Detection of a new heparin-dependent inhibitor of thrombin in human plasma. J Clin Invest 1981; 68: 589-596
    CrossrefPubMedGoogle Scholar
  • 27 Walker FJ. The regulation of activated protein C by a new protein: a possible function for bovine protein S. J Biol Chem 1980; 255: 5521-5524
    PubMedGoogle Scholar
  • 28 Blarney SL, McArdle BM, Burns P, Carter DC, Lowe G DO, Forbes CD. A double-blind trial of intramuscular stanozolol in the prevention of postoperative deep vein thrombosis following elective abdominal surgery. Thromb Haemostas 1984; 51: 71-74
    PubMedGoogle Scholar
  • 29 Winter JH, Fenech A, Bennett B, Douglas AS. Prophylactic antithrombotic therapy with stanozolol in patients with familial antithrombin III deficiency. Br J Haematol 1984; 57: 527-537
    CrossrefPubMedGoogle Scholar
  • 30 Jarrett P EM, Morland M, Browse NL. The complications of stanozolol and their clinical management. In: Progress in chemical fibrinolysis and thrombolysis. Davidson JF. (ed). Edinburgh: 1979. Churchill Livingstone; 317-321
    Google Scholar