Clotting Mechanisms in Patients with Hypertriglyceridemia during Therapy with Anabolic or Progestational Drugs

Helen I. Glueck; Charles J. Glueck

doi:10.1055/s-0038-1647789

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1973; 29(02): 499-509
DOI: 10.1055/s-0038-1647789

Original Article

Schattauer GmbH

Clotting Mechanisms in Patients with Hypertriglyceridemia during Therapy with Anabolic or Progestational Drugs

Helen I. Glueck M. D.

¹Department of Internal Medicine, University of Cincinnati College of Medicine, the General Clinical Research Center, and the Cincinnati General Hospital

,

Charles J. Glueck M. D.

¹Department of Internal Medicine, University of Cincinnati College of Medicine, the General Clinical Research Center, and the Cincinnati General Hospital

› Author Affiliations

Abstract

Summary

Effects of synthetic steroids with progestational and androgenic-anabolic activity (Norethindrone Acetate and Oxandrolone) on coagulation parameters and plasma lipids were studied in 20 patients with familial types III, IV and V hyperlipoproteinemia. Prior to therapy there was a relatively uniform elevation of fibrinogen (284 mg %) and esterase prothrombin (64 U/ml). On therapy mean fibrinogen fell sharply to 223 mg % (short-term) and 195 mg % long-term. There were no increments in other clotting factors, and levels of factor VII and X were decreased on drug in several patients who initially had abnormally high levels. The fall in fibrinogen on therapy did not correlate with concurrent decrements in cholesterol or triglyceride. In hypertriglyceridemic patients predisposed to coronary or peripheral vascular thrombosis, Norethindrone and Oxandrolone appear to ameliorate rather than potentiate any tendency to “hypercoagulability”.

Full Text

References

References
1 Astrxjp T, Beakman P, Levy R. I, Fredrickson D. S. 1970; Hyperlipoproteinemia and Fibrinolysis. Circulation 42: 49.
2 Astrup T, Wright I. S. 1968. Blood Coagulation, Thrombosis and Female Hormones. J. F. Mitchell Foundation; Washington, D. C.:
3 Bolton C. H, Hampton J. R, Mitchell J. R. A. 1968; Effect of oral contraceptive agents on platelets and plasma phospholipids. Lancet 02: 1336.
4 Born G. V. R, Cross M. J. 1962; Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 927.
5 Brakman P, Albrechtsen O. K, Astrup T. 1967; Blood Coagulation, fibrinolysis and contraceptive hormones. Journal of the American Medical Association 199: 69.
6 Chakrabarti R, Fearnley G. R. 1968; Effects of clofibrate on fibrinolysis, platelet stickiness, plasma-fibrinogen and serum-cholesterol. Lancet 02: 1007.
7 Chakrabarti R, Hocking E. D, Fearnley G. R, Mann R. D, Atwell T. N, Jackson D. 1968; Fibrinolytic activity and coronary artery disease. Lancet 01: 987.
8 Chauncy N. Y. 1964. Total cholesterol procedure, N-24A. In: Autoanalyzer Manual. Technicon Instruments Corp; New York.:
9 Davidson J. F, Lochead M, McDonald G. A, McNicol G. P. 1972; Fibrinolytic enhancement by Stanozolol: A double blind trial. British Journal of Haematology 22: 543.
10 Dugdale M, Masi A. 1969; Effects of oral contraceptives on blood clotting. Second report on the oral contraceptives. Advisory Committee on Obstetrics and Gynecology, Food and Drug Administration August, 1969; 43.
11 Epstein S. E, Rosing D. R, Brakman P, Redwood D. R, Astrup T. 1970; Impaired fibrinolytic response to exercise in patients with type IV hyperlipoproteinemia. Lancet 02: 631.
12 Fredrickson D. S, Levy R. I, Lees R. S. 1967; Fat transport in lipoproteins. An integrated approach to mechanisms and disorders. New England Journal of Medicine, 276, 32, 94, 148 215: 273.
13 Glueck C. J. 1971; Effects of Oxandrolone on plasma triglycerides and post-heparin lipolytic activity in patients with types III, IV and V familial hyperlipoproteinemia. Metabolism 20: 691.
14 Glueck C. J, Levy R. I, Fredrickson D. S. 1971; Norethindrone Acetate, post-heparin lipolytic actitiy and plasma triglycerides in patients with familial types I, III, IV, and V hyperlipoproteinemia. Annals of Internal Medicine 75: 345.
15 Glueck C. J, Scheel D, Fishback J, Steiner P. 1972; Progestagens, anabolic androgenic compounds and estrogens. Effects on triglycerides and post-heparin lipolytic enzymes. Lipids 07: 110.
16 Glueck H. I, Mackenzie M, Glueck C. J. 1972; Crystalline IgG protein in multiple myeloma: Identification effects on coagulation and on lipoprotein metabolism. Journal of Laboratory and Clinical Medicine 79: 731.
17 Glueck H. I, Sutherland J. 1961; Inherited factor VII defect in a Negro family. Pediatrics 27: 204.
18 Glueck H. I, Wachman J. 1970; A TAMe micromethod for the measurement of esterase prothrombin. American Journal of Clinical Pathology 54: 239.
19 Howie P. W, Mallison A. C, Prentice C. R. M, Horne C. H. W, McNicol G. P. 1970; Effect of combined estrogen-progestin oral contraceptives, oestrogen and progestin on antiplasmin and antithrombin activity. Lancet 02: 1329.
20 Inman W. H. W, Vessey M. P. 1968; Investigations of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of childbearing age. British Medical Journal 02: 193.
21 Inman W. H. W, Vessey M. P. 1967; Oral contraceptives and thromboembolic disease. Journal of the College of General Practitioners 13: 267.
22 Kessler G, Lederer H. 1966. Flourometric measurement of triglycerides. In: Kress L. T. (ed.) Automation in Analytical Chemistry. Mediad Inc; New York: 341.
23 Langdell R. D, Wagner R. H, Brinkhous K. M. 1965. Determination of the partial thromboplastin time. In: Tocantins L, Kazal L. A. (eds.), Blood Coagulation, Hemorrhage, Thrombosis. Grune and Stratton, Inc; New York: 103.
24 Lees R. S, Hatch F. T. 1963; Sharper separation of lipoprotein species by paper electrophoresis in albumin containing buffer. Journal of Laboratory and Clinical Medicine 61: 518.
25 Malhotra O. P, Carter J. R. 1966; A simple method of preparing substrate for factor X assay. Federation Proceedings 25: 256.
26 Mannucci P. M, Pareti F, Maggi C. A, Diaguardi M. 1971; Effect of Ciba 13, 437-Su on serum cholesterol and triglycerides, plasma fibrinogen, fibrinolysis and platelet adhesiveness in patients with ischaemic heart disease. Atherosclerosis 13: 1.
27 Quick A. J. 1966. Hemorrhagic Disease and Thrombosis. Lea and Febiger; Philadelphia: 391.
28 Ratnoff O. D, Menzie C. 1951; A new method for the determination of fibrinogen in small samples of plasma. Journal of Laboratory and Clinical Medicine 37: 316.
29 Reimers H. J, Schmahl F. W, Huth K, Lasch H. G. 1972; Blutgerinnung, insbesondere Thrombocytenumsatz, bei Hyperlipo proteinamien. Klinische Wochenschrift 50: 12.
30 Second Report on the oral Contraceptives. 1969. Advisory Committee of Obstetrics and Gynecology. Food and Drug Administration; Washington, D. C., August: 1969.
31 Sise H. 1968. Anovulatory hormones and blood coagulation. In: Astrup T, Wright I. S. (eds.) Blood Coagidation, Thrombosis and Female Sex Hormones. J. F. Mitchell Foundation; Washington, D. C: 19.
32 Snedecor G. W, Cochran W. G. 1967. Statistical methods, 6th edition. Iowa State College Press; Ames, Iowa: 59.
33 Sokal R. R, Rohlf J. (ed) 1969. Kruskall- Wallis Test. In: Biometry, the Principles and Practice of Statistics in Biologic Research. W. H. Freeman and Co; San Francisco: 387.
34 Stefanini M, Dameshek W. 1962. The hemorrhagic disorders. A clinical and therapeutic approach. Grune and Gratton Inc; New York: 451.
35 Vessey M. P, Doll R. 1969; Investigation of a relationship between oral contraceptives and thromboembolic disease, a further report. Birtish Medical J ournal 02: 651.
36 Wessler S, Yin E. T. 1968; Experimental hypercoagulable state induced by factor X- Comparison of activated and nonactivated forms. J ournal of Laboratory and Clinical Medicine 72: 256.