Increased Activity of Vitamin K-Dependent Clotting Factors in Human Hyperlipoproteinaemia – Association with Cholesterol and Triglyceride Levels

Summary

Levels of blood coagulation factors, cholesterol and triglyceride were measured in human plasma. Prothrombin was significantly elevated in type Ha hyperlipidaemia; prothrombin and factors VII, IX and X in type lib; and prothrombin and factors VII and IX in type V. Multiple regression analysis showed significant correlation between the levels of these plasma lipids and the vitamin K-dependent clotting factors (prothrombin, factors VII, IX and X). Higher cholesterol levels were associated with higher levels of prothrombin and factor X while higher triglyceride levels were associated with higher levels of these as well as factors VII and IX. Prothrombin showed a significant cholesterol-triglyceride interaction in that higher cholesterol levels were associated with higher prothrombin levels at all levels of triglyceride, with the most marked effects in subjects with higher triglyceride levels. Higher prothrombin levels were noted in subjects with high or moderately elevated (but not low) cholesterol levels. Ultracentrifugation of plasma in a density of 1.21 showed activity for prothrombin and factors VII and X only in the lipoprotein-free subnatant fraction. Thus, a true increase in clotting factor protein was probably present. The significance of the correlation between levels of vitamin K-dependent clotting factors and plasma lipids remains to be determined.

• References

• 1 BrozoviĆ M, Stirling Y, Harricks C, North W. R. S, Meade T. W. 1974; Factor VII in an industrial population. British Journal of Haematology 28: 381.
• 2 Carvalho A. C. A, Colman R. W, Lees R. S. 1974; Platelet function in hyperlipoproteinemia. New England Journal of Medicine 290: 434.
• 3 Cohen J, Cohen P. 1975. Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences. Lawrence Erlbaum Associates; Hillsdale, New Jersey.:
• 4 Editorial. 1973; Long-term blood abnormalities in thrombosis. Lancet II: 133.
• 5 Ellis B. C, Stransky A. 1961; A quick and accurate method for the determination of fibrinogen in plasma. Journal of Laboratory and Clinical Medicine 58: 477.
• 6 Goldstein J. L, Hazzard W. R, Schrott H. G, Bierman E. L, Motulsky A. G, Levinski M. J, Campbell E. D. 1973; Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. Journal of Clinical Investigation 52: 1533.
• 7 Hamilton P. J, Allardyce M, Ogston D, Dawson A. A, Douglas A. S. 1974; The effect of age upon the coagulation system. Journal of Clinical Pathology 27: 980.
• 8 Hoyer L. W. 1972; Immunologic studies of antihemophilic factor (AHF, factor VIII). IV. Radioimmunoassay of AHF antigen. Journal of Laboratory and Clinical Medicine 80: 822.
• 9 Kim W. M, Merskey C, Deming Q. B, Adel H. N, Wolinsky H, Clarkson T. B, Lofland H. B. 1976; Hyperlipidemia, hypercoagulability, and accelerated thrombosis: studies in congenitally hyperlipidemic rats and in rats and monkeys with induced hyperlipidemia. Blood 47: 275.
• 10 Laurell C.-B. 1972; Electroimmuno Assay. Scandinavian Journal of Clinical and Laboratory Investigation 29 (Suppl. 124) 21.
• 11 Macfarlane D. E, Stibbe J, Kirby E. P, Zucker M. B, Grant R. A, McPherson J. 1975; A method for assaying von Willebrand factor (ristocetin cofactor). Thrombosis et Diathesis Haemorrhagica 34: 306.
• 12 Manual of Laboratory Methods. 1974. Lipid Research Clinics Program. Department of Health, Education, and Welfare Publications, National Institutes of Health; 75-628 19.
• 13 Marcus A. J, Ullman H. L, Safier L. B, Ballard H. S. 1962; Platelet phosphatides. Their fatty acid and aldehyde composition and activity in different clotting systems. Journal of Clinical Investigation 41: 2198.
• 14 Merskey C, Johnson A. J, Lalezari P. 1972; Increase in fibrinogen and fibrin-related antigen in human serum due to in vitro lysis of fibrin by thrombin. Journal of Clinical Investigation 51: 903.
• 15 Owren P. A, Aas K. 1951; The control of dicumarol therapy and the quantitative determination of prothrombin and proconvertin. Scandinavian Journal of Clinical and Laboratory Investigation 3: 201.
• 16 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.
• 17 Shanberge J. N, Matsuoka T, Fukui H. 1967; A simple method for the preparation of a substrate for a one-stage factor V assay. American Journal of Clinical Pathology 47: 533.
• 18 Sorbye O, Phillips F. C, Lundberg W. O. 1971; Potential function of cholesterol in blood coagulation: Amplification of phospholipid thromboplastic activity. Lipids 6: 139.
• 19 Sterzing P. R, Barton P. G. 1973; The influence of cholesterol on the activity of phospholipids in blood coagulation: Requirements for a liquid-crystalline lipid phase. Chemistry and Physics of Lipids 10: 137.
• 20 Weiss H. J, Hoyer L. W, Rickles F. R, Varma A, Rogers J. 1973; Quantitative assay of a plasma factor deficient in von Willebrand’s disease that is necessary for platelet aggregation. Relationship to factor VIII procoagulant activity and antigen content. Journal of Clinical Investigation 52: 2708.