Antithrombin III: Associations with Age, Race, Sex and Cardiovascular Disease Risk Factors

Summary

Antithrombin III (AT III) is a major inhibitor of blood coagulation, and hereditary deficiency is associated with venous thrombotic disease. The Atherosclerosis Risk in Communities (ARIC) Study, a prospective study of 15,800 middle-aged men and women, measured AT III in its baseline examination. AT III levels were significantly higher in women than men, and in blacks than whites. AT III decreased with age in men but increased with age in women. In age- and race-adjusted analyses, AT III was positively associated with smoking, HDL-cholesterol, triglycerides (men only), and in women, with diabetes and lipoprotein^). AT III was negatively associated with educational level, body mass index in men, and use of female hormones in women. Most of these associations were confirmed in multivariate analysis. These correlations between AT III and other risk factors must be considered when evaluating AT III as a risk factor for venous or arterial thrombosis.

• References

• 1 Gladson CL, Scharrer I, Hach V, Beck KH, Griffin JH. The frequency of type I heterozygous protein S and protein C deficiency in 141 unrelated young patients with venous thrombosis. Thromb Haemost 1988; 59: 18-22
• 2 Hirsh J, Piovella F, Pini M. Congenital antithrombin III deficiency. Incidence and clinical features. Am J Med 1989; 87 (Suppl. 03) 34S-38S
• 3 ARIC Investigators. The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives. Am J Epidemiol 1989; 129: 687-702
• 4 Papp AC, Hatzakis H, Bracey A, Wu KK. ARIC hemostasis study-I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. Thromb Haemost 1989; 61: 15-19
• 5 Chambless LE, McMahon R, Wu K, Folsom A, Finch A, Shen Y-L. Shortterm intraindividual variability in hemostasis factors: The ARIC Study. Ann Epidemiol 1992; 2: 723-733
• 6 Nagele U, Hagele EO, Sauer G, Wiedemann E, Lehmann P, Wahlefeld AW, Gruber W. Reagent for the enzymatic determination of serum total triglycerides with improved lipolytic efficiency. J Clin Chem Clin Biochem 1984; 22: 165-174
• 7 Siedel J, Hagele EO, Ziegenhorn J, Wahlefeld AW. Reagent for the enzymatic determination of total serum cholesterol with improved lipolytic efficiency. Clin Chem 1983; 29: 1075-1080
• 8 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
• 9 Warnick GR, Bertderson JM, Albers JJ. Quantitation of high-density-lipo-protein subclasses after separation by dextran sulfate and Mg²⁺ precipitation (Abstract). Clin Chem 1982; 28: 1574
• 10 Gaubatz JW, Cushing GL, Morrisett JD. Quantitation, isolation and characterization of human lipoprotein(a). Methods Enzymol 1986; 129: 167-185
• 11 Baecke JAH, Burema J, Frijters JER. A short questionnaire for the measurement of habitual physical activity in epidemiologic studies. Am J Clin Nutr 1982; 36: 936-942
• 12 SAS User’s Guide. Statistics. Cary NC. SAS Institute, Inc. 1985
• 13 Odegård OR, Fagerhol MK, Lie M. Heparin cofactor activity and antithrombin III concentration in plasma related to age and sex. Scand J Haematol 1976; 17: 258-262
• 14 odegård OR, Abildgaard U. Antithrombin III: Critical review of assay methods. Significance of variations in health and disease. Haemostasis 1978; 7: 127-134
• 15 Baker IA, Eastham R, Elwood PC, Etherington M, O’Brien JR, Sweetnam PM. Haemostatic factors associated with ischaemic heart disease in men aged 45 to 64 years. The Speedwell Study. Br Heart J 1982; 47: 490-494
• 16 Panicucci F, Sagripanti A, Conte B, Pinori E, Vispi M, Lecchini L. Antithrombin III, heparin cofactor and antifactor Xa in relation to age, sex and pathological condition. Haemostasis 1980; 9: 297-302
• 17 Fagerhol MK, Abildgaard U. Immunological studies on human antithrombin III. Influence of age, sex and use of oral contraceptives on serum concentration. Scand J Haematol 1970; 7: 10-17
• 18 Tait RC, Walker ID, Islam SIAM, McCall F, Conkie JA, Mitchell R, Davidson JF. Influence of demographic factors on antithrombin III activity in a healthy population. Br J Haematol 1993; 84: 476-480
• 19 Meade TW, North WRS, Chakrabarti R, Haines AP, Stirling Y. Population-based distributions of haemostatic variables. Br Med Bull 1977; 33: 283-288
• 20 Notelovitz M, Levenson I, McKenzie L, Lane D, Kitchens CS. The effects of low-dose oral contraceptives on coagulation and fibrinolysis in two high-risk populations: Young female smokers and older premenopausal women. Am J Obstet Gynecol 1985; 152: 995-1000
• 21 Prellwitz W, Schmitt K-F, Machner M, Schuster C-J, Weilemann L. Two automated methods for plasma antithrombin III compared, and the clinical significance of the result. Clin Chem 1982; 28: 2249-2253
• 22 Meade TW, Dyer S, Howarth DJ, Imeson JD, Stirling Y. Antithrombin III and procoagulant activity: Sex differences and effects of the menopause. Brit J Haematol 1990; 74: 77-81
• 23 Notelovitz M, Kitchens CS, Rappaport V, Coone L, Dougherty M. Menopausal status associated with increased inhibition of blood coagulation. Am J Obstet Gynecol 1981; 141: 149-152
• 24 Meilahn E, Kuller LH, Kiss JE, Matthews KA, Lewis JH. Coagulation parameters among pre- and postmenopausal women (Abstract). Am J Epidemiol 1988; 128: 908
• 25 Peterson RA, Krull PE, Finley P, Ettinger MG. Changes in antithrombin III and plasminogen induced by oral contraceptives. Am J Clin Pathol 1970; 53: 468-473
• 26 Meade TW, Haines AP, North WRS, Chakrabarti R, Howarth DJ, Stirling Y. Haemostatic, lipid, and blood-pressure profiles of women on oral contraceptives containing 50 μg or 30 μg oestrogen. Lancet 1977; 2: 948-951
• 27 Bounameaux H, Duckert F, Walter M, Bounameaux Y. The determination of antithrombin III. Comparison of six methods. Effect of oral contraceptive therapy. Thromb Haemost 1978; 39: 607-615
• 28 Gordon EM, Williams SR, Frenchek B, Mazur CA, Speroff L. Dose-dependent effects of postmenopausal estrogen and progestin on antithrombin III and factor XII. J Lab Clin Med 1988; 111: 52-56
• 29 Greig HBW, Notelovitz M. Natural oestrogens and antithrombin-III levels. Lancet 1975; 1: 412-413
• 30 Bonithon-Kopp C, Scarabin P-Y, Bara L, Castanier M, Jacqueson A, Roger M. Relationship between sex hormones and haemostatic factors in healthy middle-aged men. Atherosclerosis 1988; 71: 71-76
• 31 Rogers S, Yamell JWG, Fehily AM. Nutritional determinants of haemostatic factors in the Caerphilly study. Eur J Clin Nutr 1988; 42: 197-205
• 32 Winter JH, Bennett B, McTaggart F, Douglas AS. Lipoprotein fractions and antithrombin III consumption during clotting. Thromb Haemost 1982; 47: 236-238
• 33 Elder GE, Mayne EE, Daly JG, Kennedy AL, Hadden DR, Montgomery DA, Weaver JA. Antithrombin III activity and other coagulation changes in proliferative diabetic retinopathy. Haemostasis 1980; 9: 288-296
• 34 Borsey DQ, Prowse CV, Gray RS, Dawes J, James K, Elton RA, Clarke BF. Platelet and coagulation factors in proliferative diabetic retinopathy. J Clin Pathol 1984; 37: 659-664
• 35 Fuller JH, Keen H, Jarrett RJ, Omer T, Meade TW, Chakrabarti R, North WRS, Stirling Y. Haemostatic variables associated with diabetes and its complications. Br Med J 1979; 2: 964-966
• 36 Banerjee RN, Sahni AL, Kumar V, Arya M. Antithrombin III deficiency in maturity onset diabetes mellitus and atherosclerosis. Thromb Diath Hae-morrh 1974; 31: 339-345
• 37 Gamba G, Solerte SB, Grignani G, Pacchiarini L, Montani N, Ferrari E. Haemostatic variables, serum lipid abnormalities and vascular complications in diabetes mellitus: A 5-year follow-up study. Blut 1988; 56: 257-260
• 38 Hughes A, McVerry BA, Wilkinson L, Goldstone AH, Lewis D, Bloom A. Diabetes, a hypercoagulable state? Haemostatic variables in newly diagnosed type 2 diabetic patients. Acta Haematol 1983; 69: 254-259
• 39 Sowers JR, Tuck ML, Sowers DK. Plasma antithrombin III and thrombin generation time: Correlation with hemoglobin A₁ and fasting serum glucose in young diabetic women. Diabetes Care 1980; 3: 655-358
• 40 Ceriello A, Guigliano D, Dello Russo P, Tirelli A, Passariello N, Sgambato S. Metabolic control may alter antithrombin III activity but not its plasma concentration in diabetes: A possible role for nonenzymatic glycosylation. Diabetes Care 1986; 9: 32-35
• 41 Monnier L, Follea G, Mirouze J. Antithrombin III deficiency in diabetes mellitus: Influence on vascular degenerative complications. Horm Metab Res 1978; 10: 470-473
• 42 Gandolfo GM, De Angelis A, Torresi MV. Determination of antithrombin III activities by different methods in diabetic patients. Haemostasis 1980; 9: 15-19
• 43 Christe M, Fritschi J, Lammle B, Tran TH, Marbet GA, Berger W, Duckert F. Fifteen coagulation and fibrinolysis parameters in diabetes mellitus and in patients with vasculopathy. Thromb Haemost 1984; 52: 138-143
• 44 Patrassi GM, Picchinenna R, Vettor R, Cappellato G, Coccarielli D, Girolami A. Antithrombin III activity and concentration in diabetes mellitus. Thromb Haemost 1985; 54: 415-417
• 45 Zucker ML, Gomperts ED, Russel D, Joffe B, Feesey M, Kuschke R, Seftel A. Antithrombin functional activity after saturated and unsaturated fatty meals and fasting in normal subjects and some disease states. Thromb Res 1979; 15: 37-48
• 46 Meade TW, Cooper J, Miller GJ, Howard DJ, Stirling Y. Antithrombin III and arterial disease. Lancet 1991; 338: 850-351
• 47 Cortellaro M. for the PLAT Study Group. Antithrombin III and arterial disease. [Letter to the Editor]. Lancet 1991; 338: 1525-1526
• 48 Cortellaro M, Boschetti C, Cofrancesco E, Zanussi C, Catalano M, de Gaetano G, Gabrielli L, Lombardi B, Specchia G, Tremoli TE, della Volpe A, Polli E. the PLAT Study Group. The PLAT Study: Hemostatic function in relation to atherothrombotic ischemic events in vascular disease patients: Principal results. Arterioscler Thromb 1992; 12: 1063-1070
• 49 Wu KK, Folsom AR, Heiss G, Davis CE, Conlan MG, Barnes R. the ARIC Study Investigators. Association of coagulation factors and inhibitors with carotid artery atherosclerosis: Early results of the Atherosclerosis Risk in Communities (ARIC) Study. Ann Epidemiol 1992; 2: 471-480
• 50 Thompson SG, Martin JC, Meade TW. Sources of variability in coagulation factor assays. Thromb Haemost 1987; 58: 1073-1077