Thrombin Activity by Intrinsic Activation of Plasma In-Vitro Accelerates with Increasing Age of the Donor

Summary

Thrombotic diseases increase in incidence with advancing years and this might be partly due to an increased propensity for fibrin formation in older individuals. Accordingly we decided to investigate whether the time taken to generate 50% thrombin activity in vitro varied with the age of the plasma donor. Coagulation was initiated in defibrinated, diluted plasma by contact activation and thrombin activity measured using the chromogenic substrate, S2238. The rate of thrombin generation was assessed by measuring the time taken to reach 50% maximal activity (T50/s). There was a highly significant negative correlation between T50 and age, T50 declining from 93 s at 19 years to 71 s at 65 years (r = −0.637, p <0.0001). A strong negative correlation was demonstrated between T50 and FVII level (r = -0.415, p = 0.0007) and FVIII: C level (r = -0.465, p = 0.0001). Although FVII concentration correlated with age (r = 0.307, p = 0.014) no relationship was seen between age and FVIII :C. These data suggest that coagulation rates in plasma accelerate with age.

• References

• 1 Royal College of General Practitioners, Office of Population Censuses and Surveys and Department of Health and Social Security. Morbidity Statistics from General Practice 1971-2: Second National Study (Studies on Medical and Population Subjects No. 36). HMSO; London: 1979
• 2 Coon WW, Coller FA. Some epidemiological considerations of thromboembolism. Surg Gynaecol Obstet 1959; 109: 487-501
• 3 Egeberg O. Inherited antithrombin III deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530
• 4 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
• 5 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
• 6 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Ineson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Part heart study. Lancet 1986; ii: 533-537
• 7 Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med 1984; 311: 501-505
• 8 Balleisen L, Bailey J, Epping P-H, Schulte H, Van de Loo J. Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population. I. Baseline data on the relation to age, gender, body weight, smoking, alcohol, pill-using, and menopause. Thromb Haemostas 1985; 54: 475-479
• 9 Chakrabarti R, Brozovic M, North WRS, Stirling Y, Meade TW. Effects of age on fibrinolytic activity and factors V, VII and VIII. Proc R Soc Med 1975; 68: 15-16
• 10 Meade TW, Chakrabarti R, Haines AP, North WRS, Stirling Y. Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations. Br Med J 1979; 1: 153-156
• 11 Korsan-Bengtsen K, Wilhelmsen L, Tibblin G. Blood coagulation and fibrinolysis in a random sample of 788 men 54 years old. Thromb Diath Haemorrh 1972; 28: 89-98
• 12 Ibbotson SH, Tate GM, Hampton KK, Davies JA. Influence of increasing levels of high purity factor VIII on thrombin generation in vitro. Clin Sci 1990; 79 (23) pp l5 (abstr)
• 13 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. J Clin Invest 1987; 80: 1527-1534
• 14 Hemker HC, Willems GM, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes. Thromb Haemostas 1986; 56: 9-17
• 15 Austen DEG, Rhymes IL. Factor VII Assay. A Laboratory Manual of Blood Coagulation. Blackwell Scientific Publications; Oxford: 1975. p 49
• 16 Hardisty RM, MacPhearson JC. A one stage FVIII AHG assay and its use on venous and capillary plasma. Thromb Diath Haemorrh 1962; 7: 215-219
• 17 Thompson JM, Poller L. The activated partial thromboplastin time. In: Blood Coagulation and Haemostasis, a Practical Guide. Thompson JM. (ed).. 3rd ed. Churchill Livingstone; Edinburgh: 1985. pp 301-339
• 18 Teitel JM, Bauer KA, Lau HK, Rosenberg RD. Studies of the prothrombin activation pathway utilising radioimmunoassay for the F₂/F₁₊₂ fragment and thrombin-antithrombin complex. Blood 1982; 59: 1086-1097
• 19 Bauer KA, Kass BL, Beeler DL, Rosenberg RD. Detection of protein C activation in humans. J Clin Invest 1984; 74: 2033-2041
• 20 Nossel HL, Younger LR, Wilner GD, Procupez T, Canfield RE, Butler VP. Radioimmunoassay of human fibrinopeptide A. Proc Natl Acad Sci USA 1971; 68: 2350-2353
• 21 Davies JA. Detection of a pre-thrombotic state. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. (eds). 2nd ed. Churchill Livingstone; London: 1987. p 725