Platelet Counts and Aggregation Measures in the Incidence of Ischaemic Heart Disease (IHD)

Summary

Although studies in those who have already experienced clinical episodes of ischaemic heart disease (IHD) have suggested properties of platelets influencing recurrence, there is limited information on the value of platelet tests in predicting first episodes of IHD. One study has suggested that a raised platelet count and increased aggregability in response to adenosine diphosphate (ADP) may increase IHD incidence but the numbers of IHD events involved were small. The larger Northwick Park Heart Study (NPHS) included platelet count and both ADP and adrenaline-induced aggregation and this paper presents their associations with subsequent IHD. Platelet counts were performed in 1369 white NPHS men aged between 40 and 64 at recruitment, of whom 181 subsequently experienced a major episode of IHD over a follow-up period of 16.1 years. Platelet count was unrelated to the incidence of IHD. ADP-induced aggregation was performed in a random sample of 740 men in whom 66 IHD events occurred during the subsequent 10.1 years, aggregability being measured both as ED50, the ADP dose at which aggregation occurred at half its maximum velocity, and also as EMR, the maximum rate of aggregation achieved. Neither measurement showed any association with IHD incidence, nor did similar measurements in 460 men in whom adrenaline-induced aggregation was also carried out. There are at least three possible explanations for the lack of any association between the measures of aggregability used and IHD. First, the large within-person variability of platelet aggregation tests may make the demonstration of any associations difficult, though the study had reasonable power to show effects with ADP. Secondly, the tests used may not be a valid index of the contribution of platelet function to thrombosis and IHD. However, the clear effect of several personal and demographic influences associated with IHD on the tests used brings this explanation into question. Thirdly, the role of platelets in thrombogenesis may be determined mainly by plasma influences such as fibrinogen, rather than by intrinsic properties of platelets themselves. Platelet counts within the physiological range and the aggregation tests used in this and in some other studies are of no value as indices of the risk of first episodes of IHD.

• References

• 1 Meade TW, Vickers MV, Thompson SG, Stirling Y, Haines AP, Miller GJ. Epidemiological characteristics of platelet aggregability. BMJ 1985; 290: 428-432
• 2 Elwood PC, Beswick AD, Sharp DS, Yarnell JWG, Rogers S, Renaud S. Whole blood impedance platelet aggregometry and ischaemic heart disease. Arteriosclerosis 1990; 10: 1032-1036
• 3 Trip MD, Cats VM, van CapelleFJL, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 1990; 322: 1549-1554
• 4 Martin JF, Bath PMW, Burr ML. Influence of platelet size on outcome after myocardial infarction. Lancet 1991; 338: 1409-1411
• 5 Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn PF. Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation 1991; 84: 613-617
• 6 Meade TW, Brozovic M, Chakrabarti RR, Haines AP, Imeson JD, Mellows S, Miller GJ, North WRS, Stirling Y, Thompson SG. Haemostatic function and ischaemic heart disease: principal results of the Northwick Park Heart Study. Lancet 1986; 02: 533-537
• 7 Public health in Europe. No. 5: myocardial infarction community registers. Copenhagen, Denmark: World Health Organization; 1977
• 8 Vickers MV, Thompson SG. Sources of variability in dose response platelet aggregometry. Thromb Haemost 1985; 53: 219-220
• 9 Meade TW, Cooper JA, Stirling Y, Howarth DJ, Ruddock V, Miller GJ. Factor VIIIA, ABO blood group and the incidence of ischaemic heart disease. BrJ Haematol 1995; 84: 601-607
• 10 Thompson SG, Vickers MV. Methods in dose response platelet aggregometry. Thromb Haemost 1985; 53: 216-218
• 11 Hopkins A. BMDP 2L: Survival analysis with covariates – Cox models. In: Dixon WJ. ed BMDP statistical software. Berkeley: University of California Press; 1988: 719-743
• 12 Saniabadi AR, Lowe GDO, Barbenel JC, Forbes CD. A comparison of spontaneous platelet aggregation in whole blood with platelet rich plasma: additional evidence for the role of ADP. Thromb Haemost 1984; 51: 115-118
• 13 Begent NA, Zawilska M, Bom GVR. Effect of ADP-utilising enzymes on the arterial bleeding time in rats and rabbits. Br J Haematol 1982; 50: 317-325
• 14 Nurden P, Savi P, Heilmann E. et al. An inherited bleeding disorder linked to a defective interaction between ADP and its receptor on platelets. J Clin Invest 1995; 95: 1612-1622
• 15 Meade TW, Vickers MV, Thompson SG, Seghatchian MJ. The effect of physiological levels of fibrinogen on platelet aggregation. Thrombos Res 1985; 38: 527-534