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The central role of platelet activation in determining the severity of acute coronary syndromes
  1. S Kennon1,
  2. C P Price2,
  3. P G Mills1,
  4. M Macey3,
  5. J Cooper4,
  6. H Clarke2,
  7. A D Timmis1
  1. 1Department of Cardiology, Bart’s and the London NHS Trust, London, UK
  2. 2Department of Clinical Biochemistry, Bart’s and the London NHS Trust
  3. 3Department of Haematology, Bart’s and the London NHS Trust
  4. 4MRC Epidemiology and Medical Care Unit, Charterhouse Square, London, UK
  1. Correspondence to:
    Dr S Kennon, Cardiac Catheterisation Laboratory, St Vincents Private Campus, 59–61 Victoria Parade, Fitzroy, Melbourne, Victoria 3065, Australia;

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Recent observational studies in acute coronary syndromes have shown that factors influencing the degree of platelet activation also influence the mode of presentation. Prior aspirin treatment and smoking—with directionally opposite effects on platelet function—were found to be independently associated with unstable angina and myocardial infarction, respectively.1 However, the few studies involving direct measurement of activation parameters in acute coronary syndromes have not provided a consensus regarding this.2,3 To clarify whether there is differential activation in unstable angina and acute myocardial infarction we have prospectively assessed platelet activation in a cohort of patients presenting with acute coronary syndromes by using a light scattering technology to determine mean platelet component, a marker of platelet degranulation.


Consecutive patients admitted to an east London hospital with acute coronary syndromes were recruited. Myocardial infarction was diagnosed if two of the following criteria were fulfilled: (a) cardiac chest pain lasting at least 30 minutes; (b) ⩾ 0.1 mV ST elevation in at least one standard lead or ⩾ 0.2 mV ST elevation in two or more contiguous chest leads; and (c) creatine kinase concentration ⩾ 400 IU/l (upper limit of reference range 200 IU/l). ECG criteria were not required for the diagnosis of unstable angina; however, patients were recruited only if they fulfilled criteria for Braunwald class 3B unstable angina. Patients admitted with acute coronary syndromes within the previous 21 days were excluded, as were those who had undergone percutaneous coronary intervention in the previous six months.

Blood was taken on admission—before antithrombotic treatment—for platelet activation status (mean platelet component) and troponin I determination.

Whole blood samples were taken into vacutainers (Becton Dickinson) containing EDTA. Samples were analysed, between 30–240 minutes after venesection, for determination of mean platelet component with the ADVIA 120 haematology system (Bayer Corporation, Tarrytown, New York, USA).

Troponin I concentrations were measured with a commercially available assay (Bayer Immuno 1 Analyser, Bayer Plc, UK) and a cut off point of 0.1 μg/l.

Variables significant (p ⩽ 0.05) on univariate analysis were selected for testing in a stepwise multiple logistic regression model. In view of the relatively small sample size exact logistic regression analysis was used to check the ordinary analysis.


The study group comprised 89 patients, 25 with acute myocardial infarction and 64 with unstable angina. The groups were similar as regards age and sex distribution. A previous history of acute coronary syndromes or revascularisation was recorded more commonly in patients with unstable angina whose admission medication was significantly more likely to include drugs for secondary prevention.

Pretreatment with aspirin was less frequent and smoking more frequent in acute myocardial infarction than in unstable angina (table 1). Mean (SD) platelet component was lower in acute myocardial infarction than in unstable angina (246.7 (15.8) v 258.6 (13.8) g/l, p = 0.001), reflecting significantly greater platelet activation. This difference persisted when the unstable angina cohort was limited to 48 patients at high risk of future cardiac events defined by troponin I concentration > 0.1 μg/l or ischaemic ST/T changes on the presenting ECG (246.7 (15.8) v 258.1 (14.4) g/l, p = 0.016).

Table 1

Univariate predictors of diagnosis

In logistic regression analysis, the odds of presenting with acute myocardial infarction were reduced by 91% (odds ratio (OR) 0.09, 95% confidence interval (CI) 0.02 to 0.32, p < 0.0001) by pretreatment with aspirin and by 64% (OR 0.36, 95% CI 0.18 to 0.72, p = 0.004) for an increase in mean platelet component by one standard deviation. A history of hypertension, which reduced the odds of myocardial infarction by 75% (OR 0.25, 95% CI 0.06 to 1.02, p = 0.05), was the only other variable with independent predictive power. The exact logistic regression for the model gave similar results though the effect of hypertension was weaker (data not shown). If the time between venesection and analysis of blood was forced into the logistic regression analysis, mean platelet component remained a significant predictor of clinical presentation (OR 0.48, 95% CI 0.27 to 0.86, p = 0.01).


Our finding that mean platelet component is lower in acute myocardial infarction than in unstable angina, reflecting greater platelet activation, confirms the central role of thrombogenicity in the pathogenesis of acute coronary syndromes. Indeed, platelet activation was an independent predictor of the mode of presentation and, even in the subgroup of patients with unstable angina at high risk of future events, platelet activation was significantly lower than in those with myocardial infarction.

Some studies have not found a difference in platelet activation between unstable angina and myocardial infarction. However, Garlichs and colleagues2 found greater expression of the CD40 ligand in unstable angina than in myocardial infarction. This appears counterintuitive but may reflect greater hydrolysis and release of the ligand in myocardial infarction. Mathur and colleagues3 found a greater expression of P selectin in myocardial infarction than in unstable angina but also found that mean platelet volume, which is directly related to platelet activity, was greater in unstable angina than in myocardial infarction. Fundamental differences in platelet biology between patients with unstable angina and those with myocardial infarction were proposed as an explanation for these findings because platelets are anucleate and their size is predetermined at the time of thrombopoiesis. In the current study platelets were larger in those with acute myocardial infarction than in those with unstable angina. However, this difference was not significant, and it is unclear whether the diagnosis specific differences in mean platelet component were predetermined or reactive. Studies in apparently healthy volunteers have shown greater platelet activation in those with a strong family history of coronary artery disease4 and in those who subsequently die from cardiac causes.5 This is consistent with the degree of platelet activation being causally related to outcome. Certainly, we identified no factors that accounted for the differences in platelet activation that were independent of smoking habit and pretreatment with cardiac drugs that are known to influence platelet function.

Mean platelet component, as determined by the ADVIA 120 haematology system, is derived by using a laser source and light scattering technology. It reflects the granularity of platelets and is inversely related to the expression of CD62P. Because the assay measures granularity, it has the advantage over standard flow cytometric techniques of avoiding the need for sample preparation with antisera, which is complex, time consuming, expensive, and a source of error.

This study has shown diagnosis specific differences in platelet activation in acute coronary syndromes. The data therefore provide direct evidence to support the hypothesis that platelet activation at the time of plaque disruption is a major determinant of clinical presentation.


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