Abstract
BackgroundThrombin is a key protease in coagulation also implicated in complex pathology including atherosclerosis. To address the role of thrombin in relation to myocardial infarction (MI) we explored thrombin generation analysis in plasma from patients and controls that had participated in the Glasgow MI Study (GLAMIS).MethodsThrombin generation at 1 and 2 pM TF and with and without thrombomodulin (TM) was performed on plasmas from 356 subjects (171 cases, 185 age and sex matched controls) from GLAMIS collected between 3 and 9 months after the MI event.ResultsAlthough thrombin generation was slightly delayed in cases (lag time increased from 3.3 to 3.6 min) at the highest trigger, the overall potential to generate thrombin was increased by 7% for the ETP and by 15% for the peak height (both at the 1 pM TF trigger) in cases. Addition of TM did not reveal differences. Furthermore, an increased thrombin generation was associated with MI [normalized ETP: adjusted OR for the highest percentile = 2.4 (95% CI 1.3–4.5) and normalized peak height: adjusted OR = 2.6 (1.3–5.0)] at the lowest trigger; normalized ETP and peak height being 2.1 (1.1–3.8) and 2.0 (1.0–4.1) at the higher 2 pM trigger.ConclusionIn GLAMIS, patients with a previous MI had an increased thrombin generation compared to controls. The absence of a clear difference in TM reduction suggests an unaltered anticoagulant activity in these patients. Further research is needed in order to unravel the underlying mechanisms of enhanced thrombin generation after MI.
Highlights
In the pathogenesis of acute myocardial infarction (MI) common risk factors for atherosclerosis as well as hemostatic factors are important determinants
Since in vitro thrombin generation analysis is typically aimed at establishing the potential to generate thrombin in a given plasma aliquot, rather than the actual amount of thrombin formed in vivo in the acute phase, we set out to compare thrombin generation in plasma samples collected in individuals with previous myocardial infarction and matched controls, collected in the Glasgow Myocardial Infarction Study (GLAMIS)
Thrombin generation triggered with 1 pM tissue factor (TF) was delayed in cases as indicated by a prolongation of the lag time from 5.6 min for controls to almost 6.0 min (p.0.05) for cases, whereas the overall potential to generate thrombin was significantly increased in cases
Summary
In the pathogenesis of acute myocardial infarction (MI) common risk factors for atherosclerosis as well as hemostatic factors are important determinants. Contra-intuitively, endogenous thrombin potential (ETP), one of the main parameters derived from thrombin generation analysis, tended to be lower in those who had a subsequent recurrent arterial vascular event, which in conjunction with an elevated level of D-dimer yielded a significant risk for recurrence of 5.8 [3]. These analyses were confined to plasma samples collected during the acute phase of AMI.
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