Background:
Myocardial ischemia at rest is typically associated with atherosclerotic
coronary artery disease, atherommous plaque
rupture, and intracoronary
thrombosis. In areas of advanced disease and
vascular injury, the extent of
thrombus is influenced largely by a delicate balance of procoagulant factors, favoring
thrombus initiation, growth, and development, and
anticoagulant factors, attempting to limit potentially flow-limiting
coronary thrombosis.
Thrombin, a 308
amino acid serine pretense, is considered the most patent procoagulant factor in the setting of acute vessel wall injury, playing an essential role in the conversion of
fibrinogen to
fibrin, accelerating the
prothrombinase complex, activating platelets, and stabilizing
fibrin polymers. The purpose of this study was to determine the relationship between electrocardiographic abnormalities and markers of
thrombin activity and generation among patients with
unstable angina and non-Q.wave
myocardial infarction. Mehtods and Results: In a study of 36 patients (59.1+/- 11.0 years) with
myocardial ischemia at rest participating in the Thrombolysis in
Myocardial Ischemia (TIMI) IIIB trial,
thrombin activity in plasma, as determined by
fibrinopeptide A (FPA),
prothrombin fragment 1.2 (F 1.2), and
thrombin-
antithrombin III complexes (TAT) concentrations, were found to be increased significantly when compared with healthy volunteers (p < 0.004).
Thrombin generation was also increased modestly compared with age-matched patients with stable
coronary artery disease undergoing elective cardiac catheterization. Given that,he surface 12-lead electrocardiogram (ECG) is frequently abnormal in patients with ischemic
chest pain at rest and represents a readily available, first-line diagnostic test for assessing disease activity and treatment response, we investigated whether ECG abnormalities and
thrombin activity/generation in plasma were correlated. Twenty-six patients (72%) had ECG changes compatible with
myocardial ischemia at the time of study entry, including 18 (50%) with newly inverted T waves (or pseudonormalization), 14 (39%) with reversible ST-segment depression, and 4 (11%) with transient (<30 minutes) ST-segment elevation. Within the predefined ECG groups there were no differences in plasma
thrombin activity between patients with and those without confirmed abnormalities. Similarly, there were no differences in either plasma
thrombin activity or generation between the predefined ECG groups. Conclusion: Although ECG abnormalities supporting the presence of
myocardial ischemia occur commonly in patients with
chest pain at rest, they do not correlate closely with markers of
thrombin activity and generation in plasma. The diagnostic and prognostic capabilities of these diagnostic tools, considered either alone or together, require further investigation.