Failure of Thrombin Generation Markers to Triage Patients Presenting with Chest Pain

Abstract

Thrombin generation (TG) is an important pathogenic factor in acute coronary syndromes including acute myocardial infarction (AMI). Since the diagnostic utility of TG remains uncertain we sought to determine whether markers of TG may triage patients presenting to the Emergency Department with chest pain. Soluble plasma levels of prothrombin fragment 1+2 (F₁₊₂), and thrombin/antithrombin III complexes (TAT) were determined by ELISA in 80 patients presenting with chest pain to the Emergency Department and compared with 20 controls. There were no differences in TG markers between patients with non-cardiac chest pain and healthy controls. Patients with unstable angina (UA), and congestive heart failure (CHF) did not differ from controls with respect to F₁₊₂, and TAT was elevated in UA patients (6.05 ± 1.15 ng/ml, p = 0.033) when compared with controls (3.34 ± 0.20 ng/ml). Contrary to expectations, TAT levels at presentation with AMI were well below the concentrations observed in patiens with UA and CHF. Moreover, plasma F₁₊₂ levels were significantly lower than in healthy controls (0.84 ± 0.10 ng/ml versus 1.22 ± 0.11, p = 0.026). At the time of presentation to the Emergency Department, F₁₊₂ and TAT failed to suitably triage patients with chest pain. The surprisingly low levels of TG markers in AMI patients before applying intensive therapy and reperfusion strategies deserves further investigation.

Increased plasma levels of soluble platelet glycoprotein V in patients with acute myocardial infarction

“…These chronological factors could explain the lack of detection of soluble GPV at a later time, and the window of 24 h in the inclusion criterion was probably too large. Other markers of thrombin generation have likewise been reported as failing to identify patients with unstable angina [6]. Plasma VWF increased significantly in the group of acute myocardial infarction with ST segment elevation, in agreement with previous studies [7].…”

Patients with Coronary Artery Disease who Present with Chest Pain Have Significantly Elevated Platelet Contractile Force and Clot Elastic Modulus

“…Chronic ongoing thrombin generation is known to occur in atherosclerosis (23,28) and in conditions such as diabetes that are known to be risk factors for coronary artery disease. Although we did not measure thrombin-antithrombin (TAT) in our patients, it has been reported to be elevated in patients with angina (29,30). In like manner, inhibition of glycoprotein IIb/IIIa exposure (Ticlopidine or Clopidogrel) or direct receptor blockade by glycoprotein IIb/IIIa antagonists (abciximab, Eptifibatide, Tirofiban) decreases PCF.…”

Biomarkers and Exercise Training: A Possible Missing Link between Physical Activity and Mortality Benefit in Patients with Heart Failure

“…Moreover, post-AMI patients with heart failure exhibited significantly higher TAT and fibrinopeptide A levels on days 3, 5 and 7 after the coronary event as compared to patients without heart failure [103]. Recent data from our laboratory demonstrate that although TG markers are not particularly useful in triaging the origin of chest pain, heart failure patients exhibited higher levels of F 1+2 and TAT than the noncardiac chest pain group [106].…”