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Thrombin generation in human coronary arteries after percutaneous transluminal balloon angioplasty
J D Marmur1, P A Merlini, S K Sharma
1Department of Medicine, Mount Sinai School of Medicine New York, New York 10029.
Insights
Percutaneous transluminal coronary angioplasty significantly increases thrombin generation in patients with coronary atherosclerosis. This study demonstrates that markers of thrombin generation can be safely measured during angioplasty, revealing increased coagulation activation after plaque injury.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Interventional Cardiology
Background:
- Plaque disruption in atherosclerosis is linked to thrombus formation, contributing to unstable angina and myocardial infarction.
- Understanding the coagulation cascade's role in plaque injury is crucial for managing acute coronary syndromes.
Purpose of the Study:
- To investigate the relationship between coronary atherosclerotic plaque injury and the activation of the coagulation cascade.
- To assess thrombin generation and activity markers in coronary blood during angioplasty.
Main Methods:
- Biochemical markers of thrombin generation (prothrombin fragment F1+2) and activity (fibrinopeptide A) were measured.
- Coronary blood samples were collected before, during, and after percutaneous transluminal coronary angioplasty (PTCA) in 26 patients.
- Validation of blood withdrawal techniques confirmed no artifactual elevation of markers in heparinized patients.
Main Results:
- Plasma levels of prothrombin fragment F1+2 significantly increased post-angioplasty (p = 0.001).
- Fibrinopeptide A levels showed no significant change, though a subset of patients had increased levels.
- Angiographic features of plaque injury, such as dissection or filling defects, correlated with increased thrombin generation.
Conclusions:
- Thrombin generation and activity markers can be reliably collected and assayed via angioplasty catheters in heparinized patients.
- Balloon angioplasty of coronary stenoses demonstrably increases thrombin generation and activity in a significant portion of patients.
Objectives:
The aim of this study was to investigate the relation between coronary atherosclerotic plaque injury and activation of the coagulation cascade.
Background:
Thrombus formation after atherosclerotic plaque disruption has been implicated in the pathogenesis of atherosclerosis, unstable angina and myocardial infarction.
Methods:
Biochemical markers of thrombin generation (prothrombin fragment F1+2) and thrombin activity (fibrinopeptide A) were measured in coronary blood before, during and immediately after percutaneous transluminal coronary angioplasty. After demonstrating that blood withdrawal through an angioplasty catheter does not artifactually elevate the plasma levels of these markers in patients after heparinization, coronary artery samples were collected proximal and distal to the lesion before and distal to the lesion after balloon inflation in 26 patients.
Results:
Plasma levels of F1+2 measured proximal to the lesion before angioplasty (median 0.47 nmol/liter, 95% confidence interval [CI] 0.40 to 0.50) were significantly elevated after angioplasty (median 0.55 nmol/liter, 95% CI 0.46 to 0.72, p = 0.001). In contrast, plasma fibrinopeptide A levels measured proximal to the lesion before angioplasty (median 2.0 ng/ml, 95% CI 1.3 to 2.2) were similar to those measured after angioplasty (median 1.8 ng/ml, 95% CI 1.3 to 3.0, p = NS). After we defined a normal range of interassay variability on the basis of values obtained from samples drawn proximal and distal to the lesion before angioplasty, seven patients (27%) had a significant increase in F1+2 plasma levels. A significant increase in plasma fibrinopeptide A occurred in five of these seven patients. Lesions with dissection, filling defects or haziness on postangioplasty angiography were associated with more thrombin generation than lesions without these features.
Conclusions:
Markers of thrombin generation and activity can be collected safely and assayed accurately in heparinized blood withdrawn through an angioplasty catheter. Balloon dilation of coronary stenoses increases thrombin generation and activity within the coronary artery in a substantial subgroup of patients undergoing angioplasty.