Marmur J D, Merlini P A, Sharma S K, Khaghan N, Torre S R, Israel D H, Ardissino D, Ambrose J A
Department of Medicine, Mount Sinai School of Medicine New York, New York 10029.
J Am Coll Cardiol. 1994 Nov 15;24(6):1484-91. doi: 10.1016/0735-1097(94)90144-9.
The aim of this study was to investigate the relation between coronary atherosclerotic plaque injury and activation of the coagulation cascade.
Thrombus formation after atherosclerotic plaque disruption has been implicated in the pathogenesis of atherosclerosis, unstable angina and myocardial infarction.
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.
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.
Markers of thrombin generation and activity can be collected safely and assayed accurately in heparinized blood withdrawn through an angioplasty catheter.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.
本研究旨在探讨冠状动脉粥样硬化斑块损伤与凝血级联激活之间的关系。
动脉粥样硬化斑块破裂后的血栓形成与动脉粥样硬化、不稳定型心绞痛和心肌梗死的发病机制有关。
在经皮冠状动脉腔内血管成形术（PTCA）前、术中及术后即刻，检测冠状动脉血液中凝血酶生成（凝血酶原片段F1+2）和凝血酶活性（纤维蛋白肽A）的生化标志物。在证实肝素化后通过血管成形术导管采血不会人为升高这些标志物的血浆水平后，对26例患者在球囊扩张前病变近端和远端以及球囊扩张后病变远端采集冠状动脉样本。
血管成形术前病变近端测得的F1+2血浆水平（中位数0.47 nmol/升，95%可信区间[CI] 0.40至0.50）在血管成形术后显著升高（中位数0.55 nmol/升，95% CI 0.46至0.72，p = 0.001）。相比之下，血管成形术前病变近端测得的血浆纤维蛋白肽A水平（中位数2.0 ng/ml，95% CI 1.3至2.2）与血管成形术后测得的水平相似（中位数1.8 ng/ml，95% CI 1.3至3.0，p =无显著性差异）。根据血管成形术前病变近端和远端采集样本获得的值确定了测定间变异的正常范围后，7例患者（27%）的F1+2血浆水平显著升高。这7例患者中有5例血浆纤维蛋白肽A显著升高。血管成形术后血管造影显示有夹层、充盈缺损或模糊的病变比无这些特征的病变产生更多的凝血酶。
通过血管成形术导管采集的肝素化血液中，可安全收集并准确测定凝血酶生成和活性的标志物。在接受血管成形术的相当一部分患者中，冠状动脉狭窄的球囊扩张会增加冠状动脉内凝血酶的生成和活性。
