在急性心肌梗死中，与激肽释放酶 - 接触相系统以及双推注瑞替普酶和前端负荷阿替普酶溶栓时纤溶酶生成相关的纤维蛋白特异性和促凝血作用。

Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction.

作者信息

Hoffmeister H M, Kastner C, Szabo S, Beyer M E, Helber U, Kazmaier S, Baumbach A, Wendel H P, Heller W

机构信息

Medizinische Universitätsklinik, Abteilung Innere Medizin III, Eberhard-Karls Universität Tübingen, Tübingen, Germany.

出版信息

Am J Cardiol. 2000 Aug 1;86(3):263-8. doi: 10.1016/s0002-9149(00)00911-5.

DOI:10.1016/s0002-9149(00)00911-5

PMID:10922430

Abstract

This study was undertaken to compare the effects of reteplase and alteplase regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI). Thrombolytic treatment in patients with AMI is hampered by paradoxical procoagulant effects that favor early reocclusion. In vivo data comparing this effect and the fibrin specificity of double-bolus reteplase and front-loaded alteplase regimens are not available. In a prospective, randomized study, 50 patients with AMI were either treated with double bolus (10 + 10 U) reteplase or with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset. Thirty apparently healthy persons served as controls. Molecular markers of coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical thrombin activation at 3 hours after initiation of therapy was comparable between reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L) caused significantly elevated kallikrein activity at 3 hours after adminstration (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/- 28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3 hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml). Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01) increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase) and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of thrombolytic therapy proved less marked fibrin specificity of the reteplase regimen (in vivo) compared with front-loaded alteplase. Both regimens have a moderate procoagulant effect without differences in activation of the kallikrein system.

摘要

本研究旨在比较瑞替普酶和阿替普酶治疗方案对急性心肌梗死（AMI）患者止血和纤溶的影响。AMI患者的溶栓治疗因矛盾的促凝作用而受到阻碍，这种促凝作用有利于早期再闭塞。目前尚无比较双剂量瑞替普酶和先予负荷量阿替普酶治疗方案的这种作用及纤维蛋白特异性的体内数据。在一项前瞻性随机研究中，50例AMI患者在症状发作6小时内，要么接受双剂量（10 + 10 U）瑞替普酶治疗，要么接受先予负荷量阿替普酶（最大剂量100 mg）治疗。30名明显健康的人作为对照。连续5天对凝血和纤溶的分子标志物进行检测。治疗开始后3小时，瑞替普酶和阿替普酶组的矛盾性凝血酶激活情况相当。给药后3小时，瑞替普酶（65±5 U/L）和阿替普酶（72±8 U/L）组的激肽释放酶活性显著升高（与对照组30±1 U/L相比，p<0.01）。瑞替普酶的纤维蛋白特异性较低（p<0.05），给药3小时后纤维蛋白原降至122±27 mg/dl，而阿替普酶组为224±28 mg/dl（与对照组相比，p<0.01和p<0.05）。给药3小时后，瑞替普酶组的D - 二聚体水平（5459±611 ng/ml）高于阿替普酶组（3445±679 ng/ml）（两者与对照组243±17 ng/ml相比，p<0.01）。两种治疗方案在给药3小时时纤溶酶生成（纤溶酶 - 抗纤溶酶复合物）均显著增加（p<0.01），瑞替普酶组为27079±3964 μg/L，阿替普酶组为19522±2381 μg/L。溶栓治疗开始后3小时的数据表明，与先予负荷量阿替普酶相比，瑞替普酶治疗方案（体内）的纤维蛋白特异性较低。两种治疗方案均有中等程度的促凝作用，激肽释放酶系统激活无差异。