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

作     者：Hoffmeister, HM Kastner, C Szabo, S Beyer, ME Helber, U Kazmaier, S Baumbach, A Wendel, HP Heller, W 

作者机构：Univ Tubingen Med Klin Abt Innere Med 3 D-72076 Tubingen Germany 

出 版 物：《AMERICAN JOURNAL OF CARDIOLOGY》 (美国心脏病学杂志)

年 卷 期：2000年第86卷第3期

页      面：263-268页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Boehringer Mannheim 

主　　题：抗凝血酶Ⅲ/药物作用 抗凝血酶Ⅲ/代谢 剂量效应关系 药物 用药计划表 药物疗法 联合 纤维蛋白/药物作用 纤维蛋白/代谢 纤维蛋白溶解/药物作用 纤维蛋白溶解药/投药和剂量 止血/药物作用 激肽释放酶类/药物作用 激肽释放酶类/代谢 心肌梗死/血液 心肌梗死/药物疗法 肽水解酶类/药物作用 肽水解酶类/代谢 纤溶酶/代谢 前瞻性研究 重组蛋白质类/投药和剂量 复发 凝血酶/代谢 血栓溶解疗法 组织型纤溶酶原激活物/投药和剂量 成年人 老年人 老年人 80以上 女(雌)性 人类 男(雄)性 中年人 

摘      要：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 mu g/L (reteplase) and 19,522 +/- 2,381 mu g/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.