急性心肌梗死中的溶栓治疗：链激酶和阿替普酶治疗方案促凝作用的比较，重点关注激肽释放酶系统和纤溶酶

Thrombolytic therapy in acute myocardial infarction: comparison of procoagulant effects of streptokinase and alteplase regimens with focus on the kallikrein system and plasmin.

作者信息

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

机构信息

Medizinische Universitätsklinik, Abt Innere Medizin III, Tübingen, Germany.

出版信息

Circulation. 1998 Dec 8;98(23):2527-33. doi: 10.1161/01.cir.98.23.2527.

DOI:10.1161/01.cir.98.23.2527

PMID:9843458

Abstract

BACKGROUND

Thrombolytic therapy in patients with acute myocardial infarction (AMI) is hampered by procoagulant effects. In vitro studies have indicated that plasmin stimulation activates the kallikrein-contact-phase system, resulting in thrombin activation. This prospective comparative study was designed to examine the procoagulant effects of streptokinase or alteplase in AMI.

METHODS AND RESULTS

Sixty-one patients with AMI received 1.5 million U of streptokinase or front-loaded alteplase (up to 100 mg) and systemic heparin. Twenty-four patients with AMI and no thrombolytic therapy and 30 control subjects were examined for comparison. Molecular markers of thrombin, plasmin activation, and coagulation activities were determined before therapy and serially for up to 10 days. Moderate thrombin (initial thrombin-antithrombin [TAT] complex 18+/-5 versus 4+/-0.3 microg/L, P<0.05) and kallikrein (up to 45+/-4 versus 30+/-1 U/L at 3 hours, P<0.01) activation occurs in patients with AMI. D-Dimers are increased (P<0.01), and plasmin is stimulated (P<0.01). Streptokinase and alteplase increase TAT to 50+/-17 and 51+/-18 microg/L at 3 hours and to 50+/-17 and 33+/-14 microg/L at 6 hours, respectively (P<0.01). Kallikrein activity is elevated (P<0. 01) to 76+/-5 and 71+/-7 U/L at 3 hours and 64+/-6 and 47+/-5 U/L by streptokinase and alteplase, respectively, at 6 hours. Reductions in fibrinogen and increases in D-dimers and plasmin-antiplasmin complexes are more marked (P<0.05 and 0.01) after streptokinase versus alteplase. Correlations were found among TAT, kallikrein activity, and plasmin activation (P<0.01).

CONCLUSIONS

The data indicate a more marked procoagulant action of the streptokinase regimen compared with front-loaded alteplase, thus supporting the hypothesis of a plasmin-mediated kallikrein activation with consecutive procoagulant action in vivo.

摘要

背景

急性心肌梗死（AMI）患者的溶栓治疗受到促凝作用的阻碍。体外研究表明，纤溶酶刺激可激活激肽释放酶-接触相系统，导致凝血酶激活。本前瞻性比较研究旨在探讨链激酶或阿替普酶在AMI中的促凝作用。

方法与结果

61例AMI患者接受150万U链激酶或负荷剂量阿替普酶（最大100mg）及全身肝素治疗。24例未接受溶栓治疗的AMI患者和30例对照者作为比较。在治疗前及连续10天内测定凝血酶、纤溶酶激活及凝血活性的分子标志物。AMI患者出现中度凝血酶（初始凝血酶-抗凝血酶[TAT]复合物18±5 vs 4±0.3μg/L，P<0.05）和激肽释放酶激活（3小时时高达45±4 vs 30±1U/L，P<0.01）。D-二聚体升高（P<0.01），纤溶酶受到刺激（P<0.01）。链激酶和阿替普酶在3小时时分别将TAT升高至50±17和51±18μg/L，6小时时分别升高至50±17和33±14μg/L（P<0.01）。链激酶和阿替普酶在3小时时分别将激肽释放酶活性升高至76±5和71±7U/L，6小时时分别升高至64±6和47±5U/L（P<0.01）。与阿替普酶相比，链激酶治疗后纤维蛋白原降低、D-二聚体和纤溶酶-抗纤溶酶复合物增加更为明显（P<0.05和0.01）。发现TAT、激肽释放酶活性和纤溶酶激活之间存在相关性（P<0.01）。