急性心肌梗死患者接受溶栓治疗和肝素治疗时的凝血酶生成、抑制及临床结局：GUSTO-I试验结果。GUSTO-I止血亚研究组。链激酶和组织型纤溶酶原激活剂在闭塞冠状动脉中的全球应用。

Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial. GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.

作者信息

Granger C B, Becker R, Tracy R P, Califf R M, Topol E J, Pieper K S, Ross A M, Roth S, Lambrew C, Bovill E G

机构信息

Duke Clinical Research Institute, Durham, North Carolina.

出版信息

J Am Coll Cardiol. 1998 Mar 1;31(3):497-505. doi: 10.1016/s0735-1097(97)00539-1.

DOI:10.1016/s0735-1097(97)00539-1

PMID:9502626

Abstract

OBJECTIVES

We sought to assess the effects of antithrombotic therapy after thrombolysis for acute myocardial infarction on markers of thrombin generation and activity and to determine the relation of these markers with clinical outcomes.

BACKGROUND

Thrombin activation and generation often occur with thrombolysis for acute myocardial infarction. Antithrombotic regimens have been developed to reduce the resulting thrombotic complications.

METHODS

We sampled plasma markers of thrombin generation and activity after thrombolysis in 292 patients. We assessed the relations of these markers with clinical outcomes at 30 days.

RESULTS

Fibrinopeptide A (FPA), a marker of thrombin activity toward fibrinogen, was elevated at baseline (12.3 ng/ml) and increased to 18.4 ng/ml by 90 min after streptokinase and subcutaneous heparin treatment. With intravenous heparin, this increase was attenuated, but intravenous heparin did not prevent thrombin generation, as measured by prothrombin fragment 1.2 (F1.2). Heparin level, measured by anti-Xa activity, correlated with activated partial thromboplastin time (aPTT, r = 0.62 to 0.67). Thrombin activity, measured by FPA, was as closely related to aPTT as to the heparin level. Baseline levels of F1.2 were significantly related to the risk of death or reinfarction at 30 days (p = 0.008); values 12 h after enrollment also were related to 30-day mortality (p = 0.05).

CONCLUSIONS

Although intravenous heparin partly suppresses the increased thrombin activity associated with thrombolysis, it does not inhibit thrombin generation. The aPTT was as good a measure of suppression of thrombin activity as the heparin level itself. Hematologic markers of thrombin generation were found to be related to the subsequent risk of thrombotic events.

摘要

目的

我们试图评估急性心肌梗死溶栓治疗后抗血栓治疗对凝血酶生成及活性标志物的影响，并确定这些标志物与临床结局的关系。

背景

急性心肌梗死溶栓治疗时常发生凝血酶激活及生成。已制定抗血栓治疗方案以减少由此导致的血栓形成并发症。

方法

我们对292例患者溶栓后的血浆凝血酶生成及活性标志物进行了采样。我们评估了这些标志物与30天时临床结局的关系。

结果

纤维蛋白肽A（FPA），一种凝血酶对纤维蛋白原活性的标志物，在基线时升高（12.3 ng/ml），链激酶和皮下肝素治疗90分钟后升至18.4 ng/ml。使用静脉肝素后，这种升高有所减弱，但通过凝血酶原片段1.2（F1.2）测量，静脉肝素并不能阻止凝血酶生成。通过抗Xa活性测量的肝素水平与活化部分凝血活酶时间（aPTT，r = 0.62至0.67）相关。通过FPA测量的凝血酶活性与aPTT的关系和与肝素水平的关系一样密切。F1.2的基线水平与30天时死亡或再梗死风险显著相关（p = 0.008）；入院12小时时的值也与30天死亡率相关（p = 0.05）。