Granger C B, Hirsch J, Califf R M, Col J, White H D, Betriu A, Woodlief L H, Lee K L, Bovill E G, Simes R J, Topol E J
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Circulation. 1996 Mar 1;93(5):870-8. doi: 10.1161/01.cir.93.5.870.
Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes.
Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin.
Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.
尽管静脉注射肝素在溶栓治疗后普遍使用，但很少有报告探讨抗凝程度与临床结局之间的关系。我们在全球应用链激酶和t-PA治疗闭塞冠状动脉（GUSTO-I）试验中，对29656例患者的活化部分凝血活酶时间（aPTT）进行了检测，并分析了aPTT与患者基线特征和临床结局之间的关系。
静脉注射肝素，先给予5000 U的负荷剂量，随后初始输注速度为1000 U/h，并调整剂量以使aPTT达到60至85秒的目标值。在溶栓给药后6、12和24小时采集aPTT。24小时时较高的aPTT与较低的患者体重密切相关（P<0.00001），同时也与年龄较大、女性以及不吸烟相关（所有P<0.0001）。在12小时时，与30天最低死亡率、卒中率和出血率相关的aPTT为50至70秒。aPTT与随后再梗死风险之间存在意外的直接关系。在静脉注射肝素停药后的最初10小时内，再梗死出现聚集现象。
尽管aPTT与临床结局之间的关系在一定程度上受到基线预后特征的影响而混淆，但发现aPTT高于70秒与更高的死亡、卒中、出血和再梗死可能性相关。这些发现表明，在未得到其他证实之前，我们应将溶栓治疗后静脉注射肝素的aPTT范围50至70秒视为最佳范围。
