Innere Abt 3, Universitaetsklinikum Heidelberg, Heidelberg, Germany.
Clin Appl Thromb Hemost. 2011 Oct;17(5):549-55. doi: 10.1177/1076029610382651. Epub 2010 Sep 11.
Monitoring of direct inhibitors of thrombin (DTI) is critical for their safe and effective use as anticoagulants. We examined samples containing several concentrations of argatroban or lepirudin in reconstituted standard human plasma and plasma from medical outpatients and intensive care patients. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) were determined using automated analyzers. Ecarin clotting time (ECT) was measured using a 10 IU/mL dilution of ecarin in 0.05 mol/L CaCl(2). Calibration curves were approximately linear for TT and ECT in samples containing argatroban and lepirudin, respectively. Activated partial thromboplastin curves reached a plateau at DTI concentrations ≥2 µg/mL, suggesting that the aPTT may not reliably detect overdosing. Prothrombin time increased exponentially. A broad range of clotting times was seen in patient samples with all tests suggesting that individual morbidity and therapies may strongly influence test results and may lead to underestimation of DTI doses.
监测直接凝血酶抑制剂（DTI）对于它们作为抗凝剂的安全有效使用至关重要。我们检查了含有几种浓度的阿加曲班或来匹卢定的复溶标准人血浆和门诊及重症监护患者血浆样本。使用自动分析仪测定凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）和凝血酶时间（TT）。使用在 0.05mol/L CaCl2 中的 10IU/mL 埃卡林稀释液测量蛇静脉酶凝结时间（ECT）。TT 和 ECT 在含有阿加曲班和来匹卢定的样本中分别具有近似线性的校准曲线。aPTT 曲线在 DTI 浓度≥2μg/mL 时达到平台，这表明 aPTT 可能无法可靠地检测到过量。PT 呈指数增加。所有检测均显示患者样本中的凝血时间范围很宽，这表明个体发病率和治疗方法可能会强烈影响检测结果，并可能导致低估 DTI 剂量。
