Gosselin Robert C, Dager William E, King Jeffrey H, Janatpour Kim, Mahackian Kathleen, Larkin Edward C, Owings John T
Department of Pathology, University of California, Davis Medical Center, Sacramento, USA.
Am J Clin Pathol. 2004 Apr;121(4):593-9. doi: 10.1309/D79K-4YG7-8NTN-YY38.
Direct thrombin inhibitors (DTIs) represent a new class of promising anticoagulation agents. The DTIs frequently are used to provide initial anticoagulation, with long-term therapy requiring eventual transition to coumarins. Unfortunately, DTIs not only prolong the activated partial thromboplastin time but also can affect international normalized ratio (INR) values. We approximated the DTI effect on INRs by each drug to pooled plasma at concentrations between 0.1 and 1.2 microg/mL. We then concurrently tested these samples using 14 prothrombin time (PT) reagents. By using repeated measures analysis of variance, we found significant differences (P < .05) between the median INRs for lepirudin and argatroban for all PT reagents, between lepirudin and bivalirudin for all reagents except PT-Fibrinogen HS Plus (P = .07), and between bivalirudin and argatroban for all reagents except Thromborel S (P = .05). The DTI effect on INRs was dependent on drug, drug concentration, and reagent. Argatroban had the most effect on INRs, while lepirudin had the least effect. Reagents with a lower international sensitivity index were less affected by DTI; ThromboMax HS was the least sensitive PT reagent to any DTI.
直接凝血酶抑制剂（DTIs）是一类前景广阔的新型抗凝剂。DTIs常用于提供初始抗凝治疗，长期治疗最终需要过渡到使用香豆素类药物。不幸的是，DTIs不仅会延长活化部分凝血活酶时间，还会影响国际标准化比值（INR）。我们将每种药物在浓度为0.1至1.2微克/毫升之间时对INR的影响近似于混合血浆。然后，我们使用14种凝血酶原时间（PT）试剂同时检测这些样本。通过重复测量方差分析，我们发现对于所有PT试剂，来匹芦定和阿加曲班的INR中位数之间存在显著差异（P <.05）；对于除PT - 纤维蛋白原HS Plus（P =.07）之外的所有试剂，来匹芦定和比伐卢定之间存在显著差异；对于除Thromborel S（P =.05）之外的所有试剂，比伐卢定和阿加曲班之间存在显著差异。DTIs对INR的影响取决于药物、药物浓度和试剂。阿加曲班对INR的影响最大，而来匹芦定的影响最小。国际敏感指数较低的试剂受DTIs的影响较小；ThromboMax HS是对任何DTIs最不敏感的PT试剂。
