Mani Helen, Herth Natalie, Kasper Alexander, Wendt Thomas, Schuettfort Gundolf, Weil Yvonne, Pfeilschifter Waltraud, Linnemann Birgit, Herrmann Eva, Lindhoff-Last Edelgard
*Division of Vascular Medicine, Department of Internal Medicine, Goethe-University Hospital; †Cardio Health Center, Rossmarkt; ‡Department of Neurology, Goethe-University Hospital; and §Institute of Biostatistics and Mathematical Modelling, Goethe-University Hospital, Frankfurt/Main, Germany.
Ther Drug Monit. 2014 Oct;36(5):624-31. doi: 10.1097/FTD.0000000000000064.
This investigation was carried out with already available point-of-care testing (POCT) systems for coagulation parameters to evaluate the qualitative and semiquantitative determination of the time- and concentration-dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and dabigatran.
The whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined using the GEM PCL Plus coagulation system. Whole blood PT was also measured on the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent. Drug concentrations of rivaroxaban and dabigatran were determined with a chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good agreement with liquid chromatography coupled with tandem mass spectrometry measurements. POCT was performed in 27 consecutive patients who received rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran 110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after observed drug intake at steady state.
Two hours after observed rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was prolonged by an average of 64.5% in comparison with predose levels. Less differentiation was observed for rivaroxaban when the PT was measured on the CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%, respectively). After 2 hours observed dabigatran administration, the whole blood aPTT was comparable with plasma values and was prolonged by 23.5% in comparison with trough values. Significant concentration-dependent prolongations of the activated clotting time were observed to different extents for both direct anticoagulants.
Direct oral anticoagulants display variable ex vivo effects on different POCT-assays. POCT for aPTT is sensitive to increased concentrations of dabigatran, whereas the PT-POCT assessed with test systems such as the GEM PCL Plus may be helpful to measure the pharmacodynamic anticoagulant effects of rivaroxaban in emergency clinical situations.
本研究使用现有的即时检验（POCT）系统检测凝血参数，以评估直接口服抗凝剂利伐沙班和达比加群的时间和浓度依赖性抗凝作用的定性和半定量测定。
使用GEM PCL Plus凝血系统测定全血凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）和活化凝血时间（ACT）。还使用CoaguCheck XS仪器测定全血PT。此外，使用PT试剂Neoplastin Plus和STA APTT试剂在枸橼酸盐血浆中获得PT和aPTT值。利伐沙班和达比加群的药物浓度通过发色抗Xa测定法和血凝块测定法测定，据报道这两种方法与液相色谱-串联质谱测量结果具有良好的一致性。对27例连续接受每日一次10、15或20mg利伐沙班治疗的患者以及15例接受每日两次110或150mg达比加群治疗的患者进行了POCT检测。在给药前和稳态下观察到药物摄入后2小时采集血样。
在观察到利伐沙班给药2小时后，与给药前水平相比，GEM PCL Plus上测定的全血PT平均延长了64.5%。当在CoaguCheck XS仪器上或血浆中测量PT时，利伐沙班的差异较小（分别延长24.1%和36.8%）。在观察到达比加群给药2小时后，全血aPTT与血浆值相当，与谷值相比延长了23.5%。两种直接抗凝剂均观察到活化凝血时间在不同程度上有显著的浓度依赖性延长。
直接口服抗凝剂对不同的POCT检测显示出不同的体外效应。用于aPTT的POCT对达比加群浓度升高敏感，而使用GEM PCL Plus等检测系统评估的PT-POCT可能有助于在紧急临床情况下测量利伐沙班的药效学抗凝作用。
