Gosselin R C, Adcock D, Hawes E M, Francart S J, Grant R P, Moll S
Robert C. Gosselin, University of California Davis Health System, Pathology and Laboratory Medicine, 2315 Stockton Blvd, Room 2P344, Davis, CA 95821, USA, Tel.: +1 916 7342490, Fax: +1 916 7036775, E-mail:
Thromb Haemost. 2015 Jan;113(1):77-84. doi: 10.1160/TH14-04-0361. Epub 2014 Nov 20.
Suitable laboratory methodologies for quantifying the non-vitamin K oral anticoagulants (NOAC) include liquid chromatography-tandem mass spectrometry (LC-MS/MS) or drug-calibrated assays such as the dilute thrombin time for dabigatran or anti-Xa measurements for rivaroxaban. In situations when these tests are unavailable, it has been suggested that using commercial drug calibrators on APTT and PT assays would theoretically provide reagent sensitivity to these drugs. The purpose of this study was to determine whether commercial drug calibrators deliver similar reagent sensitivity information as samples from patients receiving dabigatran or rivaroxaban as part of their routine care. Two laboratory sites tested commercial calibrator material for dabigatran and rivaroxaban (Hyphen Biomedical) using PT and APTT reagents and data was compared to samples collected from patients taking NOACs that were quantified by LC-MS/MS. Correlation statistics and calculating the amount of drug required to double the clotting time of normal plasma were performed. All drug calibrator material correlated more strongly (R²> 0.95) for any reagent/drug combination than patient samples (R² ranged from 0.29-0.86). Dabigatran calibrator results and patient data were equivalent for SynthASil and PTT-A APTT reagents. The dabigatran and rivaroxaban calibrator material over-estimated drug sensitivity for all PT reagents when compared to sensitivity data calculated based on drug levels obtained by LC-MS/MS from patient samples. In conclusion, drug-specific calibrators overestimated reagent sensitivity which may underestimate in vivo drug concentration in a given patient. Further studies are required to assess whether this method of determining relative sensitivity of NOAC on routine coagulation assays should be recommended.
用于定量非维生素K口服抗凝剂（NOAC）的合适实验室方法包括液相色谱-串联质谱法（LC-MS/MS）或药物校准检测，如用于达比加群的稀释凝血酶时间或用于利伐沙班的抗Xa检测。在无法进行这些检测的情况下，有人建议在活化部分凝血活酶时间（APTT）和凝血酶原时间（PT）检测中使用商业药物校准物，理论上可以提供对这些药物的试剂敏感性。本研究的目的是确定商业药物校准物是否能提供与接受达比加群或利伐沙班常规治疗的患者样本相似的试剂敏感性信息。两个实验室地点使用PT和APTT试剂检测了达比加群和利伐沙班的商业校准物材料（Hyphen Biomedical），并将数据与从服用NOACs的患者收集的样本进行比较，这些样本通过LC-MS/MS进行定量。进行了相关性统计，并计算了使正常血浆凝血时间加倍所需的药物量。对于任何试剂/药物组合，所有药物校准物材料的相关性都比患者样本更强（R²>0.95），患者样本的R²范围为0.29-0.86。对于SynthASil和PTT-A APTT试剂，达比加群校准物结果与患者数据相当。与基于从患者样本中通过LC-MS/MS获得的药物水平计算的敏感性数据相比，达比加群和利伐沙班校准物材料在所有PT试剂上都高估了药物敏感性。总之，药物特异性校准物高估了试剂敏感性，这可能会低估给定患者体内的药物浓度。需要进一步研究以评估是否应推荐这种在常规凝血检测中确定NOAC相对敏感性的方法。
