达比加群etexilate,利伐沙班和阿哌沙班(DOAC)被广泛使用,在某些临床情况下需要测量其浓度。靶特异性测定是可用的,但是关于它们的性能,特别是在它们准确地测量低和高浓度的能力方面存在有限的信息。
目标:定义,在一项多中心研究中,日常实践中DOAC测量的精度和准确性。
方法:15份血浆样本(由Hyphen-Biomed提供)加标5种盲化浓度的达比加群,利伐沙班或阿哌沙班(目标0-40-100-250-500ng/mL,通过HPLC-MS/MS测量的实际浓度),被送到30个止血实验室.DOAC浓度,使用局部试剂在每个样品中测量一次PT和aPTT。实验室间精密度取决于其变异系数(CV),而准确性则取决于其偏差。
结果:在30个实验室中使用4个达比加群和5个利伐沙班/阿哌沙班校准测定法在3个分析仪上进行了464个DOAC测量。对于浓度≥100ng/mL,实验室间CV低于18%,浓度~40ng/mL时更高;所有药物和浓度的偏差均低于8%。在无DOAC样品中,除一个值(达比加群:35ng/mL)外,其他浓度均低于定量下限.根据浓度,发现利伐沙班和阿哌沙班浓度值之间存在显着差异。PT和aPTT比率显示出对阿哌沙班的低敏感性。
结论:我们的结果表明,校准的DOAC测定法可以可靠地测量各种药物浓度,尽管改进他们的表现是必要的,特别是用于测量低浓度。
Dabigatran etexilate, rivaroxaban and apixaban (DOACs) are widely used and measurement of their concentration is desirable in certain clinical situations. Target-specific assays are available but limited information exists on their performance especially in their ability to accurately measure low and high concentrations.
OBJECTIVE: To define, in a multicenter
study, the precision and accuracy of DOAC measurements in daily practice.
METHODS: 15 plasma samples (kindly provided by Hyphen-Biomed) spiked with 5 blinded concentrations of dabigatran, rivaroxaban or apixaban (targeted 0-40-100-250-500ng/mL, actual concentrations measured by HPLC-MS/MS), were sent to 30 haemostasis laboratories. DOAC concentration, PT and aPTT were measured once in each sample using local reagents. Interlaboratory precision was determined by its coefficient of variation (CV) and accuracy by its bias.
RESULTS: 464 DOAC measurements were performed in the 30 laboratories using 4 dabigatran and 5 rivaroxaban/apixaban calibrated assays on 3 analysers. Inter-laboratory CVs were below 18% for concentrations ≥100ng/mL, and higher for concentrations ~40ng/mL; biases were below 8% for all drugs and concentrations. In DOAC-free samples, concentrations were all below the lower limit of quantification except for one value (dabigatran: 35ng/mL). Depending on the concentrations, significant differences were found between reagents in rivaroxaban and apixaban concentration values. PT and aPTT ratios displayed a low sensitivity to apixaban.
CONCLUSIONS: Our results suggest that calibrated DOAC assays allow the reliable measurement of a wide range of drug concentrations, even though improvement of their performances is necessary, especially for measuring low concentrations.