Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays
Assessment of apixaban plasma levels by laboratory tests: suitability of three anti-Xa assays
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DOI：
10.1160/th13-06-0470
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发表时间：
2014-02-01
影响因子：
6.7
通讯作者：
Lecompte, Thomas
中科院分区：
文献类型：
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作者：
Gouin-Thibault, Isabelle;Flaujac, Claire;Lecompte, Thomas
虽然在接受阿哌沙班（一种直接Xa因子抑制剂）治疗的患者中不需要进行实验室监测，但在某些危急情况下，对其浓度进行评估是有用的。然而，关于其对凝血试验的影响和抗Xa测定法对其定量的适用性的数据很少。本研究的目的是确定适用于阿哌沙班浓度评估的实验室检查。在阿哌沙班加标血浆样本中进行凝血试验（PT和aPTT）和抗Xa试验。为了评估PT和aPTT对阿哌沙班的敏感性，我们进行了第一个单中心部分，浓度范围很宽（50- 1，000 ng/ml），大量试剂（20种试剂）和两个凝血仪（星星（R），Stago和ACL TOP（R），IL），第二个多中心部分涉及13个实验室，使用普通PT试剂（RecombiPlastin 2G（R））或当地PT和aPTT试剂。在多中心部分，使用了5份设盲阿哌沙班加标血浆样本（通过HPLC-MS/MS检查0/100/200/400/800 ng/ml）;使用3种抗Xa检测试剂、阿哌沙班校准品和质控品（Stago）测量阿哌沙班浓度。使用大量试剂进行的PT和aPTT试验显示，对阿哌沙班浓度范围较宽的灵敏度较低。使用10种试剂，双PT的浓度范围为400至1> 1，000 ng/ml。三种抗Xa检测试剂的实验室间精密度和准确度分别低于11%和12%。总之，尽管PT和aPTT检测灵敏度不足以检测阿哌沙班，但使用冻干阿哌沙班校准品和质控品检测的三种抗Xa检测试剂盒能够可靠地定量阿哌沙班的各种浓度。
While laboratory monitoring is not required in patients treated with apixaban, a direct factor-Xa inhibitor, assessment of its concentration is useful in some critical situations. However, few data are available on its 1 effect on coagulation tests and on the suitability of anti-Xa assays for its quantification. It was the objective of this study to identify laboratory tests suitable for apixaban concentration assessment. Coagulation tests -PT and aPTT- and anti-Xa assays were performed in apixaban-spiked plasma samples. To evaluate the sensitivity of PT and aPTT to apixaban, we conducted a first monocenter part, with a wide range of concentrations (50-1,000 ng/ml), a large panel of reagents (20 reagents), and two coagulometers (STAR (R), Stago and ACL TOP (R), IL), and a second multicenter part involving 13 laboratories using either a common PT reagent (RecombiPlastin2G (R)) or the local PT and aPTT reagents. In the multicentre part, five blinded apixaban-spiked plasma samples (0/100/200/400/800 ng/ml checked by HPLC-MS/MS) were used; apixaban concentrations were measured with three anti-Xa assays, apixaban calibrators and controls (Stago). PT and aPTT tests using a large; panel of reagents displayed a low sensitivity to a wide range of apixaban concentrations. The concentrations to double PT ranged from 400 to I >1,000 ng/ml with the 10 reagents. With the three anti-Xa assays, inter-laboratory precision and accuracy were below 11% and 12%, respectively. In conclusion, whereas PT and aPTT tests were not sensitive enough to detect apixaban, the three anti-Xa assays tested using lyophilised apixaban calibrators and controls allowed to reliably quantify a wide range of apixaban concentrations.