Clinical laboratory measurement of direct factor Xa inhibitors: Anti-Xa assay is preferable to prothrombin time assay
Clinical laboratory measurement of direct factor Xa inhibitors: Anti-Xa assay is preferable to prothrombin time assay
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DOI：
10.1160/th10-05-0328
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发表时间：
2010-12-10
影响因子：
6.7
通讯作者：
Shenker, Andrew
中科院分区：
文献类型：
--
作者：
Barrett, Yu Chen;Wang, Zhaoqing;Shenker, Andrew
阿哌沙班和其他Xa因子（FXa）抑制剂正处于预防和治疗血栓栓塞性疾病的临床开发后期。虽然常规监测将不需要，在某些情况下，药物水平的评估可能是helpful.本研究评估了市售的凝血酶原时间/国际标准化比值（PT/INR）和抗FXa活性测定，以测量FXa抑制剂在血浆中的适用性。使用加标4种FXa抑制剂（0- 2，000 ng/ml）的人血浆，在体外评价了12种PT（ISI 0.89-1.88）和3种抗Xa试验。在接受阿哌沙班治疗的静脉血栓栓塞（VTE）患者中评价了测定变异性和与药物血浆暴露的相关性。所有FXa抑制剂均延长PT;然而，测定灵敏度取决于所用促凝血酶原激酶试剂和检测的FXa抑制剂。为了实现PT翻倍，每种FXA抑制剂的浓度在凝血活酶试剂之间变化2.6至8倍。FXa抑制剂对PT比率的影响的等级顺序在促凝血酶原激酶试剂之间变化。转换为INR增加了变异性。不同的抗Xa测定显示每种FXa抑制剂的不同动态范围;然而，它们的排序是一致的。对于阿哌沙班，
Apixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases. Although routine monitoring will not be required, in certain situations assessment of drug level may be helpful.This study evaluated the suitability of commercially available prothrombin time/international normalised ratio (PT/INR) and anti-FXa activity assays to measure FXa inhibitors in plasma. Twelve PT (ISI 0.89-1.88) and three anti-Xa assays were evaluated in vitro using human plasma spiked with four FXa inhibitors (0-2,000 ng/ml). Assay variability and correlation with drug plasma exposure were evaluated in patients with venous thromboembolism (VTE) treated with apixaban. All FXa inhibitors prolonged PT; however, assay sensitivity was dependent on thromboplastin reagents used and FXa inhibitors tested. To achieve a doubling of PT, the concentration of each FXa inhibitor varied 2.6- to 8-fold between thromboplastin reagents. The rank order of a FXa inhibitor's effect on PT ratio varied across thromboplastin reagents. Conversion to INR increased variability. Different anti-Xa assays showed different dynamic ranges for each FXa inhibitor; however, their rank order was consistent. For apixaban, the dynamic range of