Ofek Fanny, Bar Chaim Samuel, Kronenfeld Nirit, Ziv-Baran Tomer, Berkovitch Matitiahu
Pharmacy Department, Assaf Harofeh Medical Center, Zerifin, Israel.
Emergency Department, Assaf Harofeh Medical Center, Zerifin, Israel.
Clin Ther. 2017 May;39(5):1003-1010. doi: 10.1016/j.clinthera.2017.04.007. Epub 2017 May 2.
Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself.
The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions.
No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001).
Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.
利伐沙班或阿哌沙班等直接凝血因子Xa抑制剂可能会延长凝血酶原时间（PT）并提高国际标准化比值（INR）。然而，这些检测对于评估这些药物的抗凝效果并不可靠。在治疗药物浓度下，PT测定的敏感性相对较弱，并且会因所使用的试剂而有显著差异。将PT转换为INR甚至可能增加变异性。我们进行了一项回顾性横断面研究，旨在评估接受利伐沙班或阿哌沙班作为家庭用药一部分的住院患者中INR升高的患病率和程度，并找出除药物本身外是否有其他现有因素可使INR升高。
从218例住院患者的病历中收集的数据包括入院时的PT和INR、患者特征、实验室检查结果、定期使用的其他药物以及并存的临床情况。
在我们的研究中，未发现INR升高与所检查参数之间存在统计学上的显著关联。两个药物组的INR均显著升高（P < 0.001），利伐沙班组84.2%的患者和阿哌沙班组78.3%的患者INR水平高于正常范围的上限。此外，利伐沙班组的INR显著高于阿哌沙班组（P < 0.001）。
所审查的两种药物均显著提高了INR。此外，利伐沙班使INR升高的幅度明显大于阿哌沙班，而且显然除药物本身外没有其他因素影响INR。需要更大规模的前瞻性研究来证实和阐明这些结果的临床意义。
