Department of CardioMetabolic Disease Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.
Am J Med. 2012 Apr;125(4):417-20. doi: 10.1016/j.amjmed.2011.10.017. Epub 2012 Feb 3.
Point-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue.
We compared INR levels in whole blood and plasma using a Hemochron Jr. Signature+ point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran.
Prothrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of-care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples.
INR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran.
即时凝血酶原时间（INR）检测设备常用于监测维生素 K 拮抗剂治疗患者的治疗情况并维持其抗凝血治疗水平。达比加群是一种新型口服、可逆的直接凝血酶抑制剂，已获批用于房颤患者的卒中预防，无需常规凝血监测。然而，一些病例报告显示，在使用 Hemochron 等即时凝血酶原时间检测设备治疗达比加群的患者中，检测到了假性升高的 INR 水平。本体外研究旨在验证这一问题。
我们使用 Hemochron Jr. Signature+即时凝血酶原时间检测设备（International Technidyne Corporation，Edison，NJ）和常规实验室监测，比较了健康志愿者血液样本的 INR 水平和血浆 INR 水平，这些血液样本中添加了不同浓度的达比加群。
与实验室测量相比，即时凝血酶原时间检测设备检测的凝血酶原时间和 INR 水平在整个血浆达比加群浓度范围（50-1400ng/mL）内升高了 2-4 倍。在患者中可能观察到的达比加群血浆浓度下（150mg 每日两次，60-275ng/mL），即时全血 INR 值从 1.7 升高至 4.0，而实验室凝血仪测量值为 1.1-1.5。在血浆样本中也观察到了类似的凝血酶原时间差异。
与实验室值相比，使用 Hemochron Jr.即时凝血酶原时间检测设备测量达比加群患者的 INR 水平显著升高。我们特别不鼓励使用这些设备，以及一般情况下使用 INR 来测量达比加群的抗凝效果。
