Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium.
Clinical Department of Laboratory Medicine, University Hospitals of Leuven, Leuven, Belgium.
Int J Lab Hematol. 2018 Aug;40(4):442-447. doi: 10.1111/ijlh.12807. Epub 2018 Mar 24.
The direct thrombin inhibitor dabigatran interferes with thrombophilia screening and with the diagnosis of hemostasis disorders that develop during treatment with the anticoagulant. In vitro addition of idarucizumab, a humanized antibody fragment that binds dabigatran, to plasma samples containing dabigatran fully neutralizes the drug. This study was carried out to determine whether binding of dabigatran on selected insoluble commercial adsorbent material, DOAC-STOP , was as efficient as idarucizumab to neutralize the anticoagulant activity of the drug in vitro.
Coagulation assays sensitive to dabigatran were carried out with patient and control plasma samples spiked with dabigatran and supplemented with idarucizumab or incubated with adsorbent material.
In samples containing upto 10 000 ng/mL dabigatran, the adsorption procedure was at least as efficient as the addition of idarucizumab to neutralize the activity of the anticoagulant drug. Neither the adsorption procedure nor the addition of idarucizumab did impair routine coagulation assays carried out with plasma devoid of dabigatran, such as the activated partial thromboplastin time, prothrombin time, fibrinogen Clauss, and the thrombophilia screening assays used to detect antiphospholipid antibodies or activated protein C resistance. In addition, the adsorption procedure did not interfere with the detection of lupus anticoagulant samples.
Adsorption of dabigatran in plasma samples containing the drug neutralizes its activity as efficiently as the addition of idarucizumab. This method allows the evaluation of thrombophilia markers without interruption of anticoagulation therapy or the detection of hemostasis disorders in patients treated with the drug.
直接凝血酶抑制剂达比加群会干扰血栓形成倾向的筛查，以及干扰抗凝治疗期间发生的止血紊乱的诊断。在含有达比加群的血浆样本中加入一种与人源化抗体片段idarucizumab 能完全中和该药。本研究旨在确定idarucizumab 与选定的不溶性商业吸附剂材料 DOAC-STOP 结合是否能像 idarucizumab 一样有效地中和药物的体外抗凝活性。
用添加了达比加群的患者和对照血浆样本进行对达比加群敏感的凝血检测，并补充idarucizumab 或孵育吸附剂材料。
在含有高达 10 000 ng/ml 达比加群的样本中，吸附程序至少与添加idarucizumab一样能有效地中和抗凝药物的活性。吸附程序或添加idarucizumab 均不会损害用不含达比加群的血浆进行的常规凝血检测，如激活部分凝血活酶时间、凝血酶原时间、纤维蛋白原 Clauss 以及用于检测抗磷脂抗体或活化蛋白 C 抵抗的血栓形成倾向筛查检测。此外，该吸附程序不干扰狼疮抗凝剂样本的检测。
在含有药物的血浆样本中吸附达比加群能像添加idarucizumab 一样有效地中和其活性。该方法允许在不中断抗凝治疗的情况下评估血栓形成标志物，或在接受药物治疗的患者中检测止血紊乱。
