Department of Laboratory Haematology, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia; Sydney Centres for Thrombosis and Haemostasis, Sydney, NSW, Australia.
Department of Laboratory Haematology, Institute of Clinical Pathology and Medical Research, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia.
Pathology. 2019 Apr;51(3):292-300. doi: 10.1016/j.pathol.2018.11.008. Epub 2019 Jan 18.
We and others have previously highlighted the potential problems with testing of lupus anticoagulants (LA) in patients on anticoagulant therapy, including most recently as related to the direct oral anticoagulants (DOACs). Thus, current DOACs in use (e.g., dabigatran, a direct thrombin inhibitor, and apixaban and rivaroxaban, both direct Xa inhibitors), affect a wide variety of coagulation assays, including those used in LA investigation. The Russell viper venom time (RVVT) assay in particular, key to the investigation of LA, is highly sensitive to DOACs. LA is a marker of thrombophilia, and patients who have had a thrombosis may be placed on a DOAC. Thus, there is a high likelihood that LA testing will be requested on patients whilst they are on DOACs. In the current report, we have assessed data from our facility for the past two and a half years for all LA tests performed by RVVT testing, and have evaluated this data with respect to patient anticoagulant status. In total, there were 7170 test requests for RVVT associated testing during the period of data capture. Most LA-RVVT screen results (5008; ∼70%) were within normal limits, thereby excluding LA by RVVT method in most of the patient cohort. All DOACs led to a prolongation in both RVVT screen and confirm assays. However, rivaroxaban affected the screen more than the confirm, leading to higher RVVT ratios, whereas apixaban affected the confirm more than the screen, leading to lower RVVT ratios. LA testing in the presence of DOACs also led to lower intra-patient consistency in LA test results. We conclude that ex-vivo data appears to confirm the potential for false positive (with rivaroxaban) and potential for false negative (with apixaban) identification of LA in patients on DOAC treatment. We also make some recommendations in regards to such testing.
我们和其他人之前已经强调了在接受抗凝治疗的患者中检测狼疮抗凝物 (LA) 时可能存在的问题，包括最近与直接口服抗凝剂 (DOAC) 相关的问题。因此，目前正在使用的直接口服抗凝剂（例如，达比加群，一种直接凝血酶抑制剂，以及阿哌沙班和利伐沙班，均为直接 Xa 抑制剂）会影响多种凝血检测，包括用于 LA 检测的检测。特别是对于 LA 检测至关重要的 Russell 蝰蛇毒时间 (RVVT) 检测，对 DOAC 非常敏感。LA 是血栓形成倾向的标志物，已经发生血栓的患者可能会被放置在 DOAC 上。因此，在患者使用 DOAC 时，很可能会要求进行 LA 检测。在当前报告中，我们评估了过去两年半来我们机构所有通过 RVVT 检测进行的 LA 检测的数据，并根据患者的抗凝状态评估了这些数据。在数据采集期间，共有 7170 个 RVVT 相关检测的 LA 检测请求。大多数 LA-RVVT 筛查结果（5008；约 70%）均在正常范围内，从而通过 RVVT 方法排除了大多数患者队列中的 LA。所有 DOAC 均导致 RVVT 筛查和确认检测均延长。然而，利伐沙班对筛查的影响大于确认，导致 RVVT 比值更高，而阿哌沙班对确认的影响大于筛查，导致 RVVT 比值更低。在存在 DOAC 的情况下进行 LA 检测也导致 LA 检测结果在患者内的一致性降低。我们得出结论，体外数据似乎证实了在接受 DOAC 治疗的患者中，LA 的假阳性（利伐沙班）和假阴性（阿哌沙班）的可能性。我们还就此类检测提出了一些建议。
