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, Australia.
Western Australian Centre for Thrombosis and Haemostasis (WACTH), Murdoch University, Perth, WA, Australia.
Thromb Res. 2019 Aug;180:10-19. doi: 10.1016/j.thromres.2019.05.013. Epub 2019 May 24.
Lupus anticoagulant (LA) investigation in patients on anticoagulant therapy is problematic. Rivaroxaban in particular causes significant interference, prolonging both LA screening and confirmation tests, and falsely raising LA screen/confirm ratios, leading to potential false identification of LA. The Russell Viper Venom Time (RVVT) assay, key to the investigation of LA, is especially sensitive to rivaroxaban.
We assessed cross laboratory (n = 82) testing of four samples to investigate whether rivaroxaban induced interference in LA testing could be neutralised. Testing was performed blind to sample type. The samples comprised: (A) A pool of normal plasma (LA-negative control); (B) sample A spiked with rivaroxaban (200 ng/mL) to create rivaroxaban-induced interference (LA 'false' positive sample); (C) sample B subsequently treated with a commercial 'DOAC-neutraliser' (DOAC Stop); (D) sample B treated with andexanet alfa (200 μg/mL).
As expected, the rivaroxaban-spiked sample (B) caused prolongation of most LA-tests, and also generated a falsely prolonged RVVT screen/confirm ratio (median 1.37, compared to 0.97 for sample A). The sample (C) treated with DOAC Stop evidenced a correction in LA-test clotting times, as well as neutralising the false positive LA (median RVVT screen/confirm ratio of 0.99). Although the andexanet alfa treated sample (D) also yielded a low median RVVT screen/confirm ratio of 0.88, it did not fully correct LA-test clotting times. Consistent with test findings, all laboratories interpreted samples A and C as being LA-negative. For sample B (rivaroxaban), 45.3% identified this as LA positive, and 38.7% identified LA interference. Most (61.3%) also identified sample D as LA negative, with the remainder (38.7%) identifying LA interference.
DOAC Stop was able to neutralise the false LA activity induced by rivaroxaban, both in terms of clot-times and LA ratios. In contrast, whilst andexanet alfa negated the rivaroxaban-prolonged LA-ratio, it did not fully correct clot-times, leaving some residual LA interference, and requiring additional testing to investigate prolonged clotting times.
在接受抗凝治疗的患者中进行狼疮抗凝物（LA）检测存在问题。利伐沙班尤其会造成显著干扰，延长 LA 筛查和确认试验，并错误地提高 LA 筛查/确认比值，从而可能导致 LA 的假阳性识别。关键的 LA 检测 Russell 蝰蛇 venom time（RVVT）检测法尤其容易受到利伐沙班的影响。
我们评估了四个样本的实验室间检测，以研究利伐沙班诱导的 LA 检测干扰是否可以被中和。检测是在不了解样本类型的情况下进行的。样本包括：（A）正常血浆池（LA 阴性对照）；（B）用利伐沙班（200ng/mL）添加到样本 A 中以产生利伐沙班诱导的干扰（LA“假”阳性样本）；（C）随后用商业 DOAC 中和剂（DOAC Stop）处理样本 B；（D）用 andexanet alfa（200μg/mL）处理样本 B。
正如预期的那样，添加利伐沙班的样本（B）引起大多数 LA 试验的延长，并且还产生了错误延长的 RVVT 筛查/确认比值（中位数 1.37，而样本 A 为 0.97）。用 DOAC Stop 处理的样本（C）显示 LA 试验凝血时间得到纠正，并中和了假阳性 LA（中位数 RVVT 筛查/确认比值为 0.99）。尽管用 andexanet alfa 处理的样本（D）也产生了较低的中位数 RVVT 筛查/确认比值 0.88，但它并没有完全纠正 LA 试验凝血时间。与试验结果一致，所有实验室均将样本 A 和 C 判为 LA 阴性。对于样本 B（利伐沙班），45.3%的实验室将其鉴定为 LA 阳性，38.7%的实验室将其鉴定为 LA 干扰。大多数（61.3%）实验室也将样本 D 鉴定为 LA 阴性，其余（38.7%）实验室鉴定为 LA 干扰。
DOAC Stop 能够中和利伐沙班诱导的假 LA 活性，无论是在凝血时间还是 LA 比值方面。相比之下，虽然 andexanet alfa 消除了利伐沙班延长的 LA-比值，但它并没有完全纠正凝血时间，仍存在一些残留的 LA 干扰，需要进一步检测以研究延长的凝血时间。
