Department of Laboratory Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW 2145, Australia.
Sydney Centres for Thrombosis and Haemostasis, Westmead Hospital, Westmead, NSW, Australia.
Clin Chem Lab Med. 2020 Jul 28;58(8):1322-1331. doi: 10.1515/cclm-2019-1160.
Background Investigation of hemostasis is problematic when patients are on anticoagulant therapy. Rivaroxaban especially causes substantial interference, extending many clot-based tests, thereby leading to false positive or negative events. In particular, rivaroxaban affects some assays for activated protein C resistance (APCR). Methods We assessed, in an international setting, cross laboratory (n = 31) testing using four samples to evaluate rivaroxaban induced interference in APCR testing, and whether this interference could be neutralised. The samples comprised: (A) pool of normal plasma (APCR-negative control); (B) this normal pool spiked with rivaroxaban (200 ng/mL) to create rivaroxaban-induced interference (potential 'false' positive APCR event sample); (C) the rivaroxaban sample subsequently treated with a commercial direct oral anticoagulant 'DOAC-neutraliser' (DOAC Stop), or (D) treated with andexanet alfa (200 μg/mL). Testing was performed blind to sample type. Results The rivaroxaban-spiked sample generated false positive APCR results for some, but unexpectedly not most APCR-tests. The sample treated with DOAC Stop evidenced a correction in the rivaroxaban-affected APCR assays, and did not otherwise adversely affect the rivaroxaban 'unaffected' APCR assays. The andexanet alfa-treated sample did not evidence correction of the false positive APCR, and instead unexpectedly exacerbated false positive APCR status with many tests. Conclusions DOAC Stop was able to neutralise any APCR interference induced by rivaroxaban. In contrast, andexanet alfa did not negate such interference, and instead unexpectedly created more false-positive APCR events.
背景调查 在抗凝治疗的患者中，止血的背景调查存在问题。利伐沙班尤其会造成大量干扰，延长许多基于凝结块的检测，从而导致假阳性或假阴性结果。特别是，利伐沙班会影响一些激活蛋白 C 抵抗（APCR）的检测。
方法 我们在国际范围内评估了使用四个样本进行的实验室间检测，以评估利伐沙班诱导的 APCR 检测干扰，以及这种干扰是否可以被中和。样本包括：（A）正常血浆混合液（APCR 阴性对照）；（B）正常混合液中加入利伐沙班（200ng/mL）以产生利伐沙班诱导的干扰（潜在的“假”阳性 APCR 事件样本）；（C）用商业直接口服抗凝剂（DOAC）“中和剂”（DOAC Stop）处理的利伐沙班样本，或（D）用 andexanet alfa（200μg/mL）处理的样本。检测在不知道样本类型的情况下进行。
结果 利伐沙班加标样本对一些但不是大多数 APCR 检测产生了假阳性 APCR 结果。用 DOAC Stop 处理的样本显示出对利伐沙班影响的 APCR 检测的纠正，而不会对未受利伐沙班影响的 APCR 检测产生不利影响。用 andexanet alfa 处理的样本没有纠正假阳性 APCR，而是用许多测试意外地加剧了假阳性 APCR 状态。
结论 DOAC Stop 能够中和利伐沙班引起的任何 APCR 干扰。相比之下，andexanet alfa 并没有消除这种干扰，而是出人意料地产生了更多的假阳性 APCR 事件。
