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, Westmead, NSW, Australia.
Haemophilia. 2020 Mar;26(2):354-362. doi: 10.1111/hae.13930. Epub 2020 Jan 21.
Investigation of factors (F) VIII and IX is common, with testing important for diagnosis or exclusion of haemophilia A or B, associated acquired conditions and factor inhibitors. Rivaroxaban, a common direct anti-Xa agent, causes significant interference in clotting assays, including substantial false reduction of factor levels.
To assess whether rivaroxaban-induced interference of FVIII and FIX testing could be neutralized.
An international, cross-laboratory exercise for FVIII (n = 84) and FIX (n = 74), using four samples: (A) pool of normal plasma; (B) pool spiked with rivaroxaban (200 ng/mL); (C) rivaroxaban sample subsequently treated with 'DOAC Stop' and; (D) rivaroxaban sample treated with andexanet alfa (200 μg/mL). Testing performed blind to sample type.
All laboratories reported normal FIX and 94% reported normal FVIII in the pool sample. Instead, 55% and 95%, respectively, reported abnormal FIX and FVIII levels for the rivaroxaban sample. DOAC Stop treatment evidenced a correction in most laboratories (100% reported normal FIX and 86% normal FVIII). Andexanet alfa provided intermediate results, with many laboratories still reporting abnormal results (59% for FVIII, 18% for FIX). We also identified reagent-specific issues.
As expected, rivaroxaban caused false low values of FVIII and FIX. This might lead to increased testing to identify the cause of low factor levels and potentially lead to false identification of (mild) haemophilia A or B if unrecognized by clinicians/laboratories. DOAC Stop effectively neutralized the rivaroxaban effect, but andexanet alfa less so, with reagent-related effects evident, and thus, false low values sometimes persisted.
VIII 因子和 IX 因子的检测很常见，对于诊断或排除血友病 A 或 B、相关获得性疾病和因子抑制剂的检测非常重要。利伐沙班是一种常见的直接抗-Xa 药物，会对凝血检测造成显著干扰，包括因子水平的明显假性降低。
评估利伐沙班是否会导致 FVIII 和 FIX 检测的干扰，以及这种干扰是否可以被中和。
本研究为一项国际跨实验室的 FVIII（n=84）和 FIX（n=74）检测研究，使用了四个样本：（A）正常血浆混合池；（B）混合了利伐沙班（200ng/mL）的混合池；（C）随后用“DOAC Stop”处理的利伐沙班组；（D）用 andexanet alfa（200μg/mL）处理的利伐沙班组。检测是在不了解样本类型的情况下进行的。
所有实验室均报告正常的 FIX 和 94%的正常 FVIII 在混合池样本中。相反，55%和 95%的实验室分别报告了利伐沙班组的异常 FIX 和 FVIII 水平。DOAC Stop 处理后，大多数实验室（100%报告正常 FIX，86%报告正常 FVIII）得到纠正。andexanet alfa 提供了中间结果，许多实验室仍报告异常结果（59%的 FVIII，18%的 FIX）。我们还发现了试剂特异性问题。
正如预期的那样，利伐沙班导致了 FVIII 和 FIX 的假性低值。这可能会导致更多的检测来识别低因子水平的原因，并可能导致（轻度）血友病 A 或 B 的错误识别，如果临床医生/实验室没有识别出来的话。DOAC Stop 有效地中和了利伐沙班的作用，但 andexanet alfa 的效果则不那么明显，存在试剂相关的影响，因此，假性低值有时仍然存在。
