BACKGROUND AND PURPOSE In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated anti-Xa thresholds up to 50 ng/mL have been proposed. However, specific DOAC assays are not widely available contrarily to low-molecularweight heparin (LMWH) anti-Xa activity. We developed and validated a nomogram for predicting apixaban and rivaroxaban concentrations based on LMWH anti-Xa assay. METHODS Our prospective study included apixaban (n=325) and rivaroxaban (n=276) patients. On the same sample, we systematically measured specific DOAC concentration and LMWH anti-Xa activity, using STA®-Liquid-Anti-Xa (Stago) and specific DOAC- or LMWH-calibrators, respectively. The nomogram was built using quantifiable values for both assays on the derivation cohorts with a log-linear regression model. Model performances including sensitivity, specificity, and true positive rate for different thresholds were checked on the validation cohorts. RESULTS The models built from the derivation cohorts predicted that values <30 ng/mL and <50 ng/ mL DOAC thresholds corresponded to LMWH-anti-Xa values <0.10 IU/mL and <0.64 IU/mL for apixaban; <0.10 IU/mL and <0.71 IU/mL for rivaroxaban. The model accurately predicted apixaban/ rivaroxaban concentrations in the validation cohort. CONCLUSIONS This easy-to-use nomogram, developed with our reagent, allowed accurately predicting DOAC concentrations based on LMWH-anti-Xa results in emergency situations such as AIS when drug-specific assessments are not rapidly available. Using DOAC <50 ng/mL equivalent threshold, instead of the fixed LMWH <0.5 IU/mL one, would allow proposing thrombolysis to more patients.

中文翻译：

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从低分子肝素抗 Xa 值预测阿哌沙班或利伐沙班浓度的实用列线图：对急性缺血性中风患者的特殊兴趣。

背景和目的 在过去 48 小时内使用直接口服 Xa 因子抗凝剂 (DOAC) 的急性缺血性卒中 (AIS) 患者中，建议将固定的血浆肝素校准抗 Xa 活性 (0.5 IU/mL) 作为阈值低于该值的患者可能有资格进行溶栓和/或血栓切除术。此外，还提出了高达 50 ng/mL 的特定 DOAC 校准抗 Xa 阈值。然而，与低分子量肝素 (LMWH) 抗 Xa 活性相反，特定的 DOAC 检测方法并未广泛应用。我们开发并验证了基于 LMWH 抗 Xa 测定法预测阿哌沙班和利伐沙班浓度的列线图。方法 我们的前瞻性研究包括阿哌沙班 (n=325) 和利伐沙班 (n=276) 患者。在同一样本上，我们系统地测量了特定的 DOAC 浓度和 LMWH 抗 Xa 活性，分别使用 STA®-Liquid-Anti-Xa (Stago) 和特定的 DOAC 或 LMWH 校准器。列线图是使用对数线性回归模型的推导队列的两种测定的可量化值构建的。在验证队列中检查了不同阈值的模型性能，包括灵敏度、特异性和真阳性率。结果 根据推导队列建立的模型预测，对于阿哌沙班，<30 ng/mL 和 <50 ng/mL DOAC 阈值对应于 LMWH-anti-Xa 值 <0.10 IU/mL 和 <0.64 IU/mL；利伐沙班 <0.10 IU/mL 和 <0.71 IU/mL。该模型准确预测了验证队列中的阿哌沙班/利伐沙班浓度。结论 这种使用我们的试剂开发的易于使用的列线图，允许在紧急情况下根据 LMWH-anti-Xa 结果准确预测 DOAC 浓度，例如 AIS，当药物特异性评估无法快速获得时。使用 DOAC <50 ng/mL 等效阈值，而不是固定的 LMWH <0.5 IU/mL，将允许向更多患者提出溶栓建议。