From the Laboratoire d'Hématologie.
Service de Chirurgie Thoracique et Cardio-Vasculaire, Centre Hospitalier Universitaire de Nantes, Nantes, France.
Anesth Analg. 2021 Mar 1;132(3):707-716. doi: 10.1213/ANE.0000000000005114.
Despite their usefulness in perioperative and acute care settings, factor-Xa inhibitor-specific assays are scarcely available, contrary to heparin anti-Xa assay. We assessed whether the heparin anti-Xa assay can (1) be used as a screening test to rule out apixaban, rivaroxaban, fondaparinux, and danaparoid levels that contraindicate invasive procedures according to current guidelines (>30 ng·mL-1, >30 ng·mL-1, >0.1 µg·mL-1, and >0.1 IU·mL-1, respectively), (2) quantify the anticoagulant level if found significant, that is, if it exceeded the abovementioned threshold.
In the derivation cohort then in the validation cohort, via receiver operating characteristics (ROC) curve analysis, we evaluated the ability of heparin anti-Xa assay to detect levels of factor-Xa inhibitors above or below the abovementioned safety thresholds recommended for an invasive procedure (screening test). Among samples with relevant levels of factor-Xa inhibitor, we determined the conversion factor linking the measured level and heparin anti-Xa activity in a derivation cohort. In a validation cohort, the estimated level of each factor-Xa inhibitor was thus inferred from heparin anti-Xa activity. The agreement between measured and estimated levels of factor-Xa inhibitors was assessed.
Among 989 (355 patients) and 756 blood samples (420 patients) in the derivation and validation cohort, there was a strong linear relationship between heparin anti-Xa activities and factor-Xa inhibitors measured level (r = 0.99 [95% confidence interval {CI}, 0.99-0.99]). In the derivation cohort, heparin anti-Xa activity ≤0.2, ≤0.3, <0.1, <0.1 IU·mL-1 reliably ruled out a relevant level of apixaban, rivaroxaban, fondaparinux, and danaparoid, respectively (area under the ROC curve ≥0.99). In the validation cohort, these cutoffs yielded excellent classification accuracy (≥96%). If this screening test indicated relevant level of factor-Xa inhibitor, estimated and measured levels closely agreed (Lin's correlation coefficient close to its maximal value: 95% CI, 0.99-0.99). More than 96% of the estimated levels fell into the predefined range of acceptability (ie, 80%-120% of the measured level).
A unique simple test already widely used to assay heparin was also useful for quantifying these 4 other anticoagulants. Both clinical and economic impacts of these findings should be assessed in a specific study.
尽管在围手术期和急性护理环境中非常有用，但与肝素抗 Xa 测定法相反，因子 Xa 抑制剂的特异性测定法几乎不可用。我们评估了肝素抗 Xa 测定法是否可以：(1) 用作筛选试验，根据当前指南排除有创程序禁忌的阿哌沙班、利伐沙班、磺达肝素和达那肝素水平（分别>30ng·mL-1、>30ng·mL-1、>0.1μg·mL-1 和>0.1IU·mL-1)；(2) 如果发现有意义，即如果超过上述阈值，则定量抗凝剂水平。
通过接收者操作特征 (ROC) 曲线分析，我们在推导队列中然后在验证队列中评估了肝素抗 Xa 测定法检测因子 Xa 抑制剂水平是否高于或低于推荐用于有创程序的上述安全阈值的能力（筛选试验）。在具有相关因子 Xa 抑制剂水平的样本中，我们在推导队列中确定了将测量水平与肝素抗 Xa 活性联系起来的换算系数。在验证队列中，因此可以根据肝素抗 Xa 活性推断出每个因子 Xa 抑制剂的估计水平。评估了因子 Xa 抑制剂的测量和估计水平之间的一致性。
在推导队列和验证队列中的 989（355 例）和 756 份（420 例）血液样本中，肝素抗 Xa 活性与因子 Xa 抑制剂的测量水平之间存在很强的线性关系（r = 0.99[95%置信区间{CI}，0.99-0.99]）。在推导队列中，肝素抗 Xa 活性≤0.2、≤0.3、<0.1、<0.1IU·mL-1 分别可靠地排除了阿哌沙班、利伐沙班、磺达肝素和达那肝素的相关水平（ROC 曲线下面积≥0.99）。在验证队列中，这些截止值产生了出色的分类准确性（≥96%）。如果该筛选试验表明存在相关水平的因子 Xa 抑制剂，则估计和测量水平非常吻合（Lin 的相关系数接近最大值：95%CI，0.99-0.99）。超过 96%的估计水平落入可接受的预定范围（即，80%-120%的测量水平）。
一种已经广泛用于肝素测定的独特简单测试也可用于定量测定这 4 种其他抗凝剂。应在专门的研究中评估这些发现的临床和经济影响。
