Abstract
排除肺栓塞的D-二聚体阈值不应基于“最佳”Youden指数
SARS-CoV-2的流行给肺栓塞的诊断提出了新的挑战[1]。第atients with COVID-19 are at increased risk of developing venous thromboembolism, but symptoms of COVID-19 and PE may overlap, which makes it difficult to identify those with a higher likelihood of PE. Simple and minimally-invasive diagnostic algorithms that can safely rule-out PE in patients with COVID-19 are urgently needed. Therefore, we read with interest the recent paper by Mouhat and colleagues in theEuropean Respiratory Journal[2]。
在他们的研究中,作者回顾性评估了162例严重COVID-19住院患者中与PE相关的因素,这些患者接受了ct肺动脉造影(CTPA)作为PE的参考标准。他们报道有两个变量与PE显著相关:未接受抗凝治疗和D-二聚体检测。作者报告说,他们“确定了D-二聚体的临界值为2590 ng·mL−1最好地预测PE的发生。他们提出“我们的数据支持更广泛的PE筛查策略,对临床症状严重且D-二聚体水平>2590 ng·mL的COVID-19患者进行CTPA−1”, and that “particular attention should be paid to search for potential PE in patients [..] with a D-dimer level above 2590 ng·mL−1”. 然而,我们认为选择D-二聚体阈值的基本原理与临床无关,并且不能安全地应用于COVID-19患者。
D-二聚体检测不够准确,不能单独用于PE的诊断[三]. 因此,诸如Wells法则和YEARS准则等诊断算法已经被开发出来,其中D-二聚体被用作分类测试[4,5]. 低D-二聚体(通常阈值为500或1000 ng·mL)的患者−1在没有CTPA的情况下可以安全地排除PE。相反,在D-二聚体高于阈值的患者中,需要进行后续CTPA。在这些算法中,D-二聚体阈值的选择基于这样一个事实,即它们对应于接近100%的阴性预测值(NPV),从而确保无需进一步测试就可以安全地排除PE[6]。
Whether similar D-dimer thresholds can be applied in COVID-19 patients suspected of PE is unknown, because COVID-19 triggers a hyperinflammatory state with endothelial activation and high D-dimer levels [7]。在他们的文章中,Mouhat和同事提出了2590 ng·ml的阈值−1[2]。T型his threshold was not selected to obtain an NPV close to 100%, but it was based on the highest “Youden's index”. This works as follows: within the study population, for every D-dimer threshold, a corresponding sensitivity and specificity for diagnosing PE is calculated. If the D-dimer threshold is set at 0 ng·mL−1,每个患者被认为是“阳性”,暗示敏感性为100%,特异性为0%。当增加阈值时,更多的患者将具有“负”D-二聚体,导致敏感性降低和特异性增加。每个可能的D-二聚体阈值对应于一对灵敏度和特异性,并且这些对可以绘制到接收器操作特性(ROC)曲线中(图5中的Mouhat和同事纸)。提供最高yeden索引的阈值是最大化[敏感性+特异性]。它也是最大化Logistic回归建模中的差距的阈值。
在大多数情况下,根据最高的Youden指数选择生物标志物的阳性阈值可能具有统计学意义,但与临床无关。这种数据驱动的“最佳”阈值选择不仅可能导致偏差的准确度估计和较差的再现性[8]但是,它通常也导致敏感性和特异性参数,其分别太低,分别,排除或规则 - 在目标条件下,具有足够的确定性。在Mouhat和同事的研究中,所提出的D-二聚体阈值为2590 ng·ml−1leads to a sensitivity of 83.3% (95%CI 68.6–93.0) and a specificity of 83.8% (95%CI 73.8–91.1), corresponding to a positive predictive value (PPV) of 72.9% (95%CI 61.7–81.8) and an NPV of 90.5% (95%CI 82.9–95.0). This implies that using this threshold in clinical practice would result in missing 17% of PE, which is unacceptable.
We believe that Mouhat and colleagues should have provided an ROC table, showing sensitivity and specificity at multiple D-dimer thresholds, so that a threshold corresponding to an NPV close to 100% could have been identified, as this is clinically much more meaningful. We strongly urge physicians not to apply the threshold proposed by the authors in clinical practice, as this is likely to result in a considerable proportion of PE being missed. We also encourage researchers evaluating the diagnostic accuracy of markers such as D-dimer to select thresholds based on minimally acceptable targets of accuracy estimates rather than on maximising the Youden's index [9]。T型here are considerable concerns regarding the quality of diagnostic accuracy and prediction model studies in the COVID-19 literature [10,11]。至关重要的是,研究人员通过应用此类研究的可用方法和报告指南来努力改善这一点[12,13]。
脚注
利益冲突:科雷瓦尔博士没有什么要披露的。
C级onflict of interest: Dr. van Es has nothing to disclose.
- 收到November 20, 2020.
- 认可的2020年12月14日。
- 版权所有©ERS 2020
T型his article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.