除D-二聚体检测外，C反应蛋白、降钙素原、凝血酶-抗凝血酶复合物及凝血因子VIII在基层医疗患者静脉血栓栓塞症排除诊断中的性能评估

Performance of C-Reactive Protein, Procalcitonin, TAT Complex, and Factor VIII in Addition to D-Dimer in the Exclusion of Venous Thromboembolism in Primary Care Patients.

作者信息

Heerink Jorn S, Gemen Eugenie, Oudega Ruud, Geersing Geert-Jan, Hopstaken Rogier, Kusters Ron

机构信息

Department of Clinical Chemistry and Haematology, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.

Department of Health Technology and Services Research, Technical Medical Centre, University of Twente, Enschede, the Netherlands.

出版信息

J Appl Lab Med. 2022 Mar 2;7(2):444-455. doi: 10.1093/jalm/jfab094.

DOI:10.1093/jalm/jfab094

PMID:34597379

Abstract

BACKGROUND

In primary care, D-dimer-combined with a clinical assessment-is recommended for ruling-out venous thromboembolism (VTE). However, D-dimer testing frequently yields false-positive results, notably in the elderly, and the search for novel biomarkers thus continues. We assessed the added diagnostic value of 4 promising laboratory tests.

METHODS

Plasma samples from 256 primary care patients suspected of VTE were collected. We explored added value (beyond D-dimer) of C-reactive protein (CRP), procalcitonin (PCT), thrombin-antithrombin III complex (TAT-c), and factor VIII (FVIII). Diagnostic performance of these biomarkers was assessed univariably and by estimating their area under the receiver operating curve (AUC). Added diagnostic potential beyond D-dimer testing was assessed using multivariable logistic regression.

RESULTS

Plasma samples of 237 VTE-suspected patients were available for analysis-36 patients (25%) confirmed deep vein thrombosis, 11 patients (12%) pulmonary embolism. Apart from D-dimer, only CRP, and FVIII levels appeared to be higher in patients with VTE compared to patients without VTE. The AUCs for these 3 markers were 0.76 (95% CI: 0.69-0.84) and 0.75 (95% CI: 0.68-0.83), respectively, whereas the AUC for D-dimer was 0.90 (95% CI: 0.86-0.94). Combining these biomarkers in a multivariable logistic model with D-dimer did not improve these AUCs meaningfully.

CONCLUSIONS

In our dataset, we were unable to demonstrate any added diagnostic performance beyond D-dimer testing of novel biomarkers in patients suspected of VTE in primary care. As such, D-dimer testing appears to remain the best choice in the exclusion of clinically suspected VTE in this setting.

TRIAL REGISTRATION

Netherlands Trial Register NL5974. (METC protocol number: 16-356/M; NL56475.041.16.).

摘要

背景

在初级医疗保健中，推荐使用D - 二聚体结合临床评估来排除静脉血栓栓塞症（VTE）。然而，D - 二聚体检测经常产生假阳性结果，尤其是在老年人中，因此对新型生物标志物的探索仍在继续。我们评估了4种有前景的实验室检测的附加诊断价值。

方法

收集了256例疑似VTE的初级医疗保健患者的血浆样本。我们探讨了C反应蛋白（CRP）、降钙素原（PCT）、凝血酶 - 抗凝血酶III复合物（TAT - c）和因子VIII（FVIII）超出D - 二聚体的附加价值。对这些生物标志物的诊断性能进行了单变量评估，并通过估计其受试者工作特征曲线下面积（AUC）进行评估。使用多变量逻辑回归评估超出D - 二聚体检测的附加诊断潜力。

结果

237例疑似VTE患者的血浆样本可供分析，36例患者（25%）确诊为深静脉血栓形成，11例患者（12%）确诊为肺栓塞。与无VTE的患者相比，除D - 二聚体外，只有CRP和FVIII水平在VTE患者中似乎更高。这3种标志物的AUC分别为0.76（95%CI：0.69 - 0.84）和0.75（95%CI：0.68 - 0.83），而D - 二聚体的AUC为0.90（95%CI：0.86 - 0.94）。在多变量逻辑模型中将这些生物标志物与D - 二聚体结合并没有显著提高这些AUC。