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普通肝素、依诺肝素和达那肝素对狼疮抗凝物检测的影响:活性炭能否消除假阳性结果?

The effect of unfractionated heparin, enoxaparin, and danaparoid on lupus anticoagulant testing: Can activated carbon eliminate false-positive results?

作者信息

De Kesel Pieter M M, Devreese Katrien M J

机构信息

Coagulation Laboratory Department of Laboratory Medicine Ghent University Hospital Ghent Belgium.

出版信息

Res Pract Thromb Haemost. 2019 Dec 10;4(1):161-168. doi: 10.1002/rth2.12264. eCollection 2020 Jan.

Abstract

BACKGROUND

Heparins and heparinoids interfere with functional clotting assays used for lupus anticoagulant (LAC) detection. However, current guidelines for LAC testing do not provide clear guidance on this matter.

OBJECTIVES

We aimed to assess to effect of unfractionated heparin (UFH), enoxaparin, and danaparoid on LAC assays over broad anti-Xa activity ranges and to evaluate whether activated carbon (AC) is able to neutralize these effects.

METHODS

UFH (0.1-3.0 IU/mL), enoxaparin (0.2-2.9 IU/mL), and danaparoid (0.6-2.2 IU/mL) were spiked to normal pooled plasma. AC was added at multiple activity levels. Anti-Xa assays and LAC tests were performed on all samples using Stago analyzers and reagents.

RESULTS

Abnormal activated partial thromboplastin time (APTT) screening and mixing tests were obtained at the lowest levels for all compounds. Abnormal APTT confirmation tests were seen from 2.5 and 1.9 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dilute Russell's viper venom test (dRVVT) screening tests were obtained from 1.6, 1.4, and 1.1 anti-Xa IU/mL for UFH, enoxaparin, and danaparoid, respectively. Mixing tests were abnormal from 2.5 and 1.3 anti-Xa IU/mL for enoxaparin and danaparoid, respectively. Abnormal dRVVT confirmation results were seen for danaparoid only from 1.9 anti-Xa IU/mL. AC was unable to neutralize anti-Xa activity in plasma and overcome the effect of the tested anticoagulants on LAC assays but may cause prolongation of APTT clotting times.

CONCLUSIONS

UFH, enoxaparin, and danaparoid clearly affected LA tests; however, false-positive LAC conclusions were obtained at supratherapeutic enoxaparin and danaparoid levels only. AC may prolong APTT screen clotting times, requiring 3-step testing to avoid potential misdiagnosis of LAC.

摘要

背景

肝素和类肝素会干扰用于检测狼疮抗凝物(LAC)的功能性凝血试验。然而,目前关于LAC检测的指南并未就此问题提供明确指导。

目的

我们旨在评估普通肝素(UFH)、依诺肝素和达那肝素在较宽的抗Xa活性范围内对LAC检测的影响,并评估活性炭(AC)是否能够中和这些影响。

方法

将UFH(0.1 - 3.0 IU/mL)、依诺肝素(0.2 - 2.9 IU/mL)和达那肝素(0.6 - 2.2 IU/mL)加入正常混合血浆中。在多个活性水平下添加AC。使用Stago分析仪和试剂对所有样本进行抗Xa检测和LAC检测。

结果

所有化合物在最低水平时均获得异常的活化部分凝血活酶时间(APTT)筛查和混合试验结果。依诺肝素和达那肝素分别在抗Xa活性为2.5和1.9 IU/mL时出现异常的APTT确证试验结果。UFH、依诺肝素和达那肝素分别在抗Xa活性为1.6、1.4和1.1 IU/mL时获得异常的稀释蝰蛇毒时间(dRVVT)筛查试验结果。依诺肝素和达那肝素分别在抗Xa活性为2.5和1.3 IU/mL时混合试验结果异常。仅达那肝素在抗Xa活性为1.9 IU/mL时出现异常的dRVVT确证结果。AC无法中和血浆中的抗Xa活性,也无法克服受试抗凝剂对LAC检测的影响,但可能会导致APTT凝血时间延长。

结论

UFH、依诺肝素和达那肝素明显影响LAC检测;然而,仅在依诺肝素和达那肝素超治疗水平时会得出假阳性的LAC结论。AC可能会延长APTT筛查凝血时间,需要三步检测以避免LAC的潜在误诊。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43b/6971310/5d89f60d149f/RTH2-4-161-g001.jpg

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