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狼疮抗凝物检测的优化:检测样本是否应始终与正常血浆混合?

Optimisation of lupus anticoagulant tests: should test samples always be mixed with normal plasma?

作者信息

Pennings Maarten T T, De Groot Philip G, Meijers Joost C M, Huisman Albert, Derksen Ronald H W M, Urbanus Rolf T

机构信息

Rolf T. Urbanus, PhD, Dept. Clinical Chemistry and Haematology, University Medical Centre Utrecht, Heidelberglaan 100, room G03.550, 3584 CX Utrecht, the Netherlands.

出版信息

Thromb Haemost. 2014 Oct;112(4):736-42. doi: 10.1160/TH14-02-0122. Epub 2014 Jul 10.

DOI:10.1160/TH14-02-0122
PMID:25008787
Abstract

Coagulation factor deficiencies are thought to interfere with the detection of the phospholipid-dependent coagulation inhibitor known as lupus anticoagulant (LA). Treatment with vitamin K antagonists (VKA) in particular, is thought to preclude accurate LA assessment. For this reason, the procedure to detect LA includes a mixing test, in which coagulation factor deficiencies are corrected by mixing samples with an equal volume of normal plasma. Despite these mixing tests, interpretation of LA test results is considered difficult in patients receiving high intensity VKA treatment. As a result, VKA treatment is often temporarily discontinued to allow LA assessment. However, whether coagulation factor deficiencies influence LA test results is unclear. We found that neither deficiency of a single coagulation factor, nor a functional coagulation factor deficiency due to high intensity VKA treatment, resulted in false positive dRVVT- or APTT-based (silica clotting time; SCT) LA test results. LA was readily detected in unmixed samples from VKA-treated LA-positive patients with both dRVVT and SCT reagents. VKA treatment caused an underestimation of the strength of the LA with SCT reagents, but did not lead to misclassification of LA status. Although mixing with normal plasma during both screen and confirm tests allowed more accurate assessment of the strength of the LA with SCT reagents in samples with an international normalised >2.5, the mixing procedure itself lead to misclassification of LA in weakly positive samples from patients not treated with VKA. Based on these findings, we conclude that mixing studies are not necessary during LA-assessment.

摘要

凝血因子缺乏被认为会干扰对称为狼疮抗凝物(LA)的磷脂依赖性凝血抑制剂的检测。特别是维生素K拮抗剂(VKA)治疗,被认为会妨碍LA的准确评估。因此,检测LA的程序包括一项混合试验,即通过将样本与等量的正常血浆混合来纠正凝血因子缺乏。尽管有这些混合试验,但在接受高强度VKA治疗的患者中,LA检测结果的解读仍被认为很困难。因此,VKA治疗常常会暂时中断以进行LA评估。然而,凝血因子缺乏是否会影响LA检测结果尚不清楚。我们发现,单一凝血因子缺乏,以及高强度VKA治疗导致的功能性凝血因子缺乏,均不会导致基于dRVVT或APTT(硅土凝血时间;SCT)的LA检测结果出现假阳性。使用dRVVT和SCT试剂均可在VKA治疗的LA阳性患者的未混合样本中轻松检测到LA。VKA治疗会导致使用SCT试剂时对LA强度的低估,但不会导致LA状态的错误分类。尽管在筛查和确证试验中与正常血浆混合可使国际标准化比值>2.5的样本中使用SCT试剂更准确地评估LA强度,但混合程序本身会导致未接受VKA治疗患者的弱阳性样本中LA出现错误分类。基于这些发现,我们得出结论,在LA评估过程中无需进行混合研究。

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