Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy.
Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.
Front Immunol. 2019 Mar 5;10:376. doi: 10.3389/fimmu.2019.00376. eCollection 2019.
Is it well-known that one of the major drawbacks of Lupus Anticoagulant (LA) test is their sensitivity to anticoagulant therapy, due to the coagulation based principle. In this study we aimed to assess the reproducibility of LA testing and to evaluate the performance of solid assay phosphatidylserine/prothrombin (aPS/PT) antibodies. We included 60 patients that fulfilled the following inclusion criteria: (I) diagnosis of thrombotic antiphospholipid syndrome (APS); (II) patients with thrombosis and (a) inconstant previous LA positivity and/or (b) positivity for antiphospholipid antibodies (aPL) at low-medium titers [defined as levels of anti-β2Glycoprotein-I or anticardiolipin (IgG/IgM) 10-30 GPL/MPL] with no previous evidence of LA positivity. aPL testing was performed blindly in 4 centers undertaking periodic external quality assessment. The 60 patients enrolled were distributed as follows: 43 (71.7%) with thrombotic APS, 7 (11.7%) with thrombosis and inconstant LA positivity and 10 (16.7%) with low-medium aPL titers. Categorical agreement for LA among the centers ranged from 0.41 to 0.60 ( coefficient; moderate agreement). The correlation determined at the 4 sites for aPS/PT was strong, both quantitatively (Spearman rho 0.84) and when dichotomized ( coefficients = 0.81 to 1.0). Discordant (as defined by lack of agreement in ≥3 laboratories) or inconclusive LA results were observed in 27/60 (45%) cases; when limiting the analysis to those receiving vitamin K antagonist (VKA), the level of discordant LA results was as high as 75%(15/20). Conversely, aPS/PT testing showed an overall agreement of 83% (up to 90% in patients receiving VKA), providing an overall increase in test reproducibility of +28% when compared to LA, becoming even more evident (+65%) when analyzing patients on VKA. In patients treated with VKA, we observed a good correlation for aPS/PT IgG testing ( coefficients = 0.81-1; Spearman rho 0.86). Despite the progress in the standardization of aPL testing, we observed up to 45% of overall discrepant results for LA, even higher in patients on VKA. The introduction of aPS/PT testing might represent a further diagnostic tool, especially when LA testing is not available or the results are uncertain.
狼疮抗凝物（LA）检测的一个主要缺点是其对抗凝治疗的敏感性，这是由于基于凝血的原理。在这项研究中，我们旨在评估 LA 检测的重现性，并评估固体测定磷脂酰丝氨酸/凝血酶原（aPS/PT）抗体的性能。我们纳入了 60 名符合以下纳入标准的患者：（I）血栓性抗磷脂综合征（APS）的诊断；（II）血栓形成患者，且（a）LA 先前阳性率不定和/或（b）抗磷脂抗体（aPL）低-中滴度阳性[定义为抗-β2糖蛋白-I 或抗心磷脂（IgG/IgM）水平为 10-30 GPL/MPL]，且无 LA 先前阳性的证据。aPL 检测在 4 个中心进行，这些中心定期进行外部质量评估。纳入的 60 名患者分布如下：43 名（71.7%）为血栓性 APS，7 名（11.7%）为血栓形成且 LA 阳性率不定，10 名（16.7%）为低-中 aPL 滴度。中心间 LA 的分类一致性范围为 0.41 至 0.60（系数；中度一致）。在 4 个部位测定的 aPS/PT 相关性很强，无论是定量的（Spearman rho 0.84）还是二分的（系数=0.81 至 1.0）。在 60 例（45%）中观察到 LA 结果不一致（定义为≥3 个实验室的不一致）或不确定；当将分析仅限于接受维生素 K 拮抗剂（VKA）的患者时，LA 结果不一致的水平高达 75%（15/20）。相反，aPS/PT 检测的总符合率为 83%（在接受 VKA 的患者中高达 90%），与 LA 相比，检测重现性总体提高了+28%，当分析接受 VKA 的患者时，这种提高更为明显（+65%）。在接受 VKA 治疗的患者中，我们观察到 aPS/PT IgG 检测的相关性良好（系数=0.81-1；Spearman rho 0.86）。尽管在 aPL 检测的标准化方面取得了进展，但我们观察到 LA 的总体不一致结果高达 45%，在接受 VKA 的患者中更高。引入 aPS/PT 检测可能是一种进一步的诊断工具，特别是在 LA 检测不可用时或结果不确定时。
