Masaryk Hospital Usti nad Labem, Department Clinical Hematology, 40113 Usti nad Labem, Czech Republic.
Department of Hemato-Oncology, Faculty of Medicine and Dentistry, University Hospital Olomouc, Palacky University Olomouc, 77900 Olomouc, Czech Republic.
Int J Mol Sci. 2022 Aug 11;23(16):8973. doi: 10.3390/ijms23168973.
Antiphospholipid syndrome (APS) is a hypercoagulable state accompanied by the presence of heterogeneous antiphospholipid antibodies (aPL), which nonspecifically affect hemostasis by the presence of lupus anticoagulans (LA), anticardiolipin antibodies (aCL), antibodies against β2-glycoprotein-I (anti-β2GPI), but also non-criteria antibodies such as antibodies against β2-glycoprotein-I domain I (anti-DI), anti-phosphatidylserine/prothrombin (anti-PS/PT), anti-annexin V, and many others. The main target of the antibodies is the activated protein C (APC) system, the elimination of which can manifest itself as a thrombotic complication. The aim of this study was to determine the thrombogenicity of antibodies using a modified protein C-activated thrombin generation assay (TGA) on a group of 175 samples suspected of APS. TGA was measured with/without APC and the ratio of both measurements was evaluated (as for APC resistance), where a cut-off was calculated ≤4.5 (90th percentile) using 21 patients with heterozygous factor V Leiden mutation (FV Leiden heterozygous). Our study demonstrates the well-known fact that multiple positivity of different aPLs is a more severe risk for thrombosis than single positivity. Of the single antibody positivity, LA antibodies are the most serious (p value < 0.01), followed by aCL and their subgroup anti-DI (p value < 0.05). Non-criteria antibodies anti-annexin V and anti-PT/PS has a similar frequency occurrence of thrombogenicity as LA antibodies but without statistical significance or anti-β2GPI1 positivity. The modified TGA test can help us identify patients in all groups who are also at risk for recurrent thrombotic and pregnancy complications; thus, long-term prophylactic treatment is appropriate. For this reason, it is proving increasingly beneficial to include the determination antibodies in combination with modified TGA test.
抗磷脂综合征（APS）是一种高凝状态，伴有多种抗磷脂抗体（aPL）的存在，狼疮抗凝物（LA）、抗心磷脂抗体（aCL）、β2-糖蛋白 I 抗体（anti-β2GPI）等非特异性影响止血，但也有非标准抗体，如β2-糖蛋白 I 结构域 I 抗体（anti-DI）、抗磷脂酰丝氨酸/凝血酶原（anti-PS/PT）、抗膜联蛋白 V 等。抗体的主要靶标是活化蛋白 C（APC）系统，其消除可表现为血栓并发症。本研究旨在使用改良的蛋白 C 激活凝血酶原生成试验（TGA），在一组 175 例疑似 APS 的样本中，确定抗体的血栓形成性。TGA 分别在有/无 APC 的情况下进行测量，并评估两者测量的比值（APC 抵抗），使用 21 例杂合子因子 V 莱顿突变（FV Leiden heterozygous）患者的 90%分位数计算出≤4.5 的截止值（cut-off）。我们的研究证明了一个众所周知的事实，即多种不同 aPL 的阳性比单一阳性是血栓形成的更严重风险。在单一抗体阳性中，LA 抗体最为严重（p 值<0.01），其次是 aCL 及其亚组 anti-DI（p 值<0.05）。非标准抗体抗膜联蛋白 V 和抗 PT/PS 的血栓形成频率与 LA 抗体相似，但无统计学意义或 anti-β2GPI1 阳性。改良的 TGA 试验可以帮助我们识别所有组别的患者，这些患者也有复发性血栓形成和妊娠并发症的风险；因此，长期预防性治疗是合适的。出于这个原因，将抗体的测定与改良的 TGA 试验结合起来证明越来越有益。
