Yin Dongmei, de Groot Philip G, Ninivaggi Marisa, Devreese Katrien M J, de Laat Bas
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
Department of Functional Coagulation, Synapse Research Institute, Maastricht, The Netherlands.
Thromb Haemost. 2021 Sep;121(9):1220-1227. doi: 10.1055/a-1344-4271. Epub 2021 Mar 3.
Patients positive for all three types of antiphospholipid antibodies (aPLs; triple positivity) have been identified for having a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated.
To investigate the clinical relevance of isolated LAC.
A total of 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group consisted of autoimmune patients ( = 91), patients with thrombosis but without aPLs ( = 127), and normal controls ( = 172). LAC, anticardiolipin (anti-CL), and anti-β2 glycoprotein I (anti-β2GPI) immunoglobulin G (IgG) and immunoglobulin M (IgM) were determined according to the International Society on Thrombosis and Haemostasis (ISTH) guidelines. Anti-CL and anti-β2GPI were measured by four different solid-phase platforms to overcome variability between test systems. The noncriteria IgA anti-CL and anti-β2GPI, antidomain I of β2GPI IgG, and antiphosphatidylserine/prothrombin antibodies (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid-phase assays.
In total, 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL antibodies. We found that isolated LAC proved to be strongly associated with vascular thrombosis (odds ratio [OR]: 7.3; 95% confidence interval [CI]: 3.3-16.1), even better than triple-positive samples (OR: 4.3; 95% CI: 1.6-12.2). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple-positivity samples compared with samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT-negative. We observed that LAC positivity was weaker in isolated LAC-positive patients compared with LAC activity in triple-positive patients.
Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT antibodies could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared with triple-positive patients.
已确定所有三种抗磷脂抗体（aPLs）均呈阳性（三重阳性）的患者发生血栓事件的风险很高。然而，孤立性狼疮抗凝物（LAC）阳性的临床意义存在争议。
研究孤立性LAC的临床相关性。
本研究共纳入456例患者；66例抗磷脂综合征患者和390例对照患者。对照组包括自身免疫性疾病患者（n = 91）、有血栓形成但无aPLs的患者（n = 127）和正常对照者（n = 172）。根据国际血栓与止血学会（ISTH）指南测定LAC、抗心磷脂（抗CL）和抗β2糖蛋白I（抗β2GPI）免疫球蛋白G（IgG）和免疫球蛋白M（IgM）。采用四种不同的固相平台检测抗CL和抗β2GPI，以克服检测系统之间的差异。根据ISTH固相检测指南检测非标准的IgA抗CL和抗β2GPI、抗β2GPI IgG的结构域I抗体以及抗磷脂酰丝氨酸/凝血酶原抗体（抗PS/PT）IgG和IgM。
共有70例患者LAC呈阳性，其中44例抗β2GPI和抗CL抗体均为阴性。我们发现，孤立性LAC与血管血栓形成密切相关（比值比[OR]：7.3；95%置信区间[CI]：3.3 - 16.1），甚至优于三重阳性样本（OR：4.3；95% CI：1.6 - 12.2）。与孤立性LAC阳性样本相比，三重阳性样本中抗PS/PT IgG和IgM的滴度显著更高。大多数单一LAC阳性患者抗PS/PT为阴性。我们观察到，与三重阳性患者的LAC活性相比，孤立性LAC阳性患者的LAC阳性程度较弱。
孤立性LAC与血栓形成高度相关。抗PS/PT抗体的存在无法解释孤立性LAC中的LAC阳性。与三重阳性患者相比，孤立性LAC的LAC活性较弱。
