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Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome
Background 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.
Objectives To investigate the clinical relevance of isolated LAC.
Methods 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 (n = 91), patients with thrombosis but without aPLs (n = 127), and normal controls (n = 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.
Results 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.
Conclusion 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.
Keywordsantiphospholipid antibodies - β2 glycoprotein I - lupus anticoagulant - prothrombin - thrombosis
K. M. J. Devreese and B. de Laat designed the study. K. M. J. Devreese collected samples and identified sample characteristics. Samples were analyzed under the supervision of K. M. J. Devreese. D. Yin interpreted the data, performed statistical analysis, and wrote the first version of the manuscript. P. G. de Groot, B. de Laat, K. M. J. Devreese, and Marisa Ninivaggi critically reviewed the manuscript.
Received: 22 September 2020
Accepted: 28 December 2020
31 December 2020 (online)
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
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