Risk factors and recurrent thrombosis in primary antiphospholipid syndrome

Fariza A. Cheldieva, Anastasiia A. Shumilova, Mariya V. Cherkasova, Svetlana I. Glukhova, Aleksander M. Lila, Evgeny L. Nasonov, Tatiana M. Reshetnyak
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Abstract

Aim: The study aims to evaluate the incidence of recurrent thromboses in patients with primary antiphospholipid syndrome (PAPS) and its association with the presence of different antiphospholipid antibodies (aPLs) and known thrombogenic risk factors. Methods: This retrospective study included 52 patients. The median age of the patients was 38.5 years [31.5; 43.5], and the duration of the disease was 9.0 years [3.1; 13.0]. aPLs, including IgG/IgM/IgA antibodies to cardiolipin (aCLs), IgG/IgM/IgA anti-beta2-glycoprotein I (anti-β2-GPI), IgG anti-domain I-β2-GPI (anti-β2-GPI DI) antibodies, IgG/IgM antibodies to the phosphatidylserine/prothrombin complex (aPS/PT), and other thrombosis risk factors were included for analysis. Results: Recurrent thrombosis was reported in 34 (65%) out of 52 patients and 18 (35%) did not have it. The main reason for the recurrence of thrombosis was the lack of anticoagulant therapy: in 18 (52.9%) out of 34 patients with recurrent thrombosis. Three patients were taking warfarin at the time of thrombosis recurrence, but target international normalized ratio (INR) levels were not achieved. Other patients with recurrent thrombosis were taking direct oral anticoagulants (DOACs). The risk of recurrent thrombotic events with positive IgG aCL was 10.33 (P = 0.002) and 21 (P = 0.007) times higher were examined in enzyme-linked immunoassay (ELISA) and chemiluminescent assay (CLA), respectively. The risk of thrombosis was 4.58 times higher in patients who were IgA aCL-positive (P = 0.01). Compared with other antibodies, with positive IgG values of anti-β2-GPI and IgG aPS/PT by ELISA, a lower probability of thrombosis recurrence was observed: 7.56 and 7.25, respectively. A high risk of recurrent thrombosis [odds ratio (OR) = 32.0] was observed in IgG anti-β2-GPI (CLA). The combination of IgG aCL with IgG anti-β2-GPI and with IgG anti-β2-GPIDI is more informative with respect to the risks of thrombosis recurrence compared to double positivity for aCL with anti-β2-GPI (OR = 20.71 vs. OR = 10.18). Triple positivity for IgG aCL with IgG anti-β2-GPI and with IgG aPS/PT also shows better results compared to positivity for aCL with anti-β2-GPI (OR = 6.06 vs. OR = 5.79). Among other risk factors, arterial hypertension (AH) and obesity were significant in relation to the recurrence of thrombosis. AH occurred in 22 (42%) of 52 patients with PAPS. AH was associated with recurrent thrombosis in PAPS patients: 18 (53%) out of 34 with recurrent thrombosis had AH versus 4 out of 18 without recurrent thrombosis (P = 0.003). Conclusions: Recurrent thrombosis in antiphospholipid syndrome (APS) is largely associated with IgG aCL, IgG anti-β2-GPI, IgG anti-β2-GPIDI, IgG aPS/PT, and IgA aCL positivity. AH was a significant risk factor for recurrent thrombosis.
原发性抗磷脂综合征的危险因素与血栓复发
目的:本研究旨在评估原发性抗磷脂综合征(PAPS)患者复发性血栓的发生率及其与不同抗磷脂抗体(apl)和已知血栓形成危险因素的关系。方法:回顾性研究52例患者。患者的中位年龄为38.5岁[31.5;43.5],病程9.0年[3.1;13.0]。包括IgG/IgM/IgA抗心磷脂(aCLs)抗体、IgG/IgM/IgA抗β -糖蛋白I(抗β2- gpi)抗体、IgG抗结构域I-β2-GPI(抗β2- gpi DI)抗体、IgG/IgM抗磷脂酰丝氨酸/凝血酶原复合物(aPS/PT)抗体等血栓形成危险因素进行分析。结果:52例患者中34例(65%)复发血栓形成,18例(35%)无复发血栓形成。34例再发血栓患者中18例(52.9%)为未给予抗凝治疗。3例患者在血栓复发时正在服用华法林,但未达到国际标准化比率(INR)目标水平。其他复发性血栓患者直接口服抗凝剂(DOACs)。IgG aCL阳性患者的血栓事件复发风险分别是ELISA和CLA的10.33倍(P = 0.002)和21倍(P = 0.007)。IgA - acl阳性患者血栓形成风险高4.58倍(P = 0.01)。与其他抗体相比,ELISA检测抗β2- gpi IgG阳性和IgG aPS/PT阳性的患者血栓复发概率较低,分别为7.56和7.25。抗β2- gpi (CLA) IgG有较高的血栓复发风险[OR = 32.0]。与抗β2- gpi双阳性aCL相比,IgG aCL与IgG抗β2- gpi和IgG抗β2- gpidi联合检测在血栓复发风险方面更具信息性(OR = 20.71 vs OR = 10.18)。IgG aCL与IgG抗β2- gpi和IgG aPS/PT的三重阳性也比抗β2- gpi的aCL阳性显示更好的结果(OR = 6.06 vs OR = 5.79)。在其他危险因素中,动脉高血压(AH)和肥胖与血栓复发有显著关系。52例PAPS患者中22例(42%)发生AH。AH与PAPS患者血栓复发相关:34例血栓复发患者中有18例(53%)有AH, 18例无血栓复发患者中有4例(P = 0.003)。结论:抗磷脂综合征(APS)复发性血栓形成与IgG aCL、IgG抗β2- gpi、IgG抗β2- gpidi、IgG APS /PT、IgA aCL阳性有很大关系。AH是复发性血栓形成的重要危险因素。
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