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血栓形成性抗磷脂综合征:复发性血栓形成

Thrombotic Antiphospholipid Syndrome: Recurrent Thromboses.

作者信息

Reshetnyak T M, Cheldieva F A, Glukhova S I, Nurbaeva K S, Seredavkina N V, Cherkasova M V, Lila A M, Nasonov E L

机构信息

Nasonova Research Institute of Rheumatology, Moscow, Russia.

Department of Rheumatology, Russian Medical Academy of Continuous Professional Education of the Ministry of Health Care of the Russian Federation, Moscow, Russia.

出版信息

Dokl Biochem Biophys. 2025 May 11. doi: 10.1134/S1607672925700152.

DOI:10.1134/S1607672925700152
PMID:40353960
Abstract

UNLABELLED

Thrombotic antiphospholipid syndrome (APS) is a condition affecting young people in whom a thromboembolic event occurs in the presence of circulating antiphospholipid antibodies (aPL).

THE AIM OF THIS STUDY

was to evaluate the incidence of recurrent thrombosis and its risk factors in antiphospholipid syndrome.

MATERIALS AND METHODS

. The retrospective study included 98 patients with APS who were followed up at the institute from 2014 to 2023, of whom 66 (67%) were women and 32 (33%) were men. Of the 98 patients with APS, 48 (49%) had a diagnosis of systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL), including the antibodies to cardiolipin (IgG/IgM aCL), antibodies to ß2glycoprotein 1 (IgG/IgM aß2GP1), antibodies to ß2 glycoprotein IgG against domain 1 (IgG aß2GP1-D1), antibodies to phosphatidylserine/prothrombin complex (IgG/IgM aPS/PT), and other thrombotic risk factors were determined. aPL was assessed by enzyme-linked immunosorbent assay (ELISA) and chemiluminescence assay (CLA).

RESULTS

: Thrombosis recurrence was reported in 62 (63%) of 98 patients, and in 36 (35%) it was not reported. The main cause of recurrent thrombosis was treatment with direct oral anticoagulants (DOACs). Twenty-four (38.7%) of  62 patients with recurrent thrombosis were treated with DOACs, the duration of which ranged from 6 to 24 months. The next most common cause of recurrent thrombosis was the lack of continuous anticoagulant therapy in 20 (32.5%) patients. In 17 (27.4%) patients, recurrence occurred while they were still taking warfarin. In 10 (41.7%) of the 24 patients, the recurrent thrombosis was arterial in origin. This was associated with recurrent cerebral circulation problems. The level of positivity for aPL did not matter, but all of them had triple IgG-aPL positivity. Five patients had lupus anticoagulant (LA) at the onset of the disease before anticoagulant therapy. IgG-aPS/PT was most important in association with recurring thrombosis in the ELISA: 45 (72.6%) of 62 patients with recurring thrombosis were positive for IgG-aPS/PT as compared with 19 (52.8%) of 36 patients without recurring thrombosis. The detection of all aPLs was more frequent in CLA than in ELISA. However, the determination of aPL by ELISA is recommended according to the latest classification criteria. Triple positivity for IgG aCL, IgG aß2GP1, and IgG aß2GP1-D1 according to CLA data remained a risk factor for recurrent thrombosis and increased the risk of recurrence more than 3 times. Obesity was a risk factor for recurrent thrombosis, with a 5-fold increased risk of recurrent thrombosis in obese patients compared to the non-obese ones (p = 0.01).

CONCLUSIONS

. Recurrent thrombosis in APS is largely associated with IgG aCL, IgG aß2GP1, IgG aß2GP1-D1, and IgG aPS/PT. Triple IgG aPL positivity in any combination significantly increased recurrent thrombosis risk. The presence of any type of IgG aPL in both ELISA and CLA influenced the recurrence rate of thrombosis in APS. Obesity was a significant risk factor for recurrent thrombosis.

摘要

未标注

血栓形成性抗磷脂综合征(APS)是一种影响年轻人的疾病,在存在循环抗磷脂抗体(aPL)的情况下发生血栓栓塞事件。

本研究的目的

是评估抗磷脂综合征中复发性血栓形成的发生率及其危险因素。

材料与方法

这项回顾性研究纳入了98例2014年至2023年在该研究所接受随访的APS患者,其中66例(67%)为女性,32例(33%)为男性。在98例APS患者中,48例(49%)诊断为系统性红斑狼疮(SLE)。检测了抗磷脂抗体(aPL),包括抗心磷脂抗体(IgG/IgM aCL)、抗β2糖蛋白1抗体(IgG/IgM aβ2GP1)、抗β2糖蛋白IgG针对结构域1的抗体(IgG aβ2GP1-D1)、抗磷脂酰丝氨酸/凝血酶原复合物抗体(IgG/IgM aPS/PT)以及其他血栓形成危险因素。aPL通过酶联免疫吸附测定(ELISA)和化学发光测定(CLA)进行评估。

结果

98例患者中有62例(63%)报告有血栓形成复发,36例(35%)未报告复发。复发性血栓形成的主要原因是使用直接口服抗凝剂(DOACs)治疗。62例复发性血栓形成患者中有24例(38.7%)接受了DOACs治疗,治疗持续时间为6至24个月。复发性血栓形成的第二常见原因是20例(32.5%)患者缺乏持续抗凝治疗。17例(27.4%)患者在仍服用华法林时发生复发。24例患者中有10例(41.7%)复发性血栓形成起源于动脉。这与反复出现的脑循环问题有关。aPL的阳性水平无关紧要,但所有患者均有三联IgG-aPL阳性。5例患者在抗凝治疗前疾病发作时存在狼疮抗凝物(LA)。在ELISA中,IgG-aPS/PT与复发性血栓形成最为相关:62例复发性血栓形成患者中有45例(72.6%)IgG-aPS/PT呈阳性,而36例无复发性血栓形成患者中有19例(52.8%)呈阳性。CLA检测所有aPL的频率高于ELISA。然而,根据最新分类标准,建议采用ELISA测定aPL。根据CLA数据,IgG aCL、IgG aβ2GP1和IgG aβ2GP1-D1三联阳性仍然是复发性血栓形成的危险因素,复发风险增加超过3倍。肥胖是复发性血栓形成的危险因素,肥胖患者复发性血栓形成的风险是非肥胖患者的5倍(p = 0.01)。

结论

APS中的复发性血栓形成在很大程度上与IgG aCL、IgG aβ2GP1、IgG aβ2GP1-D1和IgG aPS/PT有关。任何组合的三联IgG aPL阳性均显著增加复发性血栓形成风险。ELISA和CLA中任何类型IgG aPL的存在均影响APS中血栓形成的复发率。肥胖是复发性血栓形成的重要危险因素。

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