产科抗磷脂综合征(OAPS)是一种与各种病理性妊娠相关的自身免疫性疾病,例如复发性流产,死产,重度子痫前期和重度胎盘功能不全。抗磷脂抗体(aPL)的持续存在是OAPS最重要的实验室特征。OAPS严重影响中国育龄妇女的生殖健康。报告显示,大约9.6%的死胎,11.5%重度子痫前期,54%的复发性流产与OAPS或aPL有关。然而,OAPS的发病机制尚不清楚。以前,母胎界面血栓形成(MFI)被认为是OAPS相关病理性妊娠的主要机制.因此,建议在整个妊娠期间使用低分子量肝素和阿司匹林,以改善OAPS患者的结局.近年来,许多研究发现MFI中的血栓形成并不常见,但各种炎症因子在OAPS患者的MFI中显著升高。基于这些发现,一些临床医生已经开始使用抗炎治疗OAPS,初步改善了妊娠结局。然而,对于OAPS的这些二线治疗方法尚无共识。另一个令人不安的问题是OAPS的临床诊断。类似于其他自身免疫性疾病,只有OAPS的分类标准,OAPS的临床诊断取决于临床医生的经验。目前的OAPS分类标准是为临床和基础研究目的而建立的,不适用于患者临床管理。在临床实践中,许多aPL阳性且有病理妊娠史的患者不符合严格的OAPS标准.这导致了不正确的诊断和治疗的广泛问题。及时准确诊断OAPS是有效治疗的关键。在这篇文章中,综述了OAPS的流行病学研究进展,总结了OAPS的分类原则,包括:1)循环中持续存在的aPL;2)OAPS的表现,排除其他可能的原因。对于第一点,对aPLs的准确评估是至关重要的;对于后者来说,以往的研究仅将胎盘相关妊娠并发症视为OAPS的特征性表现.然而,最近的研究表明,不良妊娠结局与滋养细胞损伤有关,例如复发性流产和死胎,在OAPS中也需要考虑。我们还讨论了OAPS诊断和治疗中的几个关键问题。首先,我们讨论了非标准OAPS的定义,并提出了在2023年美国风湿病学会(ACR)/欧洲抗风湿病联盟(EULAR)APS标准框架内定义非标准OAPS的意见.然后,我们讨论了不同的aPL测试方法的优缺点,强调跨平台协调结果和建立特定的参考值是解决aPL测试结果争议的关键。我们还介绍了非标准不良贷款的应用,特别是抗磷脂酰丝氨酸/凝血酶原抗体(aPS/PT)和抗β2糖蛋白Ⅰ结构域Ⅰ抗体(aβ2GPⅠDⅠ)。此外,我们讨论了基于aPL的OAPS风险分类策略。最后,我们提出了难治性OAPS的潜在治疗方法。旨在为OAPS的临床管理提供参考。
Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in
China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians\' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-β2 glycoprotein Ⅰ domain Ⅰ antibody (aβ2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.