羟氯喹可防治抗磷脂综合征的产科并发症

作者：Meroni PL，et al.

翻译：北医三院 刘畅

摘要：妊娠相关并发症是抗磷脂综合征的部分临床表现，消耗很大的社会和经济成本。抗血小板及抗凝药治疗可以在大部分人群中有效预防临床症状的出现。 然而，在标准化的治疗中仍有部分病人在怀孕时出现病情复发。 观察性研究和实录报道中提出了了针对这些难治性病例的额外治疗策略。在这些策略中，抗疟药尤其是羟氯喹，在治疗APS以及其他系统性自身免疫风湿病中越来越被人们所关注。 抗疟药有多重效能，有包括免疫调节、抗炎、抗栓等活性。此外，羟氯喹在妊娠中使用安全，因此应用于包括APS在内的有自身免疫疾病的怀孕妇女中，并在观察性研究中发现了其对妊娠期疾病复发的保护性作用。由于血栓形成并不是产科APS的主要发病机制，因此说明羟氯喹在治疗中发挥了其除外抗血小板及抗栓作用以外的药理作用。在实验模型中发现，羟氯喹可以减轻抗磷脂抗体在滋养层细胞上产生的破坏效应，一个近期的研究中也报道了羟氯喹在aPL介导的胎盘缺陷及胎儿神经发育缺陷中的保护作用。尽管羟氯喹应用于产科APS的机理充分，但来自于临床的证据仍不具有决定性，更加严格的有效性研究势在必行。

附原文：Abstract：Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine(HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory.

引自：Meroni PL，et al. Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for? J Autoimmun. 2016 Aug 2. pii: S0896-8411(16)30101-9. doi: 10.1016/j.jaut.2016.07.003.