The First I.M. Sechenov Moscow State Medical University (Sechenov University), Moscow, Russia.
Unit of Rheumatology and Clinical Immunology, ASST Spedali Civili, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):6157-6164. doi: 10.1080/14767058.2021.1908992. Epub 2021 May 27.
The current recommended therapy of obstetric antiphospholipid syndrome (APS) is a long-term anticoagulant therapy that affects the final event, namely, when the thrombosis has already occurred. Unfortunately, this schedule is not always effective and fails despite the correct risk stratification and an adequate adjusted dose.
From 2013 to 2020 we observed 217 women with antiphospholipid antibodies and obstetric morbidities who were treated with conventional treatment protocol (aspirin low doses ± LMWH). Among them 150 (69.1%) successfully completed pregnancy with delivery and live birth on the background of LMWH and aspirin therapy and in 67 (30.9%) women despite a traditional therapy regimen, obstetric complications were noted. Later, 56 of these 67 women became pregnant again and were offered traditional therapy plus hydroxychloroquine. Fifteen women refused HCQ treatment due to possible potential side effects. The final cohort consisted of 41 women with positive antiphospholipid antibodies and obstetric and thrombotic complications who received LMWH, aspirin low doses and HCQ at a dose of 200-400mg per day from the beginning of pregnancy.
Forty-one aPL women treated with HCQ after failed previous anticoagulant therapy had live births in 32 cases (78%). Adding of HCQ to the combination of LMWH and LDA showed good overall obstetric results and increased the number of live births in another 32 women. So, a total of 182 (83.8%) of initial 217 aPL-women ended their pregnancies with live birth after adding the HCQ to the traditional therapy with LMWH and low doses of aspirin.
In 20-30% of cases the live birth despite anticoagulation cannot be achieved. Perhaps APS is not just anticoagulation. The study of pathophysiological mechanisms suggests that some patients will benefit from other therapy (in addition to anticoagulant). Therapy that affects the early effects of aPL on target cells (monocytes, endothelial cells, etc.) or before binding to receptors-this therapy will be preferable and potentially less harmful than the officially accepted one to date. From this point of view, HCQ looks promising and can be used as an alternative candidate for women with refractory obstetric antiphospholipid syndrome. Adding HCQ should be considered in some selected patients with failed pregnancy after treatment with anticoagulants.
目前，产科抗磷脂综合征（APS）的推荐治疗方法是长期抗凝治疗，这种治疗方法针对的是已经发生的血栓事件。不幸的是，尽管进行了正确的风险分层和充分的剂量调整，这种治疗方案并不总是有效。
我们观察了 2013 年至 2020 年间患有抗磷脂抗体和产科合并症的 217 名妇女，她们接受了常规治疗方案（低剂量阿司匹林+低分子肝素）。其中 150 名（69.1%）妇女在接受低分子肝素和阿司匹林治疗后成功妊娠并分娩活产，而在 67 名（30.9%）妇女中，尽管采用了传统治疗方案，但仍出现了产科并发症。后来，这 67 名妇女中有 56 名再次怀孕，并接受了传统治疗加羟氯喹。由于可能存在潜在的副作用，有 15 名妇女拒绝接受 HCQ 治疗。最终的队列由 41 名患有抗磷脂抗体和产科及血栓并发症的妇女组成，她们从妊娠开始就接受低分子肝素、低剂量阿司匹林和每天 200-400mg 的羟氯喹治疗。
在先前抗凝治疗失败的情况下接受 HCQ 治疗的 41 名抗磷脂抗体妇女中有 32 例（78%）活产。在低分子肝素和低剂量阿司匹林联合治疗的基础上添加 HCQ ，显示出良好的整体产科结局，并使另外 32 名妇女的活产率增加。因此，在最初的 217 名抗磷脂抗体妇女中，共有 182 名（83.8%）在添加 HCQ 到传统的低分子肝素和低剂量阿司匹林治疗后，成功妊娠并分娩活产。
尽管进行了抗凝治疗，仍有 20-30%的病例无法实现活产。也许 APS 不仅仅是抗凝治疗。对病理生理机制的研究表明，一些患者将受益于其他治疗方法（除抗凝治疗之外）。影响抗磷脂抗体早期作用于靶细胞（单核细胞、内皮细胞等）或与受体结合之前的治疗方法（这种治疗方法将优于目前官方认可的治疗方法），可能更具前景，且潜在危害更小。从这一点来看，羟氯喹很有前途，可以作为难治性产科抗磷脂综合征妇女的替代候选药物。对于接受抗凝治疗后妊娠失败的某些选定患者，应考虑添加羟氯喹。
