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抗血栓治疗与妊娠并发症:精准医学之旅的哪条路径?

Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

机构信息

Faculty of Health & Life Sciences, University of Liverpool, Liverpool, UK.

出版信息

Br J Haematol. 2014 Jun;165(5):585-99. doi: 10.1111/bjh.12813. Epub 2014 Mar 5.

Abstract

Haemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placenta-mediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.

摘要

止血和血管生物学机制似乎在胎盘介导的妊娠并发症发病机制中发挥重要作用。尽管小剂量阿司匹林 (LDA) 在预防子痫前期方面有一定效果,但抗血栓干预、LDA 和低分子肝素 (LMWH) 并未在单独以前次妊娠结局选择的胎盘介导的妊娠并发症妇女中明确证明其有效性。鉴于胎盘介导的妊娠并发症的病因异质性,根据母体和胎儿特征以及疾病机制对患者进行分层至关重要,而不仅仅是根据妊娠结局(如流产)。这种分层可以确定那些可能受益于妊娠中抗血栓干预的患者。我们缺乏全基因组关联研究、生物标志物和针对特定同质人群的干预措施的临床试验数据。未来的研究应侧重于阐述不同的疾病机制,并在特定和更同质的人群中检查抗血栓干预措施,例如具有明确胎盘介导的妊娠并发症的血栓形成倾向妇女,按疾病严重程度和病理发现分层。由于新型抗凝剂对胎儿安全性的担忧,干预措施应仅集中在肝素或与 LDA 联合使用上。因此,胎盘介导的妊娠并发症需要精准医学,通过机制而不是结局来定义疾病,干预措施侧重于更个性化的方法。

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