The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta.
The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta.
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DOI：
10.3390/ijms22136985
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发表时间：
2021-06-29
影响因子：
5.6
通讯作者：
Strauss JF 3rd
中科院分区：
文献类型：
--
作者：
Walsh SW;Strauss JF 3rd
20世纪80年代，人们发现先兆子痫妇女胎盘中血栓素增加，前列环素减少，从而开始了低剂量阿司匹林治疗先兆子痫的研究。当时，低剂量阿司匹林治疗被用于预防复发性心肌梗死和其他血栓形成事件，这是基于其选择性抑制血栓素合成而不影响前列环素合成的能力。随着血栓素在先兆子痫妇女中增加的发现，评估低剂量阿司匹林是否能有效预防先兆子痫是合理的。最初的临床试验非常有希望，但随后的两项大型多中心试验抑制了人们的热情，直到荟萃分析研究显示阿司匹林是有效的，但有警告。低剂量阿司匹林在100 mg/天开始时最有效<16 weeks of gestation and at doses >。它能有效减少早产儿先兆子痫，但不能减少足月儿先兆子痫，患者依从性和患者体重是重要变量。尽管低剂量阿司匹林治疗在纠正胎盘血栓素和前列环素之间的不平衡和减少氧化应激方面有效，但一些阿司匹林治疗的妇女仍然发生先兆子痫。胎盘鞘脂和羟基二十碳四烯酸的改变不受阿司匹林的影响，但具有可能导致先兆子痫的生物学作用，可能解释治疗失败。应考虑阿司匹林对中性粒细胞和妊娠特异性蛋白酶激活受体1表达的影响，以及预防先兆子痫的其他作用机制。
The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started <16 weeks of gestation and at doses >100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin’s effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.
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