子痫前期
血小板
血小板活化
内科学
内分泌学
医学
磷脂酰丝氨酸
凝血酶
怀孕
化学
生物
生物化学
磷脂
膜
遗传学
作者
Ejaife O. Agbani,Lorraine Chow,Joshua Nicholas,Leslie Skeith,Prism Schneider,Alexander J. Gregory,Etienne Mahé,Lisa Yamaura,David Young,Antoine Dufour,Padma Polash Paul,A. Earl Walker,Priyanka G. Mukherjee,Alastair W. Poole,Man‐Chiu Poon,Adrienne Lee
标识
DOI:10.1016/j.jtha.2023.03.014
摘要
Background Preeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. Objectives We aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. Methods In this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. Results PE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets’ expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. Conclusions We revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.
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