Agbani Ejaife O, Skeith Leslie, Lee Adrienne
Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Alberta, Canada.
Libin Cardiovascular Institute, Calgary, Alberta, Canada.
Res Pract Thromb Haemost. 2023 Feb 8;7(2):100075. doi: 10.1016/j.rpth.2023.100075. eCollection 2023 Feb.
A state-of-the-art lecture titled "Preeclampsia and Platelet Procoagulant Membrane Dynamics" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2022. Platelet activation is involved in the pathophysiology of preeclampsia and contributes to the prothrombotic state of the disorder. Still, it remains unclear what mechanisms initiate and sustain platelet activation in preeclampsia and how platelets drive the thrombo-hemorrhagic abnormalities in preeclampsia. Here, we highlight our findings that platelets in preeclampsia are preactivated possibly by plasma procoagulant agonist(s) and overexpress facilitative glucose transporter-3 (GLUT3) in addition to GLUT1. Preeclampsia platelets are also partially degranulated, procoagulant, and proaggregatory and can circulate as microaggregates/microthrombi. However, in response to exposed subendothelial collagen, such as in injured vessels during cesarean sections, preeclampsia platelets are unable to mount a full procoagulant response, contributing to blood loss perioperatively. The overexpression of GLUT3 or GLUT1 may be monitored alone or in combination (GLUT1/GLUT3 ratio) as a biomarker for preeclampsia onset, phenotype, and progression. Studies to further understand the mediators of the platelet activation and procoagulant membrane dynamics in preeclampsia can reveal novel drug targets and suitable alternatives to aspirin for the management of prothrombotic tendencies in preeclampsia. Finally, we summarize relevant new data on this topic presented during the 2022 ISTH Congress.
一场题为“子痫前期与血小板促凝膜动力学”的前沿讲座于2022年在国际血栓与止血学会（ISTH）大会上发表。血小板活化参与子痫前期的病理生理过程，并促成该病症的血栓前状态。然而，子痫前期中启动并维持血小板活化的机制以及血小板如何引发子痫前期的血栓-出血异常仍不清楚。在此，我们着重介绍我们的研究发现：子痫前期患者的血小板可能被血浆促凝激动剂预激活，除葡萄糖转运蛋白1（GLUT1）外，还过度表达葡萄糖转运蛋白3（GLUT3）。子痫前期患者的血小板还会部分脱颗粒、具有促凝性和促聚集性，并能以微聚集体/微血栓的形式循环。然而，在剖宫产术中暴露于内皮下胶原（如受损血管中的内皮下胶原）时，子痫前期患者的血小板无法产生充分的促凝反应，导致围手术期失血。GLUT3或GLUT1的过度表达可单独或联合监测（GLUT1/GLUT3比值），作为子痫前期发病、表型和进展的生物标志物。进一步了解子痫前期血小板活化和促凝膜动力学介质的研究可以揭示新的药物靶点，以及用于管理子痫前期血栓形成倾向的阿司匹林合适替代物。最后，我们总结了2月22日ISTH大会期间发表的关于该主题的相关新数据。
