O001: Thrombomodulin regulates platelet and extracellular vesicle mediated sterile inflammation in the placenta

Scientific Research Question: Thrombomodulin (TM) deficiency causes tissue-factor initiated thrombin generation, maternal platelet-activation and embryonic lethality in mice. However, the mechanism remains poorly understood. We have recently shown that procoagulant extracellular vesicles (EVs) activate maternal platelets, which results in purinergic receptor mediated inflammasome activation in the trophoblast and subsequently preeclampsia (PE). We therefore investigated whether this EV-mediated thrombo-inflammatory pathway in placenta is controlled by thrombomodulin and whether this mechanism contributes to the lethality of TM null embryos.