Placental hemostasis and sterile inflammation: New insights into gestational vascular disease

Activation of the coagulation and inflammatory systems are physiologically occurring during pregnancy. However, excess activation of either system is well documented in gestational vascular diseases (GVD). GVD are placenta-mediated pregnancy complications and a major cause of feto-maternal morbidity and mortality. The causal relevance of excess coagulation and inflammatory responses for GVD remains largely unknown. Deciphering the causal relationship of excess coagulation and inflammation in GVD may allow conceptualizing new therapeutic approaches to combat GVD. Platelet activation and procoagulant extracellular vesicles (EVs) provide a link between coagulation and inflammation and their activation or generation in GVD is well established. As recently shown EVs cause sterile placental inflammation by activating maternal platelets that release ATP and activate purinergic receptor signaling and NLRP3 inflammasome in the embryonic trophoblast. This thrombo-inflammatory mechanism suggests a novel link between coagulation activation and sterile inflammation in GVD. These findings highlight a role of anti-platelet therapies in GVD. In addition, targeting the inflammasome alone or in combination with platelet inhibition may provide a new therapeutic strategy in GVD.