Crosstalk between inflammation and coagulation: Focus on pregnancy related complications

Thrombo-inflammatory mechanisms have emerged as an important interaction between the hemostatic and inflammatory systems, partially unrelated to blood clotting (the formation of fibrin-platelet aggregates). An interaction of platelets with other cell types is an integrated part of this crosstalk activating inflammatory signaling cascades in target cells and promoting cellular and organ dysfunction. These mechanisms are relevant during pregnancy where they convey patho-physiological effects at the maternal-embryonic interface thereby impairing placentation and pregnancy. Platelet activation activates pro-inflammatory mechanisms at the feto-maternal interface such as the NLRP3 inflammasome which in turn decreases thrombomodulin expression and impairs placental function. Coagulation regulators such as thrombomodulin and endothelial protein C receptor are required for embryonic development. Their loss results in activation of both coagulation system as well as inflammatory mechanisms. Similarly, anti-phospholipid antibodies elicit platelet activation and thrombo-inflammation, which facilitates a crosstalk between hemostatic and complement systems. The thrombo-inflammatory mechanisms not only result in pregnancy associated complications but can have a long-term impact on maternal and fetal health thereby predisposing them to chronic diseases later in life. Therefore, targeting these mechanisms is expected to prevent intra-uterine priming for diseases later in life, constituting a potential therapeutic strategy to prevent chronic diseases.