Thromboinflammation and the Role of Platelets

IntroductionThrombo-inflammation is a pathological condition characterized by the concurrence of thrombosis, inflammation, and vascular leakage/bleeding, which induce and exacerbate each other leading to tissue/organ injury and death.Thrombo-inflammation may occur in a wide range of inflammatory and cardiovascular/pulmonary diseases, including severe infection (e.g.sepsis and severe COVID19), acute respiratory distress syndrome, ischemia-reperfusion injury following myocardial infarction, organ transplant and acute kidney ischemia, cardiac arrest, severe injury, autoimmune diseases, thrombosis (e.g.deep vein thrombosis), and atherosclerosis 1,2 .Thrombo-inflammation can be acute and chronic and can be severe with high mortality and morbidity.Despite many years of intensive efforts and development of many anti-inflammatory and anti-thrombotic drugs, there is still no current drug available that is convincingly effective in the treatment of thrombo-inflammation.The reason for the ineffectiveness of many anti-inflammatory and anti-thrombotic drugs is unclear.However, past and recent studies and clinical trials shed mechanistic light and raise hopes for new therapeutic concepts and drugs.Here we briefly discuss our perspectives with an emphasis mainly on severe acute thrombo-inflammation. Good clot, bad clot, good inflammation, bad inflammation.Thrombo-inflammation is the manifestation of dysregulation of the two most important defensive and wound healing responses of the body: inflammation and hemostasis 3 .Both hemostasis and inflammation are highly regulated processes and are dynamically balanced.Shifting the balance towards either direction causes pathological states.Hemostatic responses to injury or blood vessel leakage activate platelets and the coagulation system, which together form hemostatic thrombi ("clots") to seal the wound, minimizing blood loss and microbial invasion.Deficiency in either platelets or coagulation causes blood vessel leakage and bleeding, whereas overreaction of platelets or coagulation causes formation of thrombi that occlude blood vessels, termed thrombosis.Inflammation as a part of innate immunity can be triggered by molecular patterns from microbials and damaged tissue/ cells, antibody-antigen interaction, and cytokines released or generated during hemostatic