the Coagulolytic Balance clinical trials

Interest of the Balance of Pro-coagulating and Profibrinolytis Activities of the Microparticles (MP) in the Prognosis of Septic Shock

Septic shock is a clinical syndrome occurring in 10 to 20% of patients admitted in ICV. Mortality associated to septic shock varies from 30 to 50%. It follows a systemic response of the organism to a severe infection, associated with a circulatory failure marker by an arterial hypotension and a vascular hyperactivity to vasoconstrictor agents. The mechanisms involved on one hand an activation of white blood cells inflammatory system and the vascular inflammatory system; and on the other hand on imbalance in hemostatis characterized by an activation of the coagulation and an inappropriate fibrinolysis leading to a disruption of microcirculation in the context of a disseminated intravascular coagulation (DIVC). This inflammatory and thrombotic cellular activation is strongly associated with the phenomenon of vesiculation; leading to the production of cellular microparticles (MP) by blood cells and vascular cells. MP are membranous vesicles, resulting in the reassortment of membrane phospholides in response to an activation of cellular apoptosis. They have been initially described as new actors of hemostatis. Indeed, the expression of phospholipid serine and tissular factor (TF) confer them a procoagulating activity, which increases in patients undergoing septic shock. The finding of a fibriniolytic activity of the cellular MP suggests the existence of compensating mechanisms with a procoagulating activity. This confers to MP a key-role in the control of the coagulolytic balance. Our recent researches suggest that endothelial and white blood cells MP produce in vivo plasmin. They carry into the main circulation a fibrinolytic activity which is partially beyond the physiological inhibitors activity (PAI-1, x 2 antiplasmin). Preliminary findings show that this ability of plasmin generation is important in patients affected with septic shock. Our hypothesis is that an increase in plasmin generation by MP compensates the risk of occurrence of microthrombosis, modulating therefore the vital prognosis of patients with septic shock. The coagulolytic balance of MP, which is resulting of their own procoagulating and fibrinolytic activities could claim the status of new pronostic marker relevant in patients with septic shock.