the Coagulolytic Balance Clinical Trial
Official title:
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.
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