Role of the Microparticles and of Tissue Factor in the Pro-thrombotic Phenotype and the Thromboembolic Complications During the Acute Lymphoblastic Leukemia in Children.

Overview

Acute lymphoblastic leukemia is the most common malignancy of the child. Current therapeutic strategies allow healing of over 80% of children. However these treatments are associated with toxicity, with a mortality of 1-2%. The most frequent complications, occuring during treatment initiation, are the thromboembolic complications. The most commonly accepted explanation is that of an anti-thrombin depletion by chemotherapy used in the treatment, L-asparaginase. But the anti-thrombin supplementation showed no efficacy in the prevention of these thromboembolic complications. Therefore most authors consider that a multifactorial mechanism is behind these events, involving both treatment and malignant cells. The interaction of these two factors participate in the damage of the vascular endothelium. The microparticles are membrane fragments derived from budding from the membrane of activated cells or apoptosis. Their thrombogenic role is linked to the expression of coagulation activators such as tissue factor. It is also associated with their role in the modulation of signaling pathways involved in the invasiveness and angiogenesis in endothelial cells. In acute lymphoblastic leukemia, the presence and role of microparticles have not been studied. Our hypothesis is that of production of microparticles upon lysis of blasts then upon activation of endothelial cells induced by the induction therapy, participating in a procoagulant phenotype.

The aims of this study are * quantify the microparticles in children receiving induction therapy for Acute lymphoblastic leukemia at diagnosis and during treatment * study the origin of these particles and the expression and activity of the tissue factor on their surface, at diagnosis and during treatment