The Relation between Plasma Levels of Thrombomodulin and Endothelial Dysfunction in Syrian Children with Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancies, representing nearly one-third of all pediatric cancers. Thrombomodulin is a membrane glycoprotein expressed on endothelial cells, Its plasma level depends on the integrity of the endothelium. Soluble thrombomodulin is derived from injured endothelial cells or proteolytically cleaved from thrombomodulin by proteases. In the past, the endothelium was considered to be inert, described as a 'layer of nucleated cellophane', with only non-reactive barrier properties. However, it is now becoming clear that endothelial cells actively and reactively participate in hemostasis and immune and inflammatory reactions. They regulate vascular tone via production of nitric oxide, endothelin and prostaglandins. Severe endothelial dysfunction is present during the acute phase of acute lymphoblastic leukemia and it result from the disease itself, from treatment, or from other conditions (e.g. sepsis). Objective:The aim of this study was to determine the level of serum soluble thrombomodulin as a marker of endothelial activation in children with ALL at time of diagnosis and after the chemotherapy. Methods and Materials: A case - control study included Thirty patients with ALL and twenty healthy children. We analyzed serum soluble thrombomodulin levels by enzyme-linked immunosorbent assay. Results: In children with acute lymphoblastic leukemia, there was a significant increase in soluble thrombomodulin levels during the acute phase of the disease and during treatment. Conclusion: severe endothelial dysfunction is present during the acute phase of ALL and during treatment and appears to result from the disease itself and from the treatment.