Circulating Endothelial Microparticles (CD144+) and von Willebrand Factor Antigen as Markers of Endothelial Dysfunction in Young β-Thalassemia Major Patients

Abstract

SUMMARY P atients with beta thalassemia demonstrate an increased incidence of vascular complications, which are thought to result from a procoagulant/proinflammatory environment. There is strong evidence of endothelial cell activation in thalassemic patients, and vascular complications in these patients are more frequent. In recent years, the interest for endothelial microparticles (MPs) has substantially increased, not only because of their procoagulant properties but also because of their putative role in inflammatory processes and their ability to directly affect endothelial functions.Also plasma levels of VWF are raised indifferent states of endothelial damage andhave therefore been proposed as usefulmarkers of endothelial dysfunction. This study aimed to determine the quantity of circulating endothelial microparticles (CD144+cells) and serum von willebrand factor antigen (VWF ag) as markers of endothelial dysfunction in β-thalassemia patientsand assess their relationto iron overload state, transfusion history and markers of hemolysis of these patients. This case control study included 40 transfusion dependent β-thalassemia patients (aged between11-30 years with mean 15.36 ± 3.9 years, a male-to-female ratio 1 : 1.1) recruited from the Pediatric Hematology Clinic, Ain Shams University, compared to twenty age and sex-matched healthy controls. All included patients were subjected to detailed medical history including transfusion, chelation, hepatitis C virus history, with calculation of mean serum ferritin in last 2 years,through clinical examination, laboratory investigations included CBC, liver and kidney function tests, markers of hemolysis (total bilirubin, indirect bilirubin), flow cytometric analysis of endothelial microparticles (CD144+cells)and serum von willebrand factor antigen (VWF ag) using ELISA.Doppler echocardiography was done for all the included patients. In the current work,Beta thalassemia patients had significantly higher serum VWF ag level & quantity of endothelial microparticles (CD144+Cells) than control howeverboth β-thalassemia major and β-thalassemia intermedia Patients had comparable quantity of endothelial microparticles (CD144+Cells) & serum VWF ag levels. There were five Beta thalassemia patients with ejection fraction <60% (12.5%), five patients with Shortening fraction< 30% (12.5%) and eighteen with increased left ventricular diameter & all patients had normal right ventricular diameter and right ventricular pressure. Patients were divided into two groups according to mean serum ferritin in last 2 years:Group 1: included patients with mean serum ferritin less than 2500ng/dl in last 2 years prior evaluation. Group 2: included patients with mean serum ferritin more than or equal 2500 ng/dl in last 2 years prior evaluation. There were no significant differences between both groups as regard age & sex distribution, age at diagnosis, duration of the disease, consanguinity, and family history of thalassemia.However patients with mean serum ferritin > 2500 ng/mL in last 2 years prior evaluation showed higher rate of splenectomy.There were no significant differences between both groups asregard frequency of blood transfusion, type of transfused PRBCs, mean pretransfusion Hb in last 2 years and transfusion index. On the other hand our study revealed that there was no significant difference between both groups as regard quantity of circulatingendothelial microparticles (CD144+cells) yetpatients with mean serum ferritin >2500 in last 2 years prior evaluation had significant higher serum VWF ag level. Also no significant differences were found between both groups as regard echo-cardiography parameters. Both splenectomized and non splenectomized β-thalassemia patients had comparable quantity of endothelial microparticles (CD 144+Cells) & serum VWF ag levels. Both β-thalassemia patients on monotherapy and combined chelation therapy had comparable quantity of endothelial microparticles (CD144+Cells), serum VWF ag levels andechocardiography parameters. There were no significant correlation between quantity of endothelial microparticles (CD144+cells) and echocardiography parameters, mean pretransfusion Hb in last 2 years prior to evaluation and transfusion index.However there was a significant negative correlation between quantity of endothelial microparticles (CD144+cells) & frequency of transfusion.