Activation of endothelial cell, coagulation and fibrinolysis in children with beta- and alpha-thalassemia

Abstract

Introduction : Thromboembolic complications due to hypercoagulable states are common in thalassemic patients, mostly adults. The change in the endothelial cell from resting to procoagulant state could be associated with expression of adhesion molecules and selectins. Subsequently, endothelial cell injury can alter hemostasis by promoting fibrin-clot formation.

Objective : To determine plasma levels of endothelial, coagulation and fibrinolysis markers (soluble intercellular adhesion molecules (sICAM-1), vascular endothelial growth factor (VEGF), soluble endothelial selectin (sESelectin), factor VIII activity (FVIII: C) and D-dimer) in children with thalassemia.

Design/Methods : This is a cross sectional study. Plasma samples from 120 children with thalassemia (30 with non-splenectomized alpha-thalassemia (NSA), 65 with non-splenectomized beta-thalassemia major (NSB) and 25 with splenectomized beta-thalassemia major (SB) aged 1 to 16 years old were assayed for sICAM-1, VEGF, sE-Selectin, FVIII:C and D-dimer, whereas samples from thirty-five healthy children served as controls.

Results : Plasma levels of sICAM-1 were significantly elevated in patients with NSA, NSB and SB compared to controls (324.7 ± 83.9; p 0.001, 277.5 ± 99.6; p 0.001and 422.3 ± 128.9; p 0.001 vs. 150.9 ± 41.9 ng/ml, respectively). Plasma E-selectin levels were significantly increased in NSA and SB versus controls (60.4 ± 32.8; p = 0.008, 63.9 ± 34.2; p = 0.003 vs. 39.5 ± 11.3 ng/ml, respectively). Plasma VEGF levels were elevated; however, the statistical difference was not significant. Plasma D-dimer levels were significantly increased in SB versus controls (365.5 ± 200 vs. 200.6 ± 54.1 ng/ml; p = 0.02, respectively). On the contrary, FVIII: C levels were significantly decreased in NSA and NSB versus controls (57.8 ± 13.5; p 0.001, 67.4 ± 23.9; p 0.001 vs. 96.7 ± 27.7 ng/ml, respectively). Comparing NSB to SB patients, SB patients had significantly higher plasma concentrations of sICAM-1, E-selectin and D-dimer than NSB patients (p 0.001, p = 0.003 and p = 0.005, respectively).

Conclusion : There is evidence of endothelial cell activation and alteration of coagulation and fibrinolysis in children with thalassemia which increases the risk of thromboembolic complications.