Pulmonary hypertension in thalassemic children: does endothelial dysfunction play a role?

ABSTRACT

The thalassemia syndromes are a heterogeneous group of inherited hemoglobin disorders resulting from impaired production of either the alpha or beta globin chain subunits of the hemoglobin tetramer. Heart failure is the most common cause of death in thalassemia. Thalassemic heart disease involves mainly left ventricular dysfunction caused by transfusion- induced iron overload. However, recent studies suggest that TM patients have a unique hemodynamic pattern consistent with right ventricular cardiomyopathy, and pulmonary hypertension in addition to the LV abnormalities. Pulmonary hypertension in beta-thalassemia could represent a common, yet less well-explored complication in the cardiopulmonary spectrum of the disease. The aim of this study is to determine serum levels of cholesterol, triglycerides, nitric oxide [NO], endothelin-1 [ET-1], lnterlukin-6 [lL-6] and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intercellular adhesion molecule [sICAM-1] in transfusion-dependent beta-thalassemia children and to correlate these markers with the echocardiographic findings as well as serum ferritin of these patients. The study included 32 transfusion-dependant children with beta-thalassemia aged 5 to 15 years and 40 apparently healthy children as a control group. Serum levels of cholesterol, triglycerides, NO, ET-1, lL-6 and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intracellular adhesion molecule [sICAM-1] were determined for patients and controls. In addition echocardiography was also done. Serum levels of ET-1, lL-6 and the soluble forms of vascular cell adhesion molecule [sVCAM-1] as well as intracellular adhesion molecule [sICAM-1] were significantly higher in the studied cases than the controls while serum levels of cholesterol and NO were significantly lower. Echocardiographic evidence of pulmonary hypertension was detected in 68.75% of the cases. The lassemic cases with PHT had significantly higher values of ET-1, lL-6, VEGF, sICAM and sVCAM than those without PHT. Pulmonary hypertension in beta-thalassemia could be an additional complication in the cardiopulmonary spectrum of the disease due to NO deficiency as a result of iron overload and endothelial dysfunction. Therapeutic interventions that decrease hemolytic rate, improve, enhance NO effects, or act as NO donors are of potential benefit and may alter the progression of the disorder