Endothelial dysfunction in Sickle Cell Disease and Thalassemia Intermedia

Haema 2011; 2(2): 262-271

by Ino Kanavaki1, Ioannis Rombos2, Ioannis Papassotiriou3

1Service de Pédiatrie, Département de l’ Enfant et de l’ Adolescent, Hôpitaux Universitaires de Genève, Switcherland, 2First Department of Internal Medicine, Athens University Medical School, Athens, 3Department of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, Athens Greece

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Abstract

The vascular endothelium is implicated in the pathophysiology of many diseases by producing and expressing a variety of molecules and factors. Endothelial cell activation is a complicated series of reactions which can occur both in health and in disease. One of these situations is where the endothelium is highly activated even in steady state conditions and results in the increased expression of soluble endothelial adhesion molecules, such as sICAM-1 and sVCAM-1, P and Ε selectin and thrombomodulin. This increase reflects the endothelial damage present in these patients. The damage is somehow reversed by hydroxyuria and adhesion molecules levels decrease in patients under hydroxyuria treatment. Chronic inflammation is also an important element in the pathophysiology of Sickle Cell Disease and this explains the high levels of inflammation markers such as CRP found in these patients even in steady state. Endothelial cell activation seems to be also implicated in the pathophysiology of Thalassemia Intermedia, however there are few relevant studies. Endothelial activation is expressed through the increase of serum levels if endothelial adhesion molecules such as sICAM-1 s and sVCAM-1, Ε selectin, von Willebrand factor and thrombomodulin. Furthermore, these patients present chronic inflammation and this is reflected by the increased CRP levels. Therapeutic interventions such as hydroxyuria treatment and splenectomy do not seem to influence adhesion molecules’ levels. In conclusion vascular endothelium plays a major role in the pathophysiology of Sickle Celle Disease and Thalassemia Intermedia. Endothelial activation can explain the origin of vasoocclusive crises as well as the complications seen in Sickle Cell patients. In Thalassemia Intermedia studies show an important degree of endothelial damage present in this otherwise “benign” clinical condition.