There is a great deal of clinical variability in patients with sickle cell disease. Although alpha thalassemia and fetal hemoglobin levels have been identified as important factors in regard to clinical severity, the clinical course in many patients can not be explained based upon these two parameters and additional factors must be sought. Our hypothesis is that careful evaluation of cellular and membrane parameters such as deformability, density profile and adherence to endothelial cells in patients who are simultaneously being evaluated for clinical problems related to sickle cell disease, may provide new insights into the relationship between membrane or cellular abnormalities and the pathophysiology of sickle cell disease. We have included this core facility in our center application so that we can add specific biophysical measurements to our clinical and basic research projects and enhance the information we will derive from these projects. An established cell biology-biophysical facility will be used to investigate cell deformability by ektacytometry of ghosts and intact red blood cells, density profiles on a prototype Technicon H-1 and red cell-endothelial cell adherence using a newly developed, clinically applicable method. When significant abnormalities are detected in either deformability or adherence, further evaluation of these cells, or the plasma in which these cells were suspended, will be undertaken. For these measurements, a micropipette assay will be used to characterize the defects in cell deformation or to characterize the abnormalities in adherence and analysis will be done on whole blood as well as density fractionated red cells. The clinical projects which this core facility will be most helpful in are 1.) drug trials with hydroxyurea or butyric acid in children and adults, 2.) acute chest syndrome patients at baseline and throughout their clinical course, 3.) patients in the central nervous system study, 4.) children followed during the first three years of life, 5.) patients who have severe clinical manifestations compared to patients who have mild disease, 6.) and patients who have undergone bone marrow transplantation. The studies in patients treated with hydroxyurea will be of particular interest as their red cells are known to have a dramatic increase in MCV and careful characterization of the membrane/cellular properties of these cells has not been performed. By comparing the results we obtain in the cell biology core to the clinical course of patients under study, we hope to establish the relative importance of these cellular changes to the pathophysiology of sickle cell disease.
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