Abstract: The invention describes improved methods and reagent compositions employed therein to determine the existence of blood disorders such as hemolytic anemias in a blood sample obtained from an individual. The methods are preferably carried out on an automated flow cytometer and encompass determining if the individual's red blood cells have undergone a loss of membrane surface area by providing measurements of the surface area and the sphericity of the red blood cells in a whole blood sample as a function of osmolality. The method and reagent compositions used therein provide for the first time accurate measurements of the surface areas of both the mature red blood cell and the reticulocyte populations in a whole blood sample. The method and reagents of the invention promise to shed new insights into reticulocyte membrane remodeling in various red cell disorders.