Background:Phosphatidylserine (PS), a cell membrane phospholipid present in the inner layer of the plasma membrane, is expressed on the surface of red blood cells (RBCs) from individuals with congenital and acquired hemoglobinopathies including sickle cell disease (SCD) and thalassemia. These cells are involved in the genesis of several pathobiologic processes including perturbed hemostasis. Based on the amount of cell surface PS, Yasin et al (Blood, 2003) have grouped PS+RBCs into low level PS type-1 (PS1) and high level PS type-2 (PS2) cells. In SCD, the majority of transferrin receptor-positive (CD71+) stress reticulocytes (retics) are PS1+, whereas the majority of PS+dense cells are PS2+and are specific to SCD. PS exposure on retics in subjects with Hemoglobinopathies appears to be physiologically relevant and may play a role in retic maturation. In contrast, dense cells may play a role in the pathogenesis of several SCD-related complications including skin ulcers, pulmonary hypertension and renal disease.