MEMBRANE PHOSPHOLIPID ASYMMETRY IN HUMAN THALASSEMIA

Phospholipid asymmetry in the red blood cell (RBC) lipid bilayer is we ll maintained during the life of the cell, with phosphatidylserine (PS ) virtually exclusively located in the inner monolayer. Loss of phosph olipid asymmetry, and consequently exposure of PS, is thought to play an important role in red cell pathology. The anemia in the human thala ssemias is caused by a combination of ineffective erythropoiesis (intr amedullary hemolysis) and a decreased survival of adult RBCs in the pe ripheral blood. This premature destruction of the thalassemic RBC coul d in part be due to a loss of phospholipid asymmetry, because cells th at expose PS are recognized and removed by macrophages. In addition, P S exposure can play a role in the hypercoagulable state reported to ex ist in severe beta-thalassemia intermedia. We describe PS exposure in RBCs of 56 comparably anemic patients with different genetic backgroun ds of the alpha- or beta-thalassemia phenotype. The use of fluorescent ly labeled annexin V allowed us to determine loss of phospholipid asym metry in individual cells. Our data indicate that in a number of thala ssemic patients, subpopulations of red cells circulate that expose PS on their outer surface. The number of such cells can vary dramatically from patient to patient, from as low as that found in normal controls (less than 0.2%) up to 20%. Analysis by fluorescent microscopy of bet a-thalassemic RBCs indicates that PS on the outer leaflet is distribut ed either over the entire membrane or localized in areas possibly rela ted to regions rich in membrane-bound alpha-globin chains. We hypothes ize that these membrane sites in which iron carrying globin chains acc umulate and cause oxidative damage, could be important in the loss of membrane lipid organization. In conclusion, we report the presence of PS-exposing subpopulations of thalassemic RBC that are most likely phy siologically important, because they could provide a surface for enhan cing hemostasis as recently reported, and because such exposure may me diate the rapid removal of these RBCs from the circulation, thereby co ntributing to the anemia. (C) 1998 by The American Society of Hematolo gy.