Fifty to seven-five percent of RBC components from donors with sickle cell trait occlude leukocyte reduction filters. People with sickle cell trait are healthy, but very low oxygen levels, low pH, and high hemoglobin concentrations can induce RBC intracellular hemoglobin S polymerization. We have found that hemoglobin S polymerization due to low oxygen tension in venous blood and low ph and high osmolarity of the citrate anticoagulant is responsible for the failure of RBC components from donors with sickle cell trait to filter. The goal of these studies is to develop a practical method to allow the successful leukocyte reduction by filtration of all RBC components collect from donor with sickle cell trait. The method should be easy to use in conjunction with existing blood collection technologies. The purpose of ongoing studies is to determine if the failure of sickle cell trait donor blood to filter can be avoided by improving the oxygenation of blood prior to filtration. Since adding 60 mL of air effectively increased oxygen levels, units of blood from 10 sickle cell trait donors were divided into two and one half was placed into a bag with 60 mL of air and the other into a bag without air. Both halves were incubated for 2 hours. RBC components were prepared and passed through leukocyte reduction filters. We found that when sickle trait donor blood (n=10) was incubated with 60 mL of air, 9 of 10 components filtered completely. Only 1 of 9 components incubated without air filtered completely. These studies show that RBC components from sickle cell trait donors can be successfully filtered when oxygen levels are increased. Current studies are focused on developing a method to increase oxygen levels it stored blood that is suitable for use with blood that will be transfused.