Although people who are homozygous for sickle hemoglobin, hemoglobin S, have a serious disease, sickle cell anemia, people with sickle cell trait who are heterozygous for hemoglobin S are healthy and make excellent blood donors. However, blood from patients with sickle cell trait often occludes filters that remove leukocytes from red blood cell components intended for transfusion. Since most hospitals only transfuse red blood cells that have been filtered to remove red blood cells, people with sickle cell trait can no longer donate red blood cells. These studies investigated the causes and prevention of the occlusion of leukocyte reduction filters by blood from patients with sickle cell trait. While at physiological conditions, hemoglobin S in red blood cells (RBCs) from patients with sickle cell trait does not polymerize, at very low oxygen levels, low pH, and high hemoglobin concentrations hemoglobin S in RBCs from people with sickle cell trait can polymerize. 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 used for blood collection is responsible for the failure of RBC components from donors with sickle cell trait to filter. RBCs with polymerized hemoglobin S become stiff and viscous and are unable to pass through leukocyte reduction filters. We found that increasing the oxygen tension in RBC components collected from donors with sickle cell trait allowed their RBCs be pass through leukocyte reduction filters. When hemoglobin oxygen saturations increased to greater than 60% RBC components from donors with sickle cell trait filtered effectively. We tested the effects of bag type and size on the oxygenation of stored red blood cells. We found that standard sized bags made from plastics that were approved for the storage of red cells for transfusion did not transfer enough oxygen to allow sufficient increases in hemoglobin oxygen saturation to allow effective filtration. We are currently investigating the effects of an alternate method of blood collection on hemoglobin S polymerization and the filterability of RBC components from patients with hemoglobin S. Sickle trait RBC components collected with a device that automatically added small quantities of citrate anticoagulant to the blood as it was collected allowed the sickle trait blood to more effectively pass through the leukocyte reduction filters then control units collected using standard methods. However, many red cell components collected with the automated system did not meet the required standards for removal of leukocytes and recovery of RBC. Future studies will assess the effects of modifying the automated collection device to add less citrate anticoagulant to the collected blood.