Induction of impaired membrane phospholipid asymmetry in mature erythrocytes after chemotherapy.

Senescent erythrocytes undergo a loss of phospholipid asymmetry in the plasma membrane and are removed from the circulation by phagocytosis.To examine the loss of phospholipid asymmetry in mature erythrocytes after chemotherapy, we monitored phosphatidylserine (PS)-exposing erythrocytes by using flow cytometry to detect annexin V-bound erythrocytes in the circulation of acute lymphoblastic leukemia patients after consolidation chemotherapy. Both the percentage and the absolute number of annexin V-positive erythrocytes gradually increased immediately after chemotherapy. This result paralleled the change in the serum levels of bilirubin, suggesting a direct induction of PS-externalization in mature erythrocytes and a subsequent increase in erythrocyte clearance by splenic macrophages. The PS-exposing erythrocyte counts showed negative correlations to platelet and reticulocyte counts, which reflect the hematopoietic potential in the bone marrow. This result suggests that bone marrow suppression could be responsible for the enlarged senescent population in the circulation. Moreover, PS-exposing erythrocytes in the circulation remained at relatively high levels even after the serum level of bilirubin normalized, indicating that the decreased clearance of senescent erythrocytes as a result of impaired phagocytosis following bone marrow suppression might also be involved in the increase in PS-exposing erythrocytes in the circulation late after chemotherapy.