648 TRANSFUSION OF YOUNG RBCs WITH IMPROVED SURVIVAL: A NEW APPROACH TO THE THERAPY OF COOLEY'S ANEMIA

Abstract

In Cooley's anemia, maintenance of a mean Hgb level of 12g improves quality of life and prevents cardiac dysfunction. The resulting Fe overload (FO), which ultimately leads to death, could be reduced by transfusion of RBCs with improved survival. Age-dependent separation of RBCs can be obtained by buoyant density centrifugation on isotonic solutions of arabinogalactane (AG). Rabbit RBCs were divided into 2 equal parts: light-young (LY) and heavy-old (HO) RBCs, by centrifugation through a single layer of AG. LY-RBCs, HO-RBCs, mixtures of the two and unfractionated RBCs were washed, labelled with 51Cr and reinfused into the donors. RBCs survival was corrected for 51Cr elution and random cell loss by an appropriate mathematical model. Mean survival (MS) of LY-RBCs was 28d; for HO-RBCs, 14d; for both and unfractionated RBCs, 19d, indicating excellent age-dependent separation.(AG toxicity was negligible: LD50 in mice > 10g; AG antigenicity was undetectable in guinea pigs.) These results indicate that human LY-RBCs with MS of 88d (vs 60d in unfractionated RBCs) can be prepared. A mean Hgb of 12g can be maintained by transfusion of LY-RBCs, with less fluctuation and with only 2/3 of the Fe. This avoids transfusion of HO-RBCs that contribute as much to FO as LY-RBCs, yet offer the patient short and inefficient oxygen transport. Combination of improved transfusion modality with modern chelation therapy may lead to Fe balance in Cooley's anemia, which ultimately may permit prolonged survival.