The primary goal of Project 1 is to improve red blood cell (RBC) transfusion practices for anemic,[unreadable] critically ill infants, a high-risk patient group given multiple RBC transfusions. The newborn infant and[unreadable] lamb studies proposed are timely because they address substantive unresolved issues in neonatal[unreadable] RBC transfusion practices, e.g., use of 21-42 d stored adult allogeneic RBCs (vs. exclusive use of fresh[unreadable] RBCs <7 d) and use of autologous placental RBCs, potentially a safer option made feasible by point-ofcare[unreadable] testing devices. Our proposal extends our previous PPG's work by considering for the first time in[unreadable] infants the effect of storage on RBC post-transfusion recovery and survival, taking into account unique[unreadable] and critical factors that perturb, thereby confounding, RBC survival measurements. Project 1's overall[unreadable] hypothesis is that post-transfusion survival of allogeneic and autologous erythrocytes can be accurately[unreadable] quantified in anemic human infants using a newborn lamb model based on biotin-labeled RBCs[unreadable] combined with mathematical modeling to compensate for confounding variables commonly[unreadable] encountered in the early newborn period (e.g., RBC loss due to phlebotomy, RBC gain due to[unreadable] transfusion, and RBC dilution due to erythropoiesis both in response to anemia and to increased blood[unreadable] volume with rapid growth). Clinically useful RBC recovery and survival parameters, which we refer to as[unreadable] "RBC kinetics" (i.e., short-term post-transfusion recovery at 24 hr ("PTR24") and long-term mean[unreadable] potential life span ("MPL")) will be determined using RBC biotinylation methodologies developed in our[unreadable] previous PPG. Project 1 proposes, in four specific aims, to: 1) develop and validate in adult sheep the[unreadable] ability to biotinylate RBCs at up to 5 discrete densities to determine "RBC kinetics" of multiple RBC[unreadable] populations simultaneously; 2) apply the RBC biotinylation methodology from Aim #1 to measure the[unreadable] effect of stress erythropoiesis on RBC survival in normal adult sheep in steady-state erythropoiesis; 3)[unreadable] utilize in newborn lambs the RBC biotinylation methodology from Aim #1 to develop an ethically[unreadable] acceptable, mathematically accurate model to compensate for the above-noted factors uniquely[unreadable] influencing measurements of posttransfusion RBC Kinetics in critically ill infants; and 4) use the RBC[unreadable] biotinylation and mathematical modeling methodologies validated in Aims #1 and #3 to accurately[unreadable] measure post-transfusion RBC kinetics in anemic newborn infants transfused with fresh autologous,[unreadable] fresh allogeneic and stored allogeneic RBCs. The use of biotin, a non-toxic, non- radioactive B vitamin,[unreadable] to distinguish among different RBC populations simultaneously by flow cytometry is critical for[unreadable] accomplishing Project 1's aims and holds clear advantages over other RBC labeling methods in both[unreadable] safety and accuracy. In utilizing the four Specific Aims to achieve our goal of establishing more effective[unreadable] transfusion practices by identifying the optimal RBC transfusion product for use in anemic infants,[unreadable] Project 1 supports our PPG's themes of investigating the mechanisms and optimizing the management[unreadable] of neonatal anemia.
NIH ExPorter
NIH ExPorter