This research will determine if red blood cell (RBC) units from iron-deficient volunteer blood donors fail to meet U.S. Food and Drug Administration (FDA) standards for 24-hour post-transfusion recovery. Over 15 million RBC units are donated annually in the United States. Despite fulfilling all requirements for blood donation, almost two- thirds of the women, and half of the men, who are regular blood donors are iron deficient. RBCs from iron- deficient donors may be specifically damaged by refrigerated storage, thus decreasing their post-transfusion recovery and lifespan in circulation. Our overarching hypothesis is that a substantial proportion of RBC units from iron-deficient volunteer donors are suboptimal. To this end, we propose a prospective, double-blind, randomized, placebo-controlled study of iron-deficient, regular blood donors.
In Aim #1, we will determine whether RBCs from iron-deficient blood donors meet the FDA standards for 24-hour post-transfusion recovery.
In Aim #2, we will determine whether intravenous iron repletion improves the 24-hour recovery of a second, similarly stored, autologous RBC unit. This project will fill critical gaps in knowledge by (i) identifying an unrecognized source of impaired RBC recovery in standard products, (ii) identifying an innovative way to identify donors whose RBC units have impaired tolerance for refrigerated storage using RBC zinc protoporphyrin levels, and (iii) developing a clinical strategy to avoid these adverse effects through iron repletion. This new information will help identify ways to improve the safety and efficacy of RBC transfusions. For example, RBCs that do not circulate cannot deliver oxygen. Thus, measures to improve post-transfusion RBC recovery could lead to sustained improvements in patient outcomes, particularly in those requiring chronic transfusion, where long-term circulation of the maximal number of transfused RBCs is vital, such as patients with sickle-cell disease and ?-thalassemia.

Public Health Relevance

This project will examine the effect of donor iron deficiency on blood transfusion safety. Using a randomized, double-blind, placebo-controlled study design, we will determine whether red cells collected from iron deficient donors meet the Food and Drug Administration approval criteria for clinical use. Furthermore, we will determine whether iron repletion improves the quality of donated red cells. This new information will help identify ways to improve the safety and efficacy of red cell transfusion, especially in those where long-term circulation of the maximal number of transfused red cells is vital, such as patients with sickle-cell disease and ?-thalassemia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL133049-02
Application #
9327056
Study Section
Special Emphasis Panel (ZRG1-VH-D (55)R)
Program Officer
Zou, Shimian
Project Start
2016-08-15
Project End
2021-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
2
Fiscal Year
2017
Total Cost
$761,564
Indirect Cost
$264,608
Name
Columbia University (N.Y.)
Department
Pathology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Youssef, Lyla A; Rebbaa, Abdelhadi; Pampou, Sergey et al. (2018) Increased erythrophagocytosis induces ferroptosis in red pulp macrophages in a mouse model of transfusion. Blood 131:2581-2593
Youssef, Lyla A; Spitalnik, Steven L (2017) Transfusion-related immunomodulation: a reappraisal. Curr Opin Hematol 24:551-557
Youssef, Lyla A; Spitalnik, Steven L (2017) Iron: a double-edged sword. Transfusion 57:2293-2297