Duration of Red Blood Cell Storage Prior to Transfusion

Duration of Red Blood Cell Storage Prior to Transfusion and Non-Transferrin-Bound Iron

This study will determine the minimal duration of red blood cell (RBC) storage that leads to increases in circulating non-transferrin-bound iron in healthy human volunteers post-transfusion. The results from this study will help guide national guidelines for appropriate duration of RBC storage prior to transfusion, which is currently 6 weeks by Food and Drug Administration (FDA) criteria. The overall objective of this research is to improve the safety of refrigerated storage of red blood cells before transfusion.

Study Overview

• Status: Completed
• Conditions: Iron, Blood Level Abnormal
• Intervention / Treatment: Procedure: Blood Transfusion; Other: Packed red blood cells

Detailed Description

Recent studies suggest that older stored blood is associated with worse outcomes in certain hospitalized patients. Red cells may be stored in a refrigerator prior to transfusion for up to 42 days by current FDA standards. Refrigerator storage of red cells is associated with a storage lesion and the survival of transfused red cells decreases with increasing storage time, thus older blood is associated with an increased delivery of hemoglobin-iron to certain parts of the body. The investigators have preliminary data in mice and humans suggesting that delivery of a significant iron load from aged red cells leads to the production of a potentially toxic form of circulating iron called non-transferrin-bound iron.

In this prospective study of healthy volunteers, each subject will be randomized to receive transfusion of one RBC unit after 1, 2, 3, 4, 5, or 6 weeks of storage. The primary outcome will be the 24 hr area under the curve (AUC) of the serum non-transferrin bound iron concentration calculated from samples collected at 0, 2, 4, 6, 8, 10, 12, 14 and 24 hours after transfusion.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-65 years old
• Body weight >110 lbs
• Hemoglobin >12.5 g/dL

Exclusion Criteria:

• Ineligible for donation based on the New York Blood Center blood donor questionnaire
• Systolic blood pressure >180 or <90 mm Hg, diastolic blood pressure >100 or <50 mm Hg
• Heart rate <50 or >100
• Temperature >99.5 F prior to donation
• Temperature >100.4 F or subjective feeling of illness prior to transfusion (this is to avoid having a concurrent illness affect post-transfusion measurements);
• Positive results on standard blood donor infectious disease testing
• Positive urine pregnancy test

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transfusion of PRBC stored for 1 week; Subjects will receive blood transfusion with packed red blood cells stored for 1 week.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC
Experimental: Transfusion of PRBC stored for 2 weeks; Subjects will receive blood transfusion with packed red blood cells stored for 2 weeks.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC
Experimental: Transfusion of PRBC stored for 3 weeks; Subjects will receive blood transfusion with packed red blood cells stored for 3 weeks.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC
Experimental: Transfusion of PRBC stored for 4 weeks; Subjects will receive blood transfusion with packed red blood cells stored for 4 weeks.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC
Experimental: Transfusion of PRBC stored for 5 weeks; Subjects will receive blood transfusion with packed red blood cells stored for 5 weeks.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC
Experimental: Transfusion of PRBC stored for 6 weeks; Subjects will receive blood transfusion with packed red blood cells stored for 6 weeks.	Procedure: Blood Transfusion; A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.; Other Names: Red blood cell (RBC) transfusion; Other: Packed red blood cells; Red blood cells that have been collected, processed, and stored in bags as blood product units available for blood transfusion. A standard autologous leukoreduced packed red blood cell unit will be collected and stored in AS-3 solution in the Columbia University Medical Center blood bank. The number of weeks in storage are as follows: 1 week; 2 weeks; 3 weeks; 4 weeks; 5 weeks; 6 weeks; Other Names: PRBC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-transferrin-bound Iron Level (AUC)	Area under the curve of change of Non-transferrin-bound iron from immediately after transfusion to end of observation (i.e., from 0-hr after transfusion to 24-hr after transfusion).	0, 2, 4, 6, 8, 10, 12, 14 and 24 after transfusion

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Steven L Spitalnik, MD, Columbia University

Publications and helpful links

General Publications

• Rapido F, Brittenham GM, Bandyopadhyay S, La Carpia F, L'Acqua C, McMahon DJ, Rebbaa A, Wojczyk BS, Netterwald J, Wang H, Schwartz J, Eisenberger A, Soffing M, Yeh R, Divgi C, Ginzburg YZ, Shaz BH, Sheth S, Francis RO, Spitalnik SL, Hod EA. Prolonged red cell storage before transfusion increases extravascular hemolysis. J Clin Invest. 2017 Jan 3;127(1):375-382. doi: 10.1172/JCI90837. Epub 2016 Dec 12.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Blood Transfusion; Iron; Red Blood Cells
• Other Study ID Numbers: AAAI0835; R01HL115557 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No