Iron, Blood Level Abnormal
Conditions
Keywords
Blood Transfusion, Iron, Red Blood Cells
Brief summary
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.
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.
Interventions
PROCEDUREBlood Transfusion
A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Columbia University
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Non-transferrin-bound Iron Level (AUC) | 0, 2, 4, 6, 8, 10, 12, 14 and 24 after transfusion | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Transfusion of PRBC Stored for 1 Week Subjects will receive blood transfusion with packed red blood cells stored for 1 week.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 8 |
| Transfusion of PRBC Stored for 2 Weeks Subjects will receive blood transfusion with packed red blood cells stored for 2 weeks.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 10 |
| Transfusion of PRBC Stored for 3 Weeks Subjects will receive blood transfusion with packed red blood cells stored for 3 weeks.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 7 |
| Transfusion of PRBC Stored for 4 Weeks Subjects will receive blood transfusion with packed red blood cells stored for 4 weeks.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 8 |
| Transfusion of PRBC Stored for 5 Weeks Subjects will receive blood transfusion with packed red blood cells stored for 5 weeks.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 10 |
| Transfusion of PRBC Stored for 6 Weeks Subjects will receive blood transfusion with packed red blood cells stored for 6 weeks.
Blood Transfusion: A routine medical procedure in which blood is given through an intravenous (IV) line a blood vessel.
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 | 9 |
| Total | 52 |
Baseline characteristics
| Characteristic | Transfusion of PRBC Stored for 1 Week | Total | Transfusion of PRBC Stored for 6 Weeks | Transfusion of PRBC Stored for 5 Weeks | Transfusion of PRBC Stored for 4 Weeks | Transfusion of PRBC Stored for 3 Weeks | Transfusion of PRBC Stored for 2 Weeks |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 25 years | 27 years | 26 years | 28 years | 28 years | 28 years | 25 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 11 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 41 Participants | 8 Participants | 9 Participants | 5 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 11 Participants | 3 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 32 Participants | 5 Participants | 5 Participants | 5 Participants | 4 Participants | 7 Participants |
| Region of Enrollment United States | 8 participants | 52 participants | 9 participants | 10 participants | 8 participants | 7 participants | 10 participants |
| Sex: Female, Male Female | 2 Participants | 20 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 32 Participants | 6 Participants | 6 Participants | 5 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 10 | 0 / 7 | 0 / 8 | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 0 / 8 | 0 / 10 | 0 / 7 | 0 / 8 | 0 / 10 | 0 / 9 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 | 0 / 7 | 0 / 8 | 0 / 10 | 0 / 9 |
Outcome results
Primary
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).
Time frame: 0, 2, 4, 6, 8, 10, 12, 14 and 24 after transfusion
Population: 52 out of the 60 enrolled subjects completed the study and were included in data analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Transfusion of PRBC Stored for 1 Week | Non-transferrin-bound Iron Level (AUC) | 0.5588 microMole*hr/L |
| Transfusion of PRBC Stored for 2 Weeks | Non-transferrin-bound Iron Level (AUC) | 2.839 microMole*hr/L |
| Transfusion of PRBC Stored for 3 Weeks | Non-transferrin-bound Iron Level (AUC) | 3.684 microMole*hr/L |
| Transfusion of PRBC Stored for 4 Weeks | Non-transferrin-bound Iron Level (AUC) | 5.272 microMole*hr/L |
| Transfusion of PRBC Stored for 5 Weeks | Non-transferrin-bound Iron Level (AUC) | 6.416 microMole*hr/L |
| Transfusion of PRBC Stored for 6 Weeks | Non-transferrin-bound Iron Level (AUC) | 39.24 microMole*hr/L |