Adverse Effects of RBC Transfusions: A Unifying Hypothesis (INOBA)
Transfusion of red blood cells is often used in critically ill patients with low red blood cell counts to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells are associated with worse clinical outcomes. There is evidence that red blood cells work with the cells lining our blood vessels to produce a variety of substances that normally cause arteries to relax and increase blood supply. Two of these substances are called nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). We are trying to determine the nature of these substances in human beings when they are transfused "aged" versus "fresh" red blood cells. It is our thought that "aged" red blood cells have less of the substances (NO and EDHF) that naturally relax our arteries and further changes the blood supply. One way to determine this is to transfuse a subject's own "aged" and "fresh" red blood cells and inject substances such as L-NMMA (L-NG monomethyl arginine) and TEA (tetraethylammonium chloride), which block the production of NO and EDHF respectively, and then, study what happens to the blood flow. This study is also designed to test the effects of transfusing "aged" versus "fresh" red blood cells in volunteers with traditional cardiovascular risk factors (high blood pressure, diabetes, high cholesterol, and tobacco use) on 1) the degree of relaxation in the arteries and subsequent changes in blood flow, 2) blood levels of oxidant molecules, 3) inflammation, and 4) stem cells.
There is evidence that red blood cells produce NO, which normally causes arteries to relax and increase blood supply. We will try to determine the nature of NO in red blood cells and whether the amount of this substance is altered because of different blood processing and storage techniques. It is our thought that "aged" red blood cells have less NO that naturally relaxes our arteries and further changes the blood supply. This study is designed to determine the most ideal way of storing and processing blood.
Biological: Fresh blood
Biological: Aged blood
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Adverse Effects of RBC Transfusions: A Unifying Hypothesis|
- To investigate the effects of blood processing and storage (using standard FDA-approved conditions) on NO production and scavenging by human RBCs/Hb in vitro. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- To transfuse healthy volunteers and investigate the effects of storage-related RBC changes on blood flow, tissue oxygenation, and biomarkers of cardiovascular function. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
- To determine the effects of transfused RBCs in patients with endothelial dysfunction due to cardiovascular disease. [ Time Frame: 4 years ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Estimated Study Completion Date:||October 2013|
|Estimated Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
|Experimental: Fresh blood||
Biological: Fresh blood
For fresh transfusions, a whole blood unit will be drawn from volunteers, processed, and then reinfused on the same day during the study. For impaired and repaired transfusions, the volunteers will be brought to the blood bank to donate; then, after processing and the appropriate length of storage (eg, 28 days), they will return for the FBF studies. Since recipients of fresh transfusions are relatively anemic after donation and before reinfusion, recipients of impaired/repaired transfusions should also be mildly anemic for the study. Thus, they will donate another whole blood unit prior to beginning the study course, they will be transfused with their stored unit during the study, and then the autologous unit collected at the beginning of the day will be reinfused at the end of the day after the study is complete.
|Experimental: Aged blood||
Biological: Aged blood
In a separate aim, the FMD assay will be used to investigate NO-mediated vasodilation in patients with CVD who are receiving transfusions. Over 60% of blood orders for cardiology patients at Emory are for 2 units or more. Therefore, when a 2-unit order is placed on a consented patient, they will be issued both fresh (< 7 days) and impaired (> 28 days) compatible units from inventory. Prior to starting transfusions, the patient will be randomized to either receive the fresh or the older unit first. All RBC units will be ACD/AS1. Units will also be leukoreduced and/or irradiated, if either of those modifications were found to impair NO bioavailability in prior studies. If washing or rejuvenation were found to be successful in significantly "repairing" NO bioavailability in previous aims, some patients may also receive impaired and repaired (> 28 days; washed or rejuvenated) RBC transfusions.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT00838331
|United States, Georgia|
|Atlanta, Georgia, United States|
|Principal Investigator:||Arshed A Quyyumi, MD||Emory University|
|Principal Investigator:||John Roback, MD, PhD||Emory University|