Physiologic Effects of RBC Storage in Chronic Transfusion Recipients: Vasoreactivity, Exercise Capacity, and Oxygen Consumption
Trial Snapshot
- Phase
- Phase 4
- Status
- Terminated
- Sponsor
- Emory University
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Change in Reactive Hyperemic Index (RHI)
Study Overview
Brief Summary
The purpose of this study is to determine how red blood cell transfusions, particularly the length of storage time of units of packed red blood cells, affects the cardiovascular function in patients receiving transfusions. This study will also determine the most ideal way of storing and processing blood, and assess how transfusion affects a person's ability to exercise and how their blood vessels relax and contract.
Detailed Description
The purpose of this study is determine red blood cell transfusion, particularly the length of storage time of units of packed red blood cells, affects cardiovascular function in patients receiving transfusions. Transfusion of red blood cells is often used clinically in patients with low red blood cell counts in order to prevent disease progression and death. Recent studies suggest that the use of "aged" versus "fresh" red blood cells is associated with worse clinical outcomes, but there is no clear understanding on how this happens. The investigators want to determine the most ideal way of storing and processing blood, and learn how transfusion affects the ability to exercise in the study subjects and assess the relaxation and contraction of the blood vessels.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Eligibility Criteria
- Ages
- 21 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •- Subjects with any condition resulting in transfusion-dependent anemia
Exclusion Criteria
- •Age <21 or >80 years
- •Pregnancy
- •Acute infection in previous 4 weeks
- •Active substance abuse within the past year
- •Inability to give informed consent
- •Inability to return for follow-up
- •The presence of alloantibodies that would limit the blood bank's ability to obtain correctly aged red blood cell (RBC) units
Arms & Interventions
Fresh RBC transfusion/Storage-aged RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (<10 days old) followed by a transfusion of packed RBC units of storage-aged (>21 days old) blood.
Intervention: Fresh red blood cell (RBC) transfusion (Biological)
Fresh RBC transfusion/Storage-aged RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (<10 days old) followed by a transfusion of packed RBC units of storage-aged (>21 days old) blood.
Intervention: Storage-aged red blood cell (RBC) transfusion (Biological)
Fresh RBC transfusion/Storage-aged RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of fresh blood (<10 days old) followed by a transfusion of packed RBC units of storage-aged (>21 days old) blood.
Intervention: Electronic infusion pump (Device)
Storage-aged RBC transfusion/Fresh RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (<10 days old).
Intervention: Fresh red blood cell (RBC) transfusion (Biological)
Storage-aged RBC transfusion/Fresh RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (<10 days old).
Intervention: Storage-aged red blood cell (RBC) transfusion (Biological)
Storage-aged RBC transfusion/Fresh RBC transfusion
Subjects will receive a transfusion of packed red blood cell (RBC) units of storage-aged (>21 days old) blood followed by a transfusion of packed RBC units of fresh blood (<10 days old).
Intervention: Electronic infusion pump (Device)
Outcomes
Primary Outcomes
Change in Reactive Hyperemic Index (RHI)
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Reactive Hyperemia Index (RHI) will be measured using Pulsatile Arterial Tonometry (PAT). Baseline blood pressure of both hands is measured and PAT probes are placed one on each hand at the same finger (fingers 2, 3 or 4). Following an equilibration period of 10 minutes, the blood pressure cuff will be inflated to 60 mmHg above systolic pressure for 5 minutes followed by deflation of the cuff and the pulsatile recordings from both study and control fingers will be measured. RHI will be calculated from the ratio of the digital pulse volume during reactive hyperemia (following cuff deflation) and baseline. A higher RHI indicates better nitric oxide-dependent endothelial function.
Change in Flow-mediated Vasodilation (FMD)
Time Frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Brachial artery flow-mediated dilation (FMD) will be performed by using ultrasonography. The brachial artery of the non-dominant arm will be imaged using a high-resolution 13 MHz ultrasound transducer. A blood pressure cuff on the forearm will be inflated to supra-systolic pressures to produce 5 minutes of ischemia. After cuff deflation, imaging of the brachial artery will be performed continuously for the next 120 seconds and the flow-mediated dilation will be calculated. Change in FMD is the percent change in the diameter of the brachial artery from baseline (prior to transfusion) to Day 1 (first post-transfusion day). A higher FMD indicates better nitric oxide-dependent endothelial function.
Secondary Outcomes
- Respiratory Exchange Ratio (RER):(Day 1 (first post-transfusion day))
- Peak VO2 Lean(Day 1 (first post-transfusion day))
- Maximal Oxygen Uptake (VO2Max)(Day 1 (first post-transfusion day))
- O2 Pulse(Day 1 (first post-transfusion day))
- Change in Oxidative Stress Markers(Baseline (prior to transfusion), Day 1 (first post-transfusion day))
- Change in Levels of IL-6(Baseline (prior to transfusion), Day 1 (first post-transfusion day))
- Change in Levels of IL-2(Baseline (prior to transfusion), Day 1 (first post-transfusion day))
- Change in Levels of Nitric Oxide Metabolites(Baseline (prior to transfusion), Day 1 (first post-transfusion day))
- Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP(Baseline (prior to transfusion), Day 1 (first post-transfusion day))
Investigators
Arshed A. Quyyumi
Professor
Emory University