Red Blood Cell Transfusion
Conditions
Keywords
Chronic anemia, Cardiopulmonary testing, Transfusion-dependent anemia
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.
Interventions
BIOLOGICALFresh red blood cell (RBC) transfusion
1 or 2 cross-matched, packed red blood cells (RBC) units from fresh (\<10 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit.
BIOLOGICALStorage-aged red blood cell (RBC) transfusion
1 or 2 cross-matched, packed red blood cells (RBC) units from storage-aged (\>21 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit.
DEVICEElectronic infusion pump
A programmable, electronic infusion pump (Baxter, Inc) will be used for intravenous transfusion of units of packed red blood cells (RBC). The pump will be programmed to deliver 1 unit of packed RBC per hour.
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Flow-mediated Vasodilation (FMD) | 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. |
| Change in Reactive Hyperemic Index (RHI) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| O2 Pulse | Day 1 (first post-transfusion day) | Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. O2 (oxygen) pulse is the amount of O2 consumed from the volume of blood delivered to tissues by each heartbeat; this index is calculated as: O2 pulse = VO2 / heart rate. A higher O2 pulse indicates better vascular reactivity. |
| Peak VO2 Lean | Day 1 (first post-transfusion day) | Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Peak VO2 lean is the peak oxygen uptake adjusted for lean body mass and is reported as a lean body weight-adjustment parameter in mL/kg per minute. |
| Change in Oxidative Stress Markers | Baseline (prior to transfusion), Day 1 (first post-transfusion day) | Oxidative stress will be measured using high-performance liquid chromatography (HPLC) to collect plasma cystine, cysteine, glutathione, and glutathione disulfide levels. Higher levels of cystine, cysteine, glutathione, and glutathione disulfide indicate higher levels of vascular inflammation. |
| Maximal Oxygen Uptake (VO2Max) | Day 1 (first post-transfusion day) | Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Maximal oxygen uptake (VO2Max) is the value achieved when the oxygen uptake remains stable despite a progressive increase in the intensity of exercise. The VO2Max will be calculated from the cardiac output and the arteriovenous oxygen difference during peak exercise. VO2Max is expressed in milliliters of oxygen per minute per kilogram of body weight (ml/min/kg). A higher VO2Max indicates better vascular reactivity. |
| Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP | Baseline (prior to transfusion), Day 1 (first post-transfusion day) | Levels of high-sensitivity C-reactive protein (hsCRP) in the blood will be measured by using Dade Behring nephelometry. Higher levels of hsCRP indicate increased vascular inflammation. |
| Change in Levels of IL-6 | Baseline (prior to transfusion), Day 1 (first post-transfusion day) | Plasma IL-6 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-6 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-6 indicate increased vascular inflammation. |
| Change in Levels of IL-2 | Baseline (prior to transfusion), Day 1 (first post-transfusion day) | Plasma IL-2 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-2 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-2 indicate increased vascular inflammation. |
| Change in Levels of Nitric Oxide Metabolites | Baseline (prior to transfusion), Day 1 (first post-transfusion day) | Nitric oxide metabolites like nitrite, nitrate, S-nitrosothiols (SNO-Hb and SNO-thiol) will be measured from blood samples using high-performance liquid chromatography (HPLC). Higher levels of nitric oxide metabolites indicate higher levels of nitric oxide (NO) synthesis and better vascular reactivity. |
| Respiratory Exchange Ratio (RER): | Day 1 (first post-transfusion day) | Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. RER is the ratio of VCO2 (carbon dioxide output) to VO2 (oxygen uptake). A higher RER indicates better vascular reactivity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fresh RBC Transfusion/Storage-aged RBC Transfusion Fresh red blood cell (RBC) transfusion: 1 or 2 cross-matched, packed red blood cells (RBC) units from fresh (\<10 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit. | 9 |
| Storage-aged RBC Transfusion/Fresh RBC Transfusion Storage-aged red blood cell (RBC) transfusion: 1 or 2 cross-matched, packed red blood cells (RBC) units from storage-aged (\>21 days old) blood, as ordered by the attending physician, will be given as an intravenous infusion via a programmable electronic infusion pump (Baxter, Inc) over a period of 1 hour per unit. | 6 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Equipment failure | 1 | 1 |
| Overall Study | Physical limitation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Fresh RBC Transfusion/Storage-aged RBC Transfusion | Storage-aged RBC Transfusion/Fresh RBC Transfusion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 4 Participants | 12 Participants |
| Region of Enrollment United States | 9 participants | 6 participants | 15 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 |
| other Total, other adverse events | 0 / 9 | 0 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 |
Outcome results
Primary
Change in Flow-mediated Vasodilation (FMD)
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.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: The data are not stratified by data points/study periods, as the data points were not collected due to non-compliant nature of the enrolled subjects. Majority of the subjects did not complete the study entirety.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fresh RBC Transfusion/Storage-aged RBC Transfusion | Change in Flow-mediated Vasodilation (FMD) | 1.83333 percentage of FMD | Standard Deviation 3.900427 |
| Storage-aged RBC Transfusion/Fresh RBC Transfusion | Change in Flow-mediated Vasodilation (FMD) | -3.56667 percentage of FMD | Standard Deviation 6.612614 |
Primary
Change in Reactive Hyperemic Index (RHI)
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.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Change in High-sensitivity C-reactive Protein (hsCRP)hsCRP
Levels of high-sensitivity C-reactive protein (hsCRP) in the blood will be measured by using Dade Behring nephelometry. Higher levels of hsCRP indicate increased vascular inflammation.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Change in Levels of IL-2
Plasma IL-2 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-2 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-2 indicate increased vascular inflammation.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Change in Levels of IL-6
Plasma IL-6 concentration will be measured by enzyme-linked immunosorbent assay (ELISA). Change is the difference in the levels of IL-6 from baseline to Day 1 (first post-transfusion day). Higher concentrations of IL-6 indicate increased vascular inflammation.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Change in Levels of Nitric Oxide Metabolites
Nitric oxide metabolites like nitrite, nitrate, S-nitrosothiols (SNO-Hb and SNO-thiol) will be measured from blood samples using high-performance liquid chromatography (HPLC). Higher levels of nitric oxide metabolites indicate higher levels of nitric oxide (NO) synthesis and better vascular reactivity.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Change in Oxidative Stress Markers
Oxidative stress will be measured using high-performance liquid chromatography (HPLC) to collect plasma cystine, cysteine, glutathione, and glutathione disulfide levels. Higher levels of cystine, cysteine, glutathione, and glutathione disulfide indicate higher levels of vascular inflammation.
Time frame: Baseline (prior to transfusion), Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Maximal Oxygen Uptake (VO2Max)
Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Maximal oxygen uptake (VO2Max) is the value achieved when the oxygen uptake remains stable despite a progressive increase in the intensity of exercise. The VO2Max will be calculated from the cardiac output and the arteriovenous oxygen difference during peak exercise. VO2Max is expressed in milliliters of oxygen per minute per kilogram of body weight (ml/min/kg). A higher VO2Max indicates better vascular reactivity.
Time frame: Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
O2 Pulse
Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. O2 (oxygen) pulse is the amount of O2 consumed from the volume of blood delivered to tissues by each heartbeat; this index is calculated as: O2 pulse = VO2 / heart rate. A higher O2 pulse indicates better vascular reactivity.
Time frame: Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Peak VO2 Lean
Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. Peak VO2 lean is the peak oxygen uptake adjusted for lean body mass and is reported as a lean body weight-adjustment parameter in mL/kg per minute.
Time frame: Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.
Secondary
Respiratory Exchange Ratio (RER):
Subjects will undergo graded treadmill testing following American Heart Association guidelines using the modified Balke protocol. A treadmill with full metabolic cart will be used for the cardiopulmonary testing. RER is the ratio of VCO2 (carbon dioxide output) to VO2 (oxygen uptake). A higher RER indicates better vascular reactivity.
Time frame: Day 1 (first post-transfusion day)
Population: Data were not collected. The study subjects could not complete the proposed study procedure due to preexisting comorbidities.