Adverse Effects of RBC Transfusions: A Unifying Hypothesis
Condition: Healthy Volunteers
Intervention: Fresh blood; Aged blood
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 21 Years
Maximum age: 80 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Blood Transfusions

Summary:

      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). The investigators are trying to determine the nature of these substances in human
      beings when they are transfused "aged" versus "fresh" red blood cells. It is their 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.

      There is evidence that red blood cells produce NO, which normally causes arteries to relax
      and increase blood supply. The investigators 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 their 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.
    

Eligibility criteria:

        Aim 1:

        Inclusion Criteria:

          -  Healthy male or female volunteers (age 21-60 years)

        Must meet guidelines for blood donors including:

          -  standard blood donor history questionnaire

          -  body weight of at least 110 lbs

          -  hemoglobin concentration of at least 12.5 gm/dL

          -  body temperature of no more than 99.5 oF

          -  pulse of 50-100 bpm

          -  blood pressure < 180/100

          -  test negative for the standard battery of blood donor screening tests (anti-HIV, HIV
             RNA, anti-HCV, HCV RNA, HBsAg, anti-HBc, anti-HTLV-I/II, and WNV RNA)

        Aim 1:

        Exclusion Criteria:

          -  Failure to pass the blood donor history questionnaire

          -  Positive results on the standard battery of blood donor screening tests

          -  Failure to meet criteria for donation

        Aim 2:

        Inclusion Criteria:

          -  Healthy male or female volunteers (age 21-80 years)

        Exclusion Criteria:

          -  Presence of intercurrent illness or other chronic diseases

          -  Renal failure (creatinine>1.4 mg/dl)

          -  Pregnancy

          -  Allergies to aspirin

          -  Bleeding disorders

          -  Uncontrolled hypertension with BP > 180 mmHg systolic and > 120 mmHg diastolic

          -  Acute infection in previous 4 weeks

          -  History of substance abuse

          -  Liver failure (Liver enzymes >2x normal)

          -  Inability to give informed consent

          -  Inability to return to Emory for follow-up