Red Blood Cell (RBC) Survival Following Transfusion in Infants
Condition: Neonatal Anemia
MeSH terms: Anemia, Neonatal
Intervention: Transfused Biotin RBCs - Adults Phase I; Transfused Biotin RBCs - Infants Phase II; Transfused Biotin RBCs - Infants Phase III
Intervention description: A 3 mL venous blood sample is obtained. 250 mL of blood will be drawn to a blood collection bag containing the anticoagulant CPD. Separate equal volumes of RBCs are labeled with up to five different densities of biotin. The biotinylated RBCs are resuspended in autologous plasma to achieve a 60 to 70% hematocrit. An IV is inserted for the reinfusion of the biotinylated RBCs. Three mL aliquots of blood are sampled at 5, 10, 20, and 60 minutes after infusion. The subject returns ~24 hours and 3 days after the RBC infusion to obtain a 3 mL venous blood sample. Subjects return for weekly 3 mL blood sampling.; After the infant's clinical care team decides that a RBC transfusion is needed, a 15mL/kilogram of body weight is ordered. Transfusion will be given in 2 parts: 1) approximately 80% of the total transfusion to be transfused over 3-4 hours and 2) approximately 20% of the total transfusion will be marked with biotin to be transfused upon completion of the first part. The bedside nurse maintains constant observation of the infant as appropriate for the infant's condition, assessing for signs and symptoms of a transfusion reaction.; Phase III (infants) to be determined upon completion of Phase II (infants).
Intervention MeSH terms: Biotin
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 140.0
Sex: All
Minimum age: 1 Hour
Maximum age: 6 Months
Healthy volunteers: No

Summary:

      OUR OVERALL HYPOTHESIS is that post-transfusion survival of allogeneic and autologous RBCs
      can be accurately quantified in anemic human infants using biotin-labeled RBCs combined with
      mathematical modeling that adjusts for confounding factors commonly encountered in neonates.
      These confounding factors include 1) dilution of labeled RBC as a result of growth stimulated
      erythropoiesis, anemia stimulated erythropoiesis, and blood transfusion; 2) loss of labeled
      RBC due to laboratory phlebotomy; and 3) variable RBC life spans resulting from RBCs having
      been produced at different developmental periods and under varying rates of erythropoiesis.
      In contrast to infants, adjustment for these factors is not necessary in healthy adults under
      conditions of steady state erythropoiesis. Instead in adults, RBC survival is typified by a
      linear decline in concentration of labeled RBCs over time. When this line is extrapolated to
      zero concentration, the intercept with the time axis represents the mean potential lifespan
      (MPL) of RBCs. (<7 d) and stored (>21 d) allogeneic adult RBCs transfused in the same infant.
    

Eligibility criteria:

        Adult Study:

        Inclusion Criteria:

          -  Males or post-menopausal females

          -  18-65 years of age.

          -  Weight >110 lbs.

          -  Healthy- the subject feels well and can perform normal activities.

          -  Hemoglobin at or above 12.5 g/dL or hematocrit at or above 38%.

               -  Note: Members of the research team that are not supervised or under the employee
                  of the PI may participate in the study.

        Exclusion Criteria:

          -  Presence of chronic illness unless the subject is being treated and the condition is
             under control.

          -  Consumption of biotin supplements or raw eggs.

          -  Premenopausal women.

          -  Blood donation in the previous 8 weeks (single donation) or 16 weeks (double red cell
             donation).

          -  Blood loss in the previous 8 weeks due to epistaxis, gastrointestinal blood loss,
             trauma, significant diagnostic phlebotomy loss (i.e., > 30 mL total), or other
             significant bleeding

          -  Treatment with antibiotics within the last 7 days. Antibiotics for prevention of an
             infection or treatment of acne are not exclusion criteria.

               -  Note: If study subjects experience any of these conditions associated with blood
                  loss or donate any blood products, they will not be included in the primary
                  analysis but will be replaced.

        Infant Study:

        MOTHERS FOR PLACENTAL BLOOD COLLECTION AND MOTHERS OF INFANT STUDY SUBJECTS

        Inclusion Criteria:

          1. >/= 24 weeks gestation

          2. mothers who deliver through the birth canal or by c-section can be included in the
             study.

        Exclusion Criteria:

          1. Pregnant with fetus with major congenital anomaly.

          2. Clinically suspected or documented maternal chorioamnionitis (This only applies to
             infant study subjects receiving autologous RBCs from the placenta).

          3. Viral or bacterial infection (e.g. HIV, Hepatitis B, Hepatitis C, Primary Herpes,
             Tuberculosis) based on clinically available prenatal or postnatal test results in the
             mother's medical record. (This only applies to infant study subjects receiving
             autologous RBCs from the placenta.)

          4. minor mothers (<18 years old) are excluded from the study.

        INFANT STUDY SUBJECTS

        Inclusion Criteria:

        Newborns >/=24 weeks gestation who are patients in the Neonatal Intensive Care Unit (NICU)
        at UIHC that:

        1) Are being treated with the expectation of survival.

        Exclusion Criteria:

          1. Difference of more than 5% in the percentage of HbF cells (measured by flow cytometry
             in the Widness lab) between blood harvested from the placenta and that from discarded
             neonatal blood in the first day of life and before the first neonatal blood
             transfusion. This is done to exclude the rare possibility of transfusing newborns with
             blood that is contaminated with a significant proportion of their mother's blood if a
             maternal-to-placenta bleed occurs after umbilical cord clamping is done. (This only
             applies to infant study subjects receiving autologous RBCs from the placenta.)

          2. Need of emergent blood transfusion as determined by the subject's medical care team.

          3. Hematological diseases (except for anemia associated with phlebotomy loss and
             prematurity)

          4. Alloimmune hemolytic anemia, diffuse intravascular coagulation, and thrombosis.

          5. Major congenital anomaly.

          6. Sepsis with positive blood or spinal fluid culture.

          7. Receiving treatment with erythropoietin (r-HuEPO) or cardiorespiratory bypass support
             (ECMO).

          8. Overt clinical bleeding.