Red Blood Cell (RBC) Survival Following Transfusion in Infants

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.

Conditions

• Neonatal Anemia

Interventions

BIOLOGICAL

Transfused Biotin RBCs - Adults Phase I

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.

BIOLOGICAL

Transfused Biotin RBCs - Infants Phase II

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.

BIOLOGICAL

Transfused Biotin RBCs - Infants Phase III

Phase III (infants) to be determined upon completion of Phase II (infants).

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Thrasher Research Fund

  collaborator OTHER

• John A Widness

  lead OTHER

Principal Investigators

• John A Widness, MD · University of Iowa

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Hour

Max Age

6 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-06-30

Primary Completion

2017-03-31

Completion

2018-03-02

FDA Drug

Yes

Countries

• United States

Study Locations