Clinical Trial: Red Blood Cell (RBC) Survival Following Transfusion in Infants

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Red Blood Cell Survival Following Transfusion in Infants

Brief 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.

Detailed Summary:

Phase I: Includes only Aim #1 from Thrasher Foundation Grant in which adult subjects will be studied.

SPECIFIC AIM #1 (Thrasher Foundation Grant): To develop in vitro and validate in vivo in adult humans and anemic infants the capability of biotinylating RBCs at up to 5 discrete densities for simultaneously determining RBC kinetics of multiple, distinct RBC populations. This requires expansion of the RBC biotin labeling technology we have previously developed. After refinement, the method will be applied in the subsequent aims conducted in anemic infants receiving clinically ordered RBC transfusions.

As suggested by our previous RBC survival studies, we anticipate that the heaviest biotin labeling will alter the intrinsic RBC structural properties of RBCs, shortening their long term survival. The in vitro and in vivo validation studies we propose in adults are necessary because the conditions for reproducibly obtaining discrete RBC biotin densities at appropriate, closely spaced intervals have not been conclusively worked out, nor have we determined empirically which of the five densities will not artifactually shorten long-term RBC survival. We can use the lighter densities for RBC survival measurements and the heavier densities for the simultaneous RBC volume measurements needed to account for RBC volume increases caused by growth. It is important to perform these feasibility studies in both adults and infants because of the vastly different physiologic states, ie, normal, healthy adults are in steady state erythropoiesis while critically ill, anemic infants experience multiple clinical circumstances which perturb RBC survival, eg, growth, phlebotomy, intervening transfusion, etc.

In addition to the biotin labeling of RBC method, the "differential agglutination, anti
Sponsor: University of Iowa

Current Primary Outcome:

  • Measurement of biotinylated RBCs at up to 5 discrete densities by flow cytometry. [ Time Frame: from date of transfusion to disappearance of biotinylated RBCs in blood samples, typically 4 months. ]
  • RBC survival in days of multiple, distinct populations of transfused RBCs in premature infants. [ Time Frame: 20 minutes - 4 months ]
  • Long-term survival of transfused adult donor and fetal/placental RBCs in days in anemic newborn infants. [ Time Frame: 20 min - 6 months ]


Original Primary Outcome: To develop in vitro and validate in vivo in adults the capability for biotinylating RBCs at up to 5 discrete densities that are measurable by flow cytometry. [ Time Frame: 5 min - 6 mo post transfusion of biotin RBC's ]

Current Secondary Outcome:

  • Positive antibody screen in response to biotin-labeled RBCs. [ Time Frame: 5 min - 6 mo post transfusion of biotin RBCs ]
  • Survival of RBCs in days as measured by the differential agglutination, antigenic method [ Time Frame: 5 min to 5 months ]


Original Secondary Outcome: To assess if antibodies to biotin-labeled RBCs may develop and to assess if the biotinylated RBCs may be removed ot destroyed by the subject's circulatory system. [ Time Frame: 5 min - 6 mo post transfusion of biotin RBCs ]

Information By: University of Iowa

Dates:
Date Received: August 5, 2008
Date Started: June 2008
Date Completion:
Last Updated: December 23, 2014
Last Verified: December 2014