Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities

Mock, Donald M.; Matthews, Nell I.; Zhu, Shan; Strauss, Ronald G.; Schmidt, Robert L.; Nalbant, Demet; Cress, Gretchen A.; Widness, John A.

doi:10.1111/j.1537-2995.2010.02926.x

Cited by 83 publications

(180 citation statements)

References 28 publications

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“…In the present analysis, transfused RBCs were assumed to have a constant rate of senescence. This assumption is supported by previous studies reporting a linear decline in RBC survival in adult humans (30,35). Another possible factor that was not considered in the present analysis is storage time.…”

Section: R776 Population Pd Modeling Of Erythropoiesis In Preterm Infsupporting

confidence: 74%

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Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin

Saleh

Nalbant

Widness

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Saleh MI, Nalbant D, Widness JA, Veng-Pedersen P. Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin. Am J Physiol Regul Integr Comp Physiol 304: R772-R781, 2013. First published March 13, 2013 doi:10.1152/ajpregu.00173.2012.-A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24 -29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity. erythropoiesis; preterm infants; pharmacodynamics; gestational age ANEMIA IS A FREQUENT COMPLICATION in very low birth weight (VLBW) premature infants (birth weight Ͻ1,500 g) that is usually referred to as anemia of prematurity (14). There are two main causes of anemia of prematurity: insufficient erythropoietin (EPO) production and heavy blood loss resulting from frequent laboratory blood sampling (53). Previous studies have shown that during the first 4 wk of life in preterm infants with a gestational age Ͻ28 wk or birth weights Ͻ1 kg, approximately twice the volume of red blood cells (RBCs) transfused relative to the volume removed for laboratory blood testing (50). Thus the effect of blood sampling is substantial and must be considered in the management of anemia and in the assessment of erythropoiesis in preterm infants. Anemia of prematurity is also exacerbated by other factors such as shortened RBC life span and the rapid expansion of blood volume with growth (32).For many years, RBC transfusion was the only effective treatment for severe anemia of prematurity. In 1987, the first clinical trial of EPO demonstrated that EPO treatment was demonstrated to reduce the need for RBC transfusions in adults with end-stage renal disease (18). Subsequently, there has been a series of reports demonstrating variable results regarding th...

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Section: R776 Population Pd Modeling Of Erythropoiesis In Preterm Infsupporting

confidence: 74%

“…(i.e., exhibited constant breakdown rate) (30,35). The change in the amount of transfused Hb for the ith transfusion, resulting from an amount of Hb T i transfused at time t tran i was described by a zero-order process as displayed in Eq.…”

Section: R773 Population Pd Modeling Of Erythropoiesis In Preterm Infmentioning

confidence: 99%

Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin

Saleh

Nalbant

Widness

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…After a 30-min reaction, the BioRBCs were washed twice, filtered, and transfused. The percent of BioRBCs in posttransfusion blood samples was determined by flow cytometric enumeration after staining with avidin conjugated with Alexa Fluor 488 as previously described (21,22). Cord blood/infant autologous RBCs were biotinylated as described earlier and reinfused back into the same infant.…”

Section: Biotinylation Of Rbcs and Facs Analysismentioning

confidence: 99%

“…The measurement of red cell survival using RBCs labeled with biotin (BioRBCs) is practical, reliable, accurate, and safe (21)(22)(23). RBCs were labeled with biotin as previously described (21,22).…”

Section: Biotinylation Of Rbcs and Facs Analysismentioning

confidence: 99%

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A Method to Evaluate Fetal Erythropoiesis from Postnatal Survival of Fetal RBCs

Kuruvilla

Widness

Nalbant

et al. 2015

AAPS J

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Abstract. Fetal RBCs are produced during a period of very rapid growth and stimulated erythropoiesis under hypoxic intrauterine conditions. Fetal RBC life span varies with gestational age (GA) and is shorter than that in healthy adults. Due to the special kinetic properties of life span-based survival of human RBCs, a mathematical model-based kinetic analysis of the survival of fetal RBCs shortly after birth provides a unique opportunity to Blook backward in time^to evaluate fetal erythropoiesis. This work introduces a novel method that utilizes postnatal in vivo RBC survival data collected within 2 days after birth to study both nonsteady-state (non-SS) in utero RBC production and changing fetal RBC life span over time. The effect of changes in erythropoiesis rate and RBC life span and the effect of multiple postnatal phlebotomies on the RBC survival curves were investigated using model-based simulations. This mathematical model, which considers both changes in the rate of erythropoiesis and RBC life span and which accurately accounts for the confounding effect of multiple phlebotomies, was applied to survival curves for biotin-labeled RBCs from ten anemic very low birth weight preterm infants. The estimated mean fetal RBC production rate scaled by body weight was 1.07×107 RBCs/day g, and the mean RBC life span at birth was 52.1 days; these values are consistent with reported values. The in utero RBC life span increased at a rate of 0.51 days per day of gestation. We conclude that the proposed mathematical model and its implementation provide a flexible framework to study in utero non-SS fetal erythropoiesis in newborn infants.

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The Transfusion of Red Cells

2013

Mollison's Blood Transfusion in Clinical Medicine

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Red blood cell (RBC) survival determined in humans using RBCs labeled at multiple biotin densities

Cited by 83 publications

References 28 publications

Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin

Population pharmacodynamic analysis of erythropoiesis in preterm infants for determining the anemia treatment potential of erythropoietin

A Method to Evaluate Fetal Erythropoiesis from Postnatal Survival of Fetal RBCs

The Transfusion of Red Cells

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