Posttransfusion 24‐hour recovery and subsequent survival of allogeneic red blood cells in the bloodstream of newborn infants

Strauss, Ronald G.; Mock, Donald M.; Widness, John A.; Johnson, Karen; Cress, Gretchen A.; Schmidt, Robert L.

doi:10.1111/j.1537-2995.2004.03393.x

Cited by 37 publications

(40 citation statements)

References 21 publications

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“…The life span of transfused RBCs (70.8 days) was taken as the average of two different techniques, namely, biotin labeling (mean estimated life span ϭ 85.2 days) (6) and the decline in fetal Hb percentage (mean estimated life span ϭ 56.4 days) (47). The life span of endogenously produced RBCs was also fixed to 42.5 days on the basis of previous mean estimates using 51 Cr RBC labeling (8).…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…The life spans of the adult transfused (L trans ) was fixed to 70.8 days, the midpoint of the estimated life spans of 56.4 and 85.2 days of transfused adult RBCs in preterm infants (Bard and Widness, 1997;Strauss et al, 2004). In addition, the time between production of progenitor cells outside the circulation to release of the subsequently produced RBCs into the circulation (a) was set equal to 3 days based on previous estimates (Izak, 1977;McKenzie, 1988;Hoffman et al, 2005;Krzyzanski et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, the effects of the physical removal and administration of RBCs are substantial and cannot be ignored. Other complications in determining the erythropoiesis rate in preterm VLBW infants include increases in total blood volume as it expands with infant growth and the mixture of endogenously produced RBCs and exogenously administered adult donor RBCs after transfusion, the former of which generally has shorter life spans (Brugnara and Platt, 2003;Strauss et al, 2004).…”

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confidence: 99%

Erythropoietic Response to Endogenous Erythropoietin in Premature Very Low Birth Weight Infants

Freise

Widness²,

Veng‐Pedersen³

2009

J Pharmacol Exp Ther

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Despite the common occurrence of anemia in very low birth weight (VLBW) infants, the erythropoiesis and Hb production rates and their relationship to plasma erythropoietin (EPO) concentrations remain unknown in these subjects. To determine these quantities, all blood removed by phlebotomy and administered by red blood cell (RBC) transfusion over the first 30 days of life was recorded in 14 ventilated VLBW infants born at 24 to 28 weeks of gestation. Discarded blood from frequent clinically ordered laboratory blood samples was used to construct plasma EPO, Hb, and RBC concentration-time profiles for each infant. A pharmacodynamic Hb mass balance model that accounted for the dynamic hematological conditions experienced by these infants was simultaneously fitted to the plasma EPO, Hb, and RBC concentrations from each individual subject, while accounting for subject growth. Based on the model estimates, an average of 4.69 g of Hb was produced over the first 30 days of life, compared with 5.97 g removed by phlebotomies and 12.3 g administered by transfusions. These high transfusion amounts were consistent with a relatively short RBC life span and rapidly expanding blood volume with infant growth. The estimated mean body weight-scaled Hb production rate dropped nearly 3-fold after birth to 0.144 g/day⅐(kg) 3/4 . Although only estimated in a subset of the subjects, the mean plasma EPO EC 50 of 28.5 mU/ml and maximal Hb production rate (E max ) indicated that a severalfold increase in Hb production rate could be achieved with only a modest increase in plasma EPO concentrations.

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“…RBC survival determinations are rarely performed for clinical purposes, but there are a number of investigational circumstances in which they are useful, including: i) evaluation of RBC storage and pathogen inactivation [33][34][35]; ii) studies of the pathophysiology of sickle cell disease [19][20][21][22]; iii) the importance of RBC lifespan in diabetes as an explanation of mismatches between blood glucose and HbA1c [1]; iv) studies of the optimum RBC transfusion product for premature newborns [17]; v) poorly understood anemias including those associated with chronic inflammation [36] and the elderly; vi) investigations of RBC aging and senescence. Studies of transfusion products require a population-type, ex vivo label.…”

Section: Applicationsmentioning

confidence: 99%

Measurement of Red Cell Lifespan and Aging

Franco

2012

Transfus Med Hemother

183

128

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The measurement of red blood cell (RBC) survival has a long history, and a wide variety of methods have been utilized for this purpose. Current methods are of 2 types. First, those that label a representative sample of RBCs of all ages from the blood and then measure their rate of disappearance upon reinfusion. This category includes the ⁵¹Cr and biotin labels. Second, those that use a metabolic precursor or product to determine the turnover of hemoglobin. Examples of these are carbon monoxide production and incorporation of labeled glycine. Recent studies with the covalent, nonradioactive biotin label show its unique suitability for both the accurate measurement of red cell survival and the determination of changes in red cell properties as they age in vivo.

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Posttransfusion 24‐hour recovery and subsequent survival of allogeneic red blood cells in the bloodstream of newborn infants

Cited by 37 publications

References 21 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

Erythropoietic Response to Endogenous Erythropoietin in Premature Very Low Birth Weight Infants

Measurement of Red Cell Lifespan and Aging

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