Hematological changes in neonatal mice with phlebotomy-induced anemia.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
06
10
2021
accepted:
06
03
2022
revised:
18
11
2021
pubmed:
25
3
2022
medline:
24
12
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Anemia is a nearly universal diagnosis in preterm infants, caused by phlebotomy, and exacerbated by the underlying erythropoietic immaturity. Newborn infants are exposed to the unique stressor of fetal-to-neonatal transition, which requires significant adaptation ex utero. Accordingly, the preterm infant's response to anemia may alter the ability to confront underlying illness. This study utilized our preclinical mouse model of phlebotomy-induced anemia (PIA) to comprehensively investigate associated hematological changes. C57BL/6 mice were subjected to timed phlebotomy between postnatal days 2--10 to induce severe anemia. Complete blood counts were determined by the Sysmex XT-2000iV analyzer. Anemic pups showed a gradual reduction of RBC and hemoglobin (Hb) and increased reticulocyte (RET) counts and red cell distribution width (RDW), however, with reduced RET-Hb from postnatal day (P) of 4 onwards. Elevated levels of high fluorescent RET and immature reticulocyte fraction (IRF) were noted in anemic mouse pups, but low and medium fluorescent RET were reduced. Also, the reduction of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were noted in anemic pups. No changes were seen in lymphocytes, but monocytes and neutrophils were significantly elevated from P4-P6. PIA in mouse pups is associated with hematological changes that may be exacerbating factors in neonatal diseases. Anemia is common and often severe in premature infants. Investigation of hematological parameters in settings of preclinical anemia may be an index of therapeutic strategies. Preclinical model evaluating the effects of neonatal anemia on the remainder of complete blood count. Detailed time kinetic phlebotomy-induced anemic mice enable us to study the impact on developmental delays in erythropoiesis and possible strategic intervention. Hematological effects of severe anemia in mice might provide insight on how best to investigate anemia in preterm infants.
Sections du résumé
BACKGROUND
Anemia is a nearly universal diagnosis in preterm infants, caused by phlebotomy, and exacerbated by the underlying erythropoietic immaturity. Newborn infants are exposed to the unique stressor of fetal-to-neonatal transition, which requires significant adaptation ex utero. Accordingly, the preterm infant's response to anemia may alter the ability to confront underlying illness. This study utilized our preclinical mouse model of phlebotomy-induced anemia (PIA) to comprehensively investigate associated hematological changes.
METHODS
C57BL/6 mice were subjected to timed phlebotomy between postnatal days 2--10 to induce severe anemia. Complete blood counts were determined by the Sysmex XT-2000iV analyzer.
RESULTS
Anemic pups showed a gradual reduction of RBC and hemoglobin (Hb) and increased reticulocyte (RET) counts and red cell distribution width (RDW), however, with reduced RET-Hb from postnatal day (P) of 4 onwards. Elevated levels of high fluorescent RET and immature reticulocyte fraction (IRF) were noted in anemic mouse pups, but low and medium fluorescent RET were reduced. Also, the reduction of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were noted in anemic pups. No changes were seen in lymphocytes, but monocytes and neutrophils were significantly elevated from P4-P6.
CONCLUSIONS
PIA in mouse pups is associated with hematological changes that may be exacerbating factors in neonatal diseases.
IMPACT
Anemia is common and often severe in premature infants. Investigation of hematological parameters in settings of preclinical anemia may be an index of therapeutic strategies. Preclinical model evaluating the effects of neonatal anemia on the remainder of complete blood count. Detailed time kinetic phlebotomy-induced anemic mice enable us to study the impact on developmental delays in erythropoiesis and possible strategic intervention. Hematological effects of severe anemia in mice might provide insight on how best to investigate anemia in preterm infants.
Identifiants
pubmed: 35322186
doi: 10.1038/s41390-022-02023-w
pii: 10.1038/s41390-022-02023-w
pmc: PMC9500113
mid: NIHMS1793401
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1575-1579Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL133022
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL124078
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL163043
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD105880
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120309
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Cibulskis, C. C., Maheshwari, A., Rao, R. & Mathur, A. M. Anemia of prematurity: how low is too low? J. Perinatol. 41, 1244–1257 (2021).
doi: 10.1038/s41372-021-00992-0
Maheshwari, A., Patel, R. M. & Christensen, R. D. Anemia, red blood cell transfusions, and necrotizing enterocolitis. Semin. Pediatr. Surg. 27, 47–51 (2018).
doi: 10.1053/j.sempedsurg.2017.11.009
MohanKumar, K. et al. Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions. Am. J. Physiol. Gastrointest. Liver Physiol. 318, G705–G716 (2020).
doi: 10.1152/ajpgi.00324.2019
Stockman, J. A. 3rd The anemia of prematurity and the decision when to transfuse. Adv. Pediatr. 30, 191–219 (1983).
doi: 10.1016/S0065-3101(22)00579-5
Stockman, J. A. 3rd Anemia of prematurity. Current concepts in the issue of when to transfuse. Pediatr. Clin. North Am. 33, 111–128 (1986).
doi: 10.1016/S0031-3955(16)34972-0
Whitehead, H. V., Vesoulis, Z. A., Maheshwari, A., Rambhia, A. & Mathur, A. M. Progressive anemia of prematurity is associated with a critical increase in cerebral oxygen extraction. Early Hum. Dev. 140, 104891 (2019).
doi: 10.1016/j.earlhumdev.2019.104891
Whitehead, H. V., Vesoulis, Z. A., Maheshwari, A., Rao, R. & Mathur, A. M. Anemia of prematurity and cerebral near-infrared spectroscopy: should transfusion thresholds in preterm infants be revised? J. Perinatol. 38, 1022–1029 (2018).
doi: 10.1038/s41372-018-0120-0
Widness, J. A. Pathophysiology of anemia during the neonatal period, including anemia of prematurity. Neoreviews 9, e520 (2008).
doi: 10.1542/neo.9-11-e520
Kling, P. J. Iron nutrition, erythrocytes, and erythropoietin in the NICU: erythropoietic and neuroprotective effects. Neoreviews 21, e80–e88 (2020).
doi: 10.1542/neo.21-2-e80
Ohlsson, A. & Aher, S. M. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst. Rev. 11, CD004863 (2017).
Ohlsson, A. & Aher, S. M. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst. Rev. 2, CD004863 (2020).
Moreno-Fernandez, J., Ochoa, J. J., Latunde-Dada, G. O. & Diaz-Castro, J. Iron deficiency and iron homeostasis in low birth weight preterm infants: a systematic review. Nutrients 11, 1090 (2019).
Berglund, S., Westrup, B. & Domellof, M. Iron supplements reduce the risk of iron deficiency anemia in marginally low birth weight infants. Pediatrics 126, e874–e883 (2010).
doi: 10.1542/peds.2009-3624
Stockman, J. A. 3rd et al. Anemia of prematurity: determinants of the erythropoietin response. J. Pediatr. 105, 786–792 (1984).
doi: 10.1016/S0022-3476(84)80308-X
Finne, P. H. & Halvorsen, S. Regulation of erythropoiesis in the fetus and newborn. Arch. Dis. Child. 47, 683–687 (1972).
doi: 10.1136/adc.47.255.683
Counsilman, C. E. et al. Iatrogenic blood loss in extreme preterm infants due to frequent laboratory tests and procedures. J. Matern. Fetal Neonatal Med. 34, 2660–2665 (2021).
doi: 10.1080/14767058.2019.1670800
Jakacka, N., Snarski, E. & Mekuria, S. Prevention of iatrogenic anemia in critical and neonatal care. Adv. Clin. Exp. Med. 25, 191–197 (2016).
doi: 10.17219/acem/32065
Rosebraugh, M. R., Widness, J. A., Nalbant, D. & Veng-Pedersen, P. A mathematical modeling approach to quantify the role of phlebotomy losses and need for transfusions in neonatal anemia. Transfusion 53, 1353–1360 (2013).
doi: 10.1111/j.1537-2995.2012.03908.x
Christensen, R. D., Henry, E., Jopling, J. & Wiedmeier, S. E. The CBC: reference ranges for neonates. Semin. Perinatol. 33, 3–11 (2009).
doi: 10.1053/j.semperi.2008.10.010
Jopling, J., Henry, E., Wiedmeier, S. E. & Christensen, R. D. Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics 123, E333–E337 (2009).
doi: 10.1542/peds.2008-2654
Kates, E. H. & Kates, J. S. Anemia and polycythemia in the newborn. Pediatr. Rev. 28, 33–34 (2007).
doi: 10.1542/pir.28.1.33
Farhi, L. E., Plewes, J. L. & Olszowka, A. J. Lung carbonate dehydratase (carbonic anhydrase), CO
Raymond, S. L. et al. Immunological defects in neonatal sepsis and potential therapeutic approaches. Front. Pediatr. 5, 14 (2017).
doi: 10.3389/fped.2017.00014
Arthur, C. M. et al. Anemia induces gut inflammation and injury in an animal model of preterm infants. Transfusion 59, 1233–1245 (2019).
MohanKumar, K. et al. A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions. Nat. Commun. 10, 3494 (2019).
doi: 10.1038/s41467-019-11199-5
White, J. R. et al. Evaluation of hematologic variables in newborn C57/Bl6 mice up to day 35. Vet. Clin. Pathol. 45, 87–95 (2016).
doi: 10.1111/vcp.12314
Parodi, E., Romano, F. & Ramenghi, U. How we use reticulocyte parameters in workup and management of pediatric hematologic diseases. Front. Pediatr. 8, 588617 (2020).
doi: 10.3389/fped.2020.588617
Juul, S. Erythropoiesis and the approach to anemia in premature infants. J. Matern. Fetal Neonatal Med. 25, 97–99 (2012).
Juul, S. Erythropoietin in anemia of prematurity. J. Matern. Fetal Neonatal Med. 25, 80–84 (2012).
doi: 10.3109/14767058.2012.716987
Al-Ghananim, R. T. et al. Reticulocyte hemoglobin content during the first month of life in critically ill very low birth weight neonates differs from term infants, children, and adults. J. Clin. Lab. Anal. 30, 326–334 (2016).
doi: 10.1002/jcla.21859
Wollmann, M., Gerzson, B. M., Schwert, V., Figuera, R. W. & Ritzel Gde, O. Reticulocyte maturity indices in iron deficiency anemia. Rev. Bras. Hematol. Hemoter. 36, 25–28 (2014).
doi: 10.5581/1516-8484.20140009
Ford, J. Red blood cell morphology. Int. J. Lab. Hematol. 35, 351–357 (2013).
doi: 10.1111/ijlh.12082
Kline, N. E. A practical approach to the child with anemia. J. Pediatr. Health Care 10, 99–105 (1996).
doi: 10.1016/S0891-5245(96)90080-2