Abstract
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
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Anemia is common and often severe in premature infants.
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Investigation of hematological parameters in settings of preclinical anemia may be an index of therapeutic strategies.
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Preclinical model evaluating the effects of neonatal anemia on the remainder of complete blood count.
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Detailed time kinetic phlebotomy-induced anemic mice enable us to study the impact on developmental delays in erythropoiesis and possible strategic intervention.
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Hematological effects of severe anemia in mice might provide insight on how best to investigate anemia in preterm infants.
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Acknowledgements
The authors acknowledge Sysmex America, Scientific Marketing Department for the instrument loan (Sysmex XT-2000iV) and technical support.
Funding
This study was supported by the National Institutes of Health awards HL124078, HL133022, and HD105880 (to K.M.)
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K.M. designed the study and wrote the manuscript; Y.C., S.D., K.N., P.G., L.H., and K.M. performed key experiments and data analysis. All the authors contributed to and approved the manuscript.
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Chung, Y., Desiraju, S., Namachivayam, K. et al. Hematological changes in neonatal mice with phlebotomy-induced anemia. Pediatr Res 92, 1575–1579 (2022). https://doi.org/10.1038/s41390-022-02023-w
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DOI: https://doi.org/10.1038/s41390-022-02023-w
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