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.

中文翻译：

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放血所致贫血新生小鼠的血液学变化

背景

贫血是早产儿的一种几乎普遍的诊断，由放血引起，并因潜在的红细胞生成不成熟而加剧。新生儿面临着从胎儿到新生儿过渡的独特压力源，这需要在子宫外进行显着的适应。因此，早产儿对贫血的反应可能会改变其应对潜在疾病的能力。本研究利用我们的放血诱发贫血 (PIA) 临床前小鼠模型来全面研究相关的血液学变化。

方法

C57BL/6 小鼠在出生后 2--10 天之间进行定时放血以诱导严重贫血。全血细胞计数由 Sysmex XT-2000iV 分析仪测定。

结果

贫血幼仔表现出红细胞和血红蛋白 (Hb) 逐渐减少，网织红细胞 (RET) 计数和红细胞分布宽度 (RDW) 增加，但从出生后第 4 天 (P) 开始，RET-Hb 减少。贫血小鼠幼仔中高荧光 RET 和未成熟网织红细胞分数 (IRF) 水平升高，但低和中荧光 RET 水平降低。此外，贫血幼犬的平均红细胞体积（MCV）、平均红细胞血红蛋白（MCH）和平均红细胞血红蛋白浓度（MCHC）也有所减少。淋巴细胞未见变化，但单核细胞和中性粒细胞较 P4-P6 显着升高。

结论

幼鼠的 PIA 与血液学变化有关，而血液学变化可能是加剧新生儿疾病的因素。

影响

• 贫血在早产儿中很常见，而且往往很严重。

• 临床前贫血情况下血液学参数的研究可能是治疗策略的一个指标。

• 临床前模型评估新生儿贫血对全血细胞计数剩余部分的影响。

• 详细的时间动力学放血诱导的贫血小鼠使我们能够研究对红细胞生成发育迟缓的影响以及可能的策略干预。

• 小鼠严重贫血的血液学影响可能为如何最好地研究早产儿贫血提供见解。