Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA.
Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
AAPS J. 2016 Sep;18(5):1182-1191. doi: 10.1208/s12248-016-9923-0. Epub 2016 May 23.
Direct measurement of red blood cell (RBC) survival in humans has improved from the original accurate but limited differential agglutination technique to the current reliable, safe, and accurate biotin method. Despite this, all of these methods are time consuming and require blood sampling over several months to determine the RBC lifespan. For situations in which RBC survival information must be obtained quickly, these methods are not suitable. With the exception of adults and infants, RBC survival has not been extensively investigated in other age groups. To address this need, we developed a novel, physiology-based mathematical model that quickly estimates RBC lifespan in healthy individuals at any age. The model is based on the assumption that the total number of RBC recirculations during the lifespan of each RBC (denoted by N max) is relatively constant for all age groups. The model was initially validated using the data from our prior infant and adult biotin-labeled red blood cell studies and then extended to the other age groups. The model generated the following estimated RBC lifespans in 2-year-old, 5-year-old, 8-year-old, and 10-year-old children: 62, 74, 82, and 86 days, respectively. We speculate that this model has useful clinical applications. For example, HbA1c testing is not reliable in identifying children with diabetes because HbA1c is directly affected by RBC lifespan. Because our model can estimate RBC lifespan in children at any age, corrections to HbA1c values based on the model-generated RBC lifespan could improve diabetes diagnosis as well as therapy in children.
直接测量人类红细胞 (RBC) 的存活率已经从最初的准确但有限的差异凝集技术发展到当前可靠、安全和准确的生物素方法。尽管如此,所有这些方法都很耗时,需要在几个月的时间内多次采血来确定 RBC 的寿命。对于需要快速获得 RBC 存活信息的情况,这些方法并不适用。除了成年人和婴儿外,其他年龄段的 RBC 存活情况尚未得到广泛研究。为了满足这一需求,我们开发了一种新颖的、基于生理学的数学模型,可以快速估计任何年龄段健康个体的 RBC 寿命。该模型基于这样的假设,即在每个 RBC 的寿命期间,RBC 再循环的总数(用 Nmax 表示)对于所有年龄组来说都是相对恒定的。该模型最初使用我们之前的婴儿和成人生物素标记 RBC 研究的数据进行了验证,然后扩展到其他年龄组。该模型生成了以下估计的 2 岁、5 岁、8 岁和 10 岁儿童的 RBC 寿命:62、74、82 和 86 天,分别。我们推测该模型具有有用的临床应用。例如,HbA1c 测试在识别患有糖尿病的儿童时不可靠,因为 HbA1c 直接受到 RBC 寿命的影响。由于我们的模型可以估计任何年龄儿童的 RBC 寿命,因此基于模型生成的 RBC 寿命对 HbA1c 值进行校正可以改善儿童的糖尿病诊断和治疗。