Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease.
Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease.
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DOI：
10.1002/ajh.23982
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发表时间：
2015-05
影响因子：
12.8
通讯作者：
Higgins JM
中科院分区：
文献类型：
--
作者：
Patel HH;Patel HR;Higgins JM
红细胞（RBC）体积变异（RDW）增加最近已被证明可以预测广泛的死亡率和发病率：心血管疾病，癌症，感染，肾脏疾病等导致的死亡;心力衰竭和冠状动脉疾病的并发症，许多癌症的晚期和预后不良，自身免疫性疾病的预后不良等等。所有这些疾病导致RDW增加的机制尚不清楚。在这里，我们使用一个半机械的数学模型，在体内红细胞群体动力学来剖析控制RDW的因素，并表明，RDW升高的结果主要是从体内红细胞周转率略有下降。随着年龄的增长，红细胞会变得更小，红细胞周转率的轻微降低允许更小的细胞继续循环，扩大红细胞群体体积分布的低体积尾部，从而增加RDW。我们的研究结果表明，轻度延长红细胞寿命是一种以前未被认识到的稳态适应，常见于非常广泛的病理状态，可能补偿红细胞生成量的轻微减少。基于数学模型的清除率估计可能为广泛的发病率和死亡率提供新的早期预警生物标志物。
Increased red blood cell (RBC) volume variation (RDW) has recently been shown to predict a wide range of mortality and morbidity: death due to cardiovascular disease, cancer, infection, renal disease, and more; complications in heart failure and coronary artery disease, advanced stage and worse prognosis in many cancers, poor outcomes in autoimmune disease, and many more. The mechanisms by which all of these diseases lead to increased RDW are unknown. Here we use a semi-mechanistic mathematical model of in vivo RBC population dynamics to dissect the factors controlling RDW and show that elevated RDW results largely from a slight reduction in the in vivo rate of RBC turnover. RBCs become smaller as they age, and a slight reduction in the rate of RBC turnover allows smaller cells to continue circulating, expanding the low-volume tail of the RBC population’s volume distribution, and thereby increasing RDW. Our results show that mildly extended RBC lifespan is a previously unrecognized homeostatic adaptation common to a very wide range of pathologic states, likely compensating for subtle reductions in erythropoietic output. A mathematical model-based estimate of the clearance rate may provide a novel early-warning biomarker for a wide range of morbidity and mortality.