MIXTURES OF RED BLOOD CELL VOLUME DISTRIBUTIONS

这项研究旨在开发一种新的、对诊断有用的 研究人群红细胞体积分布的统计方法 贫血。在过去的二十年里，贫血的诊断一直是 通过对红细胞平均体积的可靠估计来促进 电子粒子计数器。目前的全自动血细胞分析仪 测量电子粒子计数器产生的红细胞体积。 目前的自动血液学分析仪测量每个红细胞的体积， 提供红细胞体积分布。由联合国开发的程序 首席调查员(McLaren等人，1986a，1986b，1987) 对单个细胞群体的分析现在已被专家采用 年国际标准化委员会细胞计量小组 血液学(ICSH)作为ICSH参考方法纳入其 关于细胞大小分布分析标准化的建议 (ICSH，1988)这项研究的主要目标是扩展这些程序 以允许检测和表征组成亚群 包含在红细胞体积分布中。不同的原因 贫血可能导致红细胞体积的特征性改变。 分发。识别红细胞体积形式的变化 分布可能具有诊断价值，因为贫血的某些原因 保持形状不变(例如，许多低增殖状态) 其他疾病形式有时会因存在而改变 红血球亚群。尽管细胞群体的混合可以 发生在某些血液疾病(早期离子缺乏或其他类型的 营养性贫血、骨髓增生异常综合征和铁粒母细胞贫血) 将整个分布划分为亚群的工作受到了阻碍 由于缺乏刻画双截断的统计方法 分配。提供有效的统计方法用于分析 多个细胞群体的分布，这项研究项目 HAS针对特定目标：(1)设计用于分配的迭代算法 适用于RED的参数估计和拟合优度检验 血细胞体积数据；(2)确定下列统计条件 可以检测到哪些双截断对数正态分布的混合 通过对计算机模拟混合物的分析；(3)验证了模型的准确性 用体外混合血液分析混合分布的方法 具有不同平均细胞体积和体内混合血液的样本 治疗后的缺铁性贫血患者的样本，维生素B12 缺乏和叶酸缺乏；和(4)应用这些统计 中国疾病患者血液样本的研究程序 可能存在哪些红细胞亚群，例如骨髓增生异常 贫血和铁粒母细胞性贫血。这些新的统计技术适用于 包含多个群体的红细胞体积分布分析 有助于使新的诊断信息普遍可用 从目前的电子颗粒计数器衍生而来，为临床提供了一种 改进贫血评估和管理的有效方法。

This research is designed to develop a new, diagnostically useful statistical method for the study of red cell volume distributions in anemia. Over the past two decades the diagnosis of anemia has been facilitated by reliable estimates of the mean volume of red cells made by electronic particle counters. current automated hematology-analyzers measure the volume of red cells made by electronic particle counters. Current automated hematology-analyzers measure the volume of each red cell, providing the red cell volume distribution. Procedures developed by the Principal Investigator (McLaren el al., 1986a, 1986b, 1987) for the analysis of single populations of cells have now been adopted by the Expert Panel on Cytometry of the International Committee for Standardization in Hematology (ICSH) for inclusion as an ICSH Reference Method in their recommendations for the standardization of cell size distribution analysis (ICSH, 1988) The major goal of this research is to extend these procedures to permit the detection and characterization of component subpopulations contained within red blood cell volume distributions. Different causes of anemia may result in characteristic alterations in the red cell volume distribution. Recognizing changes in the form of the red cell volume distribution may be diagnostically valuable because some causes of anemia leave the shape unaltered (e.g., many hypoproliferative states), while in other disorders the form is changed sometimes by the presence of subpopulations of red cells. Although mixtures of populations of cells may occur in some blood disorders (early ion deficiency or other types of nutritional anemias, myelodysplastic syndromes, and sideroblastic anemia) separation of the entire distribution into subpopulations has been hampered by lack of statistical methods for characterization of doubly-truncated distributions. To provide valid statistical methods for analysis of distributions with multiple populations of cells, this research project has for specific aims: (1) devise iterative algorithms for distribution parameter estimation and goodness of fit testing suitable for use with red blood cell volume data; (2) determine the statistical conditions under which mixtures of doubly-truncated lognormal distributions can be detected by analysis of computer simulated mixtures; (3) verify the accuracy of the method for analysis of mixed distributions using in vitro mixtures of blood samples with different mean cell volumes and in vivo mixtures of blood samples from patients with treated iron deficiency anemia, vitamin B12 deficiency, and folate deficiency; and (4) apply these statistical procedures in studies of blood samples from patients with disorders in which subpopulations of red cells may be present, e.g. myelodysplastic anemia and sideroblastic anemia. These new statistical techniques for the analysis of red cell volume distributions containing multiple populations of cells will help make generally available the new diagnostic information derived from current electronic particle counters and provide a clinically useful approach to improving the evaluation and management of anemia.