Orringer E P, Blythe D S, Johnson A E, Phillips G, Dover G J, Parker J C
Department of Medicine, University of North Carolina at Chapel Hill 27599-7600.
Blood. 1991 Jul 1;78(1):212-6.
A rationale for clinical trials of hydroxyurea (HU) treatment in sickle cell disease is that the agent increases red blood cell (RBC) fetal hemoglobin content. However, an additional effect of HU is to raise the mean corpuscular volume (MCV). To investigate the action of HU in a species that makes no electrophoretically distinguishable fetal hemoglobin, we treated dogs with the drug and compared their response to that of five patients with sickle cell anemia. Both dogs and patients had an increase in MCV, but the effect of HU treatment on the mean corpuscular hemoglobin concentration (MCHC), density, and water content of the RBCs differed in the two species. The dog RBCs became low in MCHC, high in ion and water content, and low in mean density. Thus, HU can raise MCV and lower MCHC without influencing fetal hemoglobin synthesis. A different pattern was seen in the sickle cell patients during HU treatment. Although the MCV of their RBCs increased, there was no change in MCHC, ion content, or mean density. A notable change in the sickle cell patients' blood was that two subpopulations of cells were nearly eliminated during HU treatment; the hypodense reticulocyte fraction and the hyperdense fraction that contains irreversibly sickled cells. These findings lead us to suggest that trials of HU in sickle cell disease must recognize the possibility that any beneficial effect of this agent might be due not only to an increase in hemoglobin F alone, but perhaps also to the associated increase in MCV or the altered RBC density profile.
羟基脲（HU）用于镰状细胞病临床试验的一个理论依据是，该药物可增加红细胞（RBC）中胎儿血红蛋白的含量。然而，HU的另一个作用是提高平均红细胞体积（MCV）。为了研究HU在一种无法通过电泳区分胎儿血红蛋白的物种中的作用，我们用该药物治疗了犬类，并将它们的反应与五名镰状细胞贫血患者的反应进行了比较。犬类和患者的MCV均有所增加，但HU治疗对红细胞平均血红蛋白浓度（MCHC）、密度和含水量的影响在这两个物种中有所不同。犬类红细胞的MCHC降低，离子和含水量升高，平均密度降低。因此，HU可以提高MCV并降低MCHC，而不影响胎儿血红蛋白的合成。在HU治疗期间，镰状细胞病患者出现了不同的模式。虽然他们红细胞的MCV增加了，但MCHC、离子含量或平均密度没有变化。镰状细胞病患者血液中的一个显著变化是，在HU治疗期间，两个细胞亚群几乎消失；低密度网织红细胞部分和包含不可逆镰状细胞的高密度部分。这些发现使我们认为，在镰状细胞病中进行HU试验必须认识到，该药物的任何有益作用可能不仅归因于单独的血红蛋白F增加，还可能归因于MCV的相关增加或红细胞密度分布的改变。
