Schwartz A B, Orquiza C S
Department of Medicine, Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102-1197, USA.
Clin Nephrol. 1995 Apr;43(4):256-9.
In historical studies erythropoietin stimulated bone marrow was shown to produce less stable, macrocytic, "stress erythrocytes". Recent work from our lab suggests that erythropoietin serves as both a growth factor and as a survival factor. To investigate the effects of recombinant human erythropoietin (rHuEPO) on development of red blood cell size of these longer lived erythrocytes, rHuEPO in 50-150 U/kg/dose was administered to patients with the anemia of chronic renal failure (CRF). Mean corpuscular volume (MCV) was determined at control, short term (n = 117, avg. 53 d), intermediate term (n = 73, avg. 136 d) and at long term (n = 66, avg. 221d) for effects of rHuEPO. Statistical evaluation at these time points was made comparing all patients to themselves as their own controls and using contingency tables for distribution of RBC size change. MCV at both short term (p = .02) and intermediate-term (p < .01) was decreased; there was no change (p = .71) at the long term. Analysis of distribution showed a significant (p < .01) trend toward microcytosis at short- and intermediate terms. This decrease of MCV and trend toward microcytosis is consistent with iron deficiency secondary to the early, rapid increase in bone marrow iron utilization and early increased reticulocytosis. Previous reports from our laboratory coupled with data presented in this report refute earlier findings that rHuEPO creates a "stress" mechanism producing less stable macrocytes.
在历史研究中,促红细胞生成素刺激的骨髓被证明会产生稳定性较差的大红细胞,即“应激红细胞”。我们实验室最近的研究表明,促红细胞生成素既是一种生长因子,也是一种存活因子。为了研究重组人促红细胞生成素(rHuEPO)对这些寿命较长的红细胞大小发育的影响,对慢性肾衰竭(CRF)贫血患者给予50 - 150 U/kg/剂量的rHuEPO。在对照期、短期(n = 117,平均53天)、中期(n = 73,平均136天)和长期(n = 66,平均221天)测定平均红细胞体积(MCV),以观察rHuEPO的作用。在这些时间点进行统计评估时,将所有患者自身作为对照,并使用列联表分析红细胞大小变化的分布情况。短期(p = 0.02)和中期(p < 0.01)时MCV均降低;长期时无变化(p = 0.71)。分布分析显示,短期和中期有显著(p < 0.01)的小红细胞增多趋势。MCV的降低和小红细胞增多趋势与骨髓铁利用早期快速增加及早期网织红细胞增多继发的缺铁一致。我们实验室之前的报告以及本报告中的数据反驳了早期的研究结果,即rHuEPO会产生一种导致生成稳定性较差的大红细胞的“应激”机制。