Cazzola M, Guarnone R, Cerani P, Centenara E, Rovati A, Beguin Y
Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Liege, Liege, Belgium.
Blood. 1998 Mar 15;91(6):2139-45.
Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.
血清促红细胞生成素（sEpo）浓度主要与肾脏生成速率相关，并且在缺氧刺激下，随着血红蛋白（Hb）降低呈指数增加。然而，其他因素似乎也会影响sEpo，在本研究中，我们开展了多项研究以评估红细胞前体数量的作用。我们首先比较了红细胞生成活性低和高的患者中sEpo与Hb的关系。第一组包括27例红细胞再生障碍或发育不全患者，其血清转铁蛋白受体（sTfR）水平<3mg/L（红细胞生成活性<正常的0.6倍），而第二组包括28例中间型β地中海贫血患者，其sTfR水平>10mg/L（红细胞生成活性>正常的2倍）。两组患者的Hb水平无差异（8.3±1.6 vs 8.0±1.3g/dL，P>.05），但红细胞生成活性低的患者sEpo水平显著更高（1,601±1,542 vs 235±143mU/mL，P<.001）。实际上，多变量方差分析（ANOVA）显示，在任何给定的Hb水平下，红细胞生成活性低的患者sEpo更高（P<.0001）。随后对20例接受同种异体或自体骨髓移植（BMT）的患者进行了研究。在所有患者骨髓再生障碍时均观察到sEpo显著增加，与Hb水平的小幅下降相比，增加幅度不成比例地高。还对5例接受静脉（IV）铁剂治疗的缺铁性贫血患者进行了系列研究。在开始铁剂治疗后的24至72小时内，在Hb水平出现任何变化之前，发现sEpo显著下降（高达一个对数单位）。在巨幼细胞贫血患者和一例纯红细胞再生障碍患者中也观察到了类似现象。这些发现表明红细胞前体数量与sEpo之间存在负相关：在任何给定的Hb水平下，红细胞前体数量越多，sEpo浓度越低。对此最可能的解释是，sEpo水平不仅受肾脏生成速率的调节，还受红细胞系细胞利用速率的调节。
