A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy
A multiparameter analysis of sickle erythrocytes in patients undergoing hydroxyurea therapy
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DOI：
10.1182/blood.v88.12.4701.bloodjournal88124701
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发表时间：
1996-12-15
期刊：
影响因子：
20.3
通讯作者：
Eaton, WA
中科院分区：
文献类型：
--
作者：
Bridges, KR;Barabino, GD;Eaton, WA
在24周的羟基尿素治疗期间，我们监测了3例镰状细胞病患者的红细胞参数，包括F细胞和F网织红细胞的分布，细胞内聚合延迟时间的分布，层流室中镰刀状红细胞与人脐静脉内皮细胞的黏附，RBC邻苯二甲酸盐密度分布，平均红细胞血红蛋白浓度和阳离子含量，网织红细胞平均红细胞血红蛋白浓度，H-1核磁共振压缩红细胞横向驰豫速率，以及带3和糖角蛋白的质膜侧向和旋转迁移率。羟基脲增加了在聚合开始前具有足够长的延迟时间以逃离微循环的细胞的比例。此外，仅在羟基脲治疗2周后，镰刀状红细胞对人脐静脉内皮细胞的高粘附性降低到正常水平，先于胎儿血红蛋白水平的增加。镰刀状红细胞与内皮细胞的低粘附性有助于在聚合开始前逃离微循环。羟基尿素使镰状红细胞的几个生化和生物物理参数向观察到的血红蛋白SC病的值移动，这表明羟基尿素缓和了镰状细胞病向较轻但仍具有临床意义的血红蛋白SC病的方向。在镰刀细胞疾病中羟基尿素的多中心研究中记录的镰刀危机减少了50%，这与红细胞改善的程度是一致的。这是美国政府的工作。它的使用没有任何限制。
During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human umbilical vein endothelial cells in a laminar flow chamber, RBC phthalate density profiles, mean corpuscular hemoglobin concentration and cation content, reticulocyte mean corpuscular hemoglobin concentration, H-1-nuclear magnetic resonance transverse relaxation rates of packed RBCs, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with sufficiently long delay times to escape the microcirculation before polymerization begins. Furthermore, high pretreatment adherence to human umbilical vein endothelial cells of sickle RBCs decreased to normal after only 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium would facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parameters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease toward the milder, but still clinically significant, hemoglobin SC disease. The 50% reduction in sickle crises documented in the Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with this degree of erythrocyte improvement. This is a US government work. There are no restrictions on its use.