Charache S
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Adv Pediatr. 1990;37:1-31.
Increased numbers of F cells and large amounts of Hb F/F cell appear to produce clinical benefit in rare variants of sickle cell disease and probably in more commonly encountered patients. Fetal hemoglobin interferes with polymerization of Hb S in vitro, but laboratory studies carried out with homogeneous hemoglobin solutions are inadequate models of events in vivo, because RBCs are heterogeneous in their MCHC and Hb F content. Studies of hemoglobin switching in sheep, in tissue culture, and then in baboons led to use of 5-azacytidine for induction of increased Hb F synthesis in SS patients. Drug trials were successful but the theory that led to them was not. An alternate theory, not without flaws, led to the use of hydroxyurea. Chronic administration of the drug can lead to very impressive increases in Hb F synthesis and apparent clinical benefit. It is not clear that such clinical benefit is real rather than a placebo effect. Nor is it entirely clear that all of the effect of hydroxyurea can be related to increased production of F cells and increased F/F cell. Controlled clinical trials and studies of the properties of RBCs from treated patients may answer those questions. It is also likely that they will not only raise still other questions but probably show that our current understanding of the biology and treatment of sickle cell disease is far from complete.
在镰状细胞病的罕见变异型中，F细胞数量增加以及大量Hb F/F细胞似乎能产生临床益处，在更常见的患者中可能也是如此。胎儿血红蛋白在体外会干扰Hb S的聚合，但使用均一血红蛋白溶液进行的实验室研究并非体内情况的充分模型，因为红细胞在平均血红蛋白浓度（MCHC）和Hb F含量方面存在异质性。对绵羊、组织培养以及随后对狒狒的血红蛋白转换研究，促使人们使用5-氮杂胞苷来诱导SS患者增加Hb F合成。药物试验取得了成功，但导致这些试验的理论并不正确。另一种理论虽有缺陷，但促使了羟基脲的使用。长期服用该药物可导致Hb F合成显著增加并带来明显的临床益处。目前尚不清楚这种临床益处是真实的还是安慰剂效应。也不完全清楚羟基脲的所有作用都与F细胞生成增加和F/F细胞增加有关。对照临床试验以及对接受治疗患者红细胞特性的研究可能会回答这些问题。它们也很可能不仅会引发其他问题，还可能表明我们目前对镰状细胞病生物学和治疗的理解还远远不够完善。
