CORE--Inter Center Collaborative Clinical Research

出生时，大约每830名非裔美国人中就有1人患有HbSC疾病。这些患者具有与镰状细胞性贫血相同的血管闭塞性并发症，只是发生率较低。HbSC疾病的临床描述比比皆是，并对其独特的病理生理学有了实质性的了解。然而，很少有关于其治疗的公开试验存在。也许这是HbSC疾病是良性的错误观念的线索，或者它的罕见性妨碍了结论性的治疗试验。我们认为：HbSC疾病并发症通常需要急性治疗；一种安全的预防性治疗可以预防随着年龄增长而出现的疾病并发症；逆转这种疾病的病理生理学的新方法是可用的；有足够的病人来进行成功的治疗试验。HbSC疾病表现为特征性的红细胞脱水

At birth, about 1 in 830 African Americans has HbSC disease. These patients have the same vasoocclusive complications as sickle cell anemia---only less often. Clinical descriptions of HbSC disease abound and substantial insights into its distinct pathophysiology have been gained. Nevertheless, few published trials of its treatment exist. Perhaps this is clue to the mistaken perception that HbSC disease is benign or that its rarity precludes conclusive therapeutic trials. We submit that: HbSC disease complications often merit acute treatment; a safe preventive treatment might forestall the disease complications that develop with age; novel means of reversing the pathophysiology of this disorder are available; sufficient patients exist to carry out a successful therapeutic trial. HbSC disease exhibits a characteristic erythrocyte dehydration compared with sickle cell trait or HbC trait erythrocytes. Cell dehydration plays a crucial role in the pathophysiology of HbSC disease because it allows for the intracellular HbS to reach concentrations that induce clinically significant HbS polymerization and cell sickling. K-CI cotransport is highly expressed in HbSC erythrocytes and determines their characteristic microcytosis and dehydration. Thus, HbSC disease represents the ideal target for therapies aimed at preventing K-CI cotransport mediated cell dehydration. Pilot studies showed that hydroxyurea and Mg affect erythrocyte hydration in HbSC disease. Our hypothesis is that oral Mg and hydroxyurea will increase intracellular Mg, block K-CI cotransport, prevent cell dehydration, and reduce polymerization-induced vasoocclusive complications. Accordingly, we propose a double-blinded, placebo-controlled trial to examine the effectiveness of hydroxyurea, magnesium pidolate and hydroxyurea + magnesium pidolate in reducing cell density in HbSC disease. As a secondary endpoint, because of the required brevity of this trial, we will examine the effectiveness of this treatment in preventing sickle cell disease-related vasoocclusive episodes. Other secondary endpoints include HbF level, F-cell numbers and hematologic measurements. The cellular effects of hydroxyurea and magnesium should modulate favorably the course of this disorder and the results of this study will provide the framework for a definitive efficacy trial.