Steinberg M H, Rosenstock W, Coleman M B, Adams J G, Platica O, Cedeno M, Rieder R F, Wilson J T, Milner P, West S
Blood. 1984 Jun;63(6):1353-60.
The characteristic clinical heterogeneity of sickle cell anemia (HbSS) may be, in part, a result of its interactions with alpha-thalassemia. Although alpha-thalassemia clearly affects some hematologic features of HbSS, its role in modulating the vasoocclusive severity of disease is not clear. To further explore this relationship, we examined the incidence of painful episodes, acute chest syndrome, aseptic bone necrosis, and leg ulcers in 3 patient groups with sickle cell disease: (1) 2,147 patients over age 2 yr, stratified according to mean corpuscular volume (MCV); (2) 183 patients selected on the basis of microcytosis and elevated HbA2, on whom globin biosynthesis studies were done; and (3) 125 patients who had alpha-globin genotype assigned by restriction endonuclease gene mapping. When patients were stratified by MCV, there was a reciprocal relationship between HbA2 levels and MCV, reflecting the presence of patients with beta o and alpha-thalassemia in the low MCV groups. The erythrocyte indices and HbA2 levels in patients classified as HbSS-alpha-thalassemia, by either globin synthesis studies or gene mapping, were very similar to those previously reported by others. Neither microcytosis, beta o, or alpha-thalassemia appeared to provide any clear protection from the vasoocclusive complication evaluated, and the prevalence of aseptic necrosis was increased in patients with microcytosis over age 20 yr and in groups with alpha-thalassemia. The effects of a reduced MCV and mean corpuscular hemoglobin concentration (MCHC), of possible benefit by themselves, when accompanied by a reduction in hemolysis and rise in hemoglobin concentration, as in HbSS-alpha-thalassemia, may cause sufficient rise in blood viscosity in critical vascular beds to impair blood flow and negate any amelioration of vasoocclusive complications in HbSS.
镰状细胞贫血（HbSS）具有特征性的临床异质性，部分原因可能是其与α地中海贫血相互作用的结果。尽管α地中海贫血明显影响HbSS的一些血液学特征，但其在调节疾病血管闭塞严重程度方面的作用尚不清楚。为了进一步探究这种关系，我们研究了3组镰状细胞病患者的疼痛发作、急性胸综合征、无菌性骨坏死和腿部溃疡的发生率：（1）2147名2岁以上患者，根据平均红细胞体积（MCV）分层；（2）183名基于小红细胞症和HbA2升高入选的患者，对其进行了珠蛋白生物合成研究；（3）125名通过限制性内切酶基因图谱确定α珠蛋白基因型的患者。当患者按MCV分层时，HbA2水平与MCV呈反比关系，这反映了低MCV组中存在βo和α地中海贫血患者。通过珠蛋白合成研究或基因图谱分类为HbSS-α地中海贫血的患者，其红细胞指数和HbA2水平与其他人先前报道的非常相似。小红细胞症、βo或α地中海贫血似乎都不能为所评估的血管闭塞并发症提供明确的保护，20岁以上小红细胞症患者和α地中海贫血组的无菌性坏死患病率增加。在HbSS-α地中海贫血中，MCV和平均红细胞血红蛋白浓度（MCHC）降低本身可能有益，同时伴有溶血减少和血红蛋白浓度升高，这可能会使关键血管床中的血液粘度充分升高，从而损害血流，并抵消HbSS中血管闭塞并发症的任何改善。
