Outcome in hemoglobin SC disease: A four-decade observational study of clinical, hematologic, and genetic factors

Over the past 40 years, we observed 284 subjects with hemoglobin SC disease (Hb SC) for 2,837 person-years. We examined the association of the course of clinical events with hematologic and genetic factors. The mean entry age was 21 years, although 15% entered before one year of age. The mean Hb concentration was 11.3 g/dL, the mean fetal hemoglobin was 2.5%, and the mean MCV was 84.4 fL. Twenty-five subjects died at a median age of 37 years. Chronic organ-specific complications occurred In 112 subjects (39.4%), with advanced retinopathy in 65 subjects (22.9%) and osteonecrosis (avascular necrosis) in 42 subjects (14.8%). We identified the P-globin haplotypes in 82 subjects and the a-gene status in 79. Twenty-nine percent had alpha-thalassemia-2. The beta(Cl) haplotype was present in 85.4%. We found a decreased incidence of retinopathy in the beta(Cl) subjects compared to the non-beta(Cl) subjects (33% vs. 67%; P= 0.049) with a later mean onset age (29 years vs. 21 years; log-rank test, P = 0.026). We also found a consistent pattern of decreased morbidity in subjects who had a-thalassemia-2 In comparison to those who did not. We found a reduced risk of chronic organ-specific complications (log-rank test, P = 0.003), lower incidence of sickle crisis (48% vs. 80%, P = 0.001), later onset of gallbladder disease (age of onset: 55 years vs. 34 years; P = 0.055), and lower risk of osteonecrosis (log-rank test, P = 0.024). Our findings suggest that Hb SC subjects who have not inherited a-thalassemia-2 might benefit from erythrocyte rehydration therapy. Am. J. Hematol. 70:206-215, 2002. (C) 2002 Wiley-Liss, Inc.