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 beta-globin haplotypes in 82 subjects and the alpha-gene status in 79. Twenty-nine percent had alpha-thalassemia-2. The beta(CI) haplotype was present in 85.4%. We found a decreased incidence of retinopathy in the beta(CI) subjects compared to the non-beta(CI) 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 alpha-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 alpha-thalassemia-2 might benefit from erythrocyte rehydration therapy.
Department of Pediatrics, Division of Hematology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA. powars@hsc.usc.edu
Darleen R
DR
Powars
Alan
A
Hiti
Emily
E
Ramicone
Cage
C
Johnson
Linda
L
Chan
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004909:Erythrocyte Indices; D005128:Eye Diseases / Q000150:complications; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics; D006239:Haplotypes; D006450:Hemoglobin SC Disease / Q000097:blood* / Q000150:complications / Q000235:genetics* / Q000401:mortality; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009017:Morbidity; D010020:Osteonecrosis / Q000150:complications; D016133:Polymerase Chain Reaction; D017085:alpha-Thalassemia / Q000235:genetics
D006454:Hemoglobins; D005914:Globins; D005319:Fetal Hemoglobin