Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi‐center study of iron overload

• Published in: American journal of hematology Vol. 82; no. 4; pp. 255 - 265
• Main Authors: Fung, Ellen B., Harmatz, Paul, Milet, Meredith, Ballas, Samir K., De Castro, Laura, Hagar, Ward, Owen, William, Olivieri, Nancy, Smith‐Whitley, Kim, Darbari, Deepika, Wang, Winfred, Vichinsky, Elliott
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2007; Wiley-Liss
• Subjects: Adolescent; Adult; Aged; Anemia, Sickle Cell - complications; Anemia, Sickle Cell - mortality; Anemia, Sickle Cell - therapy; Anemias. Hemoglobinopathies; Biological and medical sciences; Canada - epidemiology; Child; Cohort Studies; Diseases of red blood cells; Erythrocyte Transfusion - adverse effects; Erythrocyte Transfusion - mortality; Female; Ferritins - blood; Hematologic and hematopoietic diseases; Hospitalization; Humans; iron overload; Iron Overload - etiology; Iron Overload - mortality; Male; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Middle Aged; Morbidity; mortality; Other metabolic disorders; sickle cell disease (SCD); thalassemia (Thal); Thalassemia - complications; Thalassemia - mortality; Thalassemia - therapy; United States - epidemiology; Canada; United States; Human; Iron overload; Hemoglobinopathy; Sickle cell anemia; Hematology; Mortality; Metabolic diseases; Thalassemia; Hemopathy; Iron; Morbidity; Genetic disease; Hemolytic anemia
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.20809

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx‐SCD, n = 199), and 64 non‐Tx‐SCD subjects to describe the frequency of iron‐related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 ± 11 years, mean ± SD) and gender (52% female). We found that Tx‐SCD subjects were hospitalized more frequently compared with Thal or non‐Tx‐SCD (P < 0.001). Among those hospitalized, Tx‐SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0–2.5) or non‐Tx‐SCD (RR = 3.1, 95% CI 1.3–7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty‐three deaths were reported (6 Thal, 17 Tx‐SCD) in 23.5 ± 10 months of follow‐up. Within the Tx‐SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx‐SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12–0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow‐up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.