MORTALITY IN SICKLE-CELL DISEASE - LIFE EXPECTANCY AND RISK-FACTORS FOR EARLY DEATH

Background. Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sic kle cell-hemoglobin C disease, and the sickle cell-P-thalassemias) is needed to counsel patients, target therapy, and design clinical trials . Methods. We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate t he median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and us ed proportional-hazards regression analysis to identify risk factors f or early death among 964 adults with sickle cell anemia who were follo wed for at least two years. Results. Among children and adults with si ckle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those wi th sickle cell-hemoglobin C disease, the median age at death was 60 ye ars for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt orga n failure, predominantly renal. Thirty-three percent were clinically f ree of organ failure but died during an acute sickle crisis (78 percen t had pain, the chest syndrome, or both; 22 percent had stroke). Model ing revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobi n were associated with an increased risk of early death. Conclusions. Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chroni c organ failure but died during an acute episode of pain, chest syndro me, or stroke. Early mortality was highest among patients whose diseas e was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult lif e expectancy.