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Mortality in sickle cell disease. Life expectancy and risk factors for early death

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Platt, Orah S., Brambilla, Donald J., Rosse, Wendell F., Milner, Paul F., Castro, Oswaldo, Steinberg, Martin H., Klug, Panpit P.·1994·New England Journal of Medicine
DOI 10.1056/nejm199406093302303
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Abstract

BACKGROUND: Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-beta-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 the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. RESULTS: Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling 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 hemoglobin 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 chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy.

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  • Higher fetal hemoglobin levels are linked to lower morbidity and mortality in TDT and SCD.

    “Elevated levels of fetal hemoglobin (consisting of two alpha and two gamma chains) are associated with improved morbidity and mortality in patients with TDT and SCD.[20][21][22]”

    From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [21]

    The Risk Factors for Early Death section (p. 4) links higher fetal hemoglobin to lower mortality in patients with sickle cell anemia, and the Discussion (p. 6) reports improved life expectancy. The paper does not establish that association for transfusion-dependent thalassemia (TDT), or link fetal hemoglobin levels to improved morbidity. (LLM, conf=0.88)

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  • The presence of chronic kidney disease is an independent predictor of pulmonary vascular disease and early mortality in adults with sickle cell disease.

    “the presence of chronic kidney disease is an independent predictor of pulmonary vascular disease and early mortality in adults with SCD (68, 202).”

    From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [68]

    Table 5 (p. 6) identifies renal failure as a risk factor for early death in a multivariate model of adults with sickle cell anemia. It does not assess whether chronic kidney disease independently predicts pulmonary vascular disease; the Circumstances of Death section (p. 3) says the study had no working definition of chronic pulmonary failure. (LLM, conf=0.90)

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  • In 3764 patients in the pre-hydroxyurea era, HbF greater than 8.6% was associated with improved survival.

    “In 3764 patients in the pre-hydroxyurea era, HbF .8.6% was associated with improved survival.60”

    From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [60]

    The Survival section (p. 2) reports improved survival for patients with sickle cell anemia whose fetal hemoglobin exceeded 8.6%. The Methods (pp. 1–2) say more than 3,764 patients were enrolled in the broader study, but the survival comparison and risk-factor models used smaller groups; the claim incorrectly presents 3,764 as the number in the HbF analysis. Our copy does not explicitly establish the 'pre-hydroxyurea era' qualifier. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Patients affected by sickle cell anemia and β-thalassemia experience a milder course of the disease if they express elevated levels of fetal hemoglobin in adulthood.

    “Patients affected by sickle cell anemia and β-thalassemia experience a milder course of the disease if they express elevated levels of fetal hemoglobin in adulthood (Platt et al., 1994; Weatherall, 2001).”

    From Reactivation of developmentally silenced globin genes by forced chromatin looping (2014) · cites this paper as Platt et al., 1994

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Research works printed but not linked: 2

  1. [2]2. Diggs LM. Anatomic lesions in sickle cell disease. In: Abramson H, Bertles JF, Wethers DL, eds. Sickle cell disease: diagnosis, management, education, and research. St. Louis: C.V. Mosby, 1973:189-229.
  2. [11]11. Dixon WJ, ed. BMDP statistical software manual. Vol. 2. Berkeley: Unis versity of California, 1992.

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Authors
Platt, O. S., Brambilla, D. J., Rosse, W. F., Milner, P. F., Castro, O., Steinberg, M. H., & Klug, P. P.
Affiliations
  • Boston Children's Hospital (US)
  • New England Research Institutes (US)
  • Duke University (US)
  • Augusta University (US)
  • Howard University (US)
  • University of Mississippi Medical Center (US)
  • Texas Tech University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1994-06-09
Volume
330
Issue
23
Pages
1639-1644
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199406093302303
OpenAlex
W2334263927
Semantic Scholar
6bcc7a4d436214c41a4d128f9d221e950eb4962b
Cited by
3,320
References
19
Citations by year
2026: 83 · 2025: 104 · 2024: 123 · 2023: 135 · 2022: 128 · 2021: 167 · 2020: 147 · 2019: 168 · 2018: 140 · 2017: 159 · 2016: 173 · 2015: 165 · 2014: 154 · 2013: 139 · 2012: 115
FWCI
24.43
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Howard (Howard University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
Keywords
sickle cell disease, sickle cell-hemoglobin C disease, sickle beta-thalassemia, life expectancy, mortality risk factors, acute chest syndrome, vaso-occlusive crisis, stroke, renal failure, seizures, fetal hemoglobin, white blood cell count, organ failure
MeSH terms
Adult, Aged, Anemia, Sickle Cell, Cause of Death, Child, Female, Hemoglobin SC Disease, Humans, Life Expectancy, Male, Middle Aged, Probability, Regression Analysis, Risk Factors, Survival Analysis, beta-Thalassemia

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