Sickle Cell Disease (SCD)


Sickle cell disease (SCD) is an inherited hemoglobin disorder. The abnormal hemoglobin causes red blood cells (RBCs) to deform into a sickle shape, which results in premature death of the RBCs, interruption of blood flow, damage to multiple tissues and organs, and an increased risk for early death. Improvements in interventions made during recent years have made it possible to treat complications more effectively and have decreased mortality in pediatric patients, so that currently 95% of children with SCD reach 18 years of age.1,2

Overall, the life expectancy of patients with SCD is lower than that of persons without SCD.1 Life expectancy may vary depending on the type of disease, the treatments administered, and the complications that arise during the course of the disease.

Low Life Expectancy with Sickle Cell Disease

Owing to the hemolysis and vascular damage caused by sickle RBCs, most patients with SCD experience long-term morbidities and complications, such as vaso-occlusive crises, acute chest syndrome, stroke, silent infarcts, renal failure, and pulmonary hypertension. Thus, their life expectancy is reduced compared with that of the general population. A recent study estimated the life expectancy of adults with SCD to be 54 years, which is approximately 20 years shorter than that of normal adults without SCD.1 Although new treatments and optimal disease management have improved the life expectancy of persons with SCD, with patients now surviving beyond the age of 50 years, their life expectancy is still shorter than that of the general population.

Life Expectancy Improvements with Sickle Cell Disease

The life expectancy of patients with SCD has improved greatly in high-income countries during the last few decades. Previously, in the 1960s, SCD was known as a “disease of childhood” because of the high mortality rate among children with the disease.3 A study conducted 25 years later, the Cooperative Study of Sickle Cell Disease, reported that 85% of patients with hemoglobin SS (HbSS) survived to adulthood.4 The current estimate is that 94% of patients in the United States, 97% in Paris, and 99% in London survive to adulthood.5

In 1994, the median survival of patients with the genotype HbSS or HbSβ0 (sickle beta zero thalassemia) was estimated to be 42 to 48 years; this increased to 58 years in the United States by 2014.4 The dramatic improvement in the survival of patients with SCD can be attributed to interventions such as newborn screening, the prophylactic use of antibiotics (penicillin), primary stroke prevention with transcranial Doppler screening, hydroxyurea treatment, and effective vaccinations against infection with Haemophilus influenzae type b or Streptococcus pneumoniae.6

Despite the improved survival of adults with SCD, their life expectancy is shorter than that of the general population by about 20 years, and their quality of life is often poor. These issues are likely due to high medical costs, lack of access to high-quality care, and the lack of treatments for long-term complications.1

Risk Factors for Early Death in Sickle Cell Disease

Several disease features have been found to be associated with an increased risk for death6 in patients with SCD, including elevated tricuspid regurgitant jet velocity (TRV) on echocardiography,7 pulmonary hypertension,8 elevated levels of N-terminal pro-brain natriuretic peptide (NT-pro-BNP),9 history of asthma,10 end-stage renal disease requiring dialysis,11 severe hemolysis,12 and prolongation of the QTc interval.13

References

  1. Lubeck D, Agodoa I, Bhakta N, et al. Estimated life expectancy and income of patients with sickle cell disease compared with those without sickle cell disease. JAMA Netw Open. 2019;2(11):e1915374. doi:10.1001/jamanetworkopen.2019.15374
  2. Fingar KR, Owens PL, Reid LD, Mistry KB, Barrett ML. Characteristics of inpatient hospital stays involving sickle cell disease, 2000–2016: statistical brief #251. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Accessed November 25, 2021.
  3. Dacie J. The hereditary haemoglobinopathies. In: Sickle Cell Disease and Allied Syndromes. The Haemolytic Anaemias: Congenital and Acquired Part I—The Congenital Anaemias. New York, NY: Grune & Stratton; 1958:243-330.
  4. Gardner K, Douiri A, Drasar E, et al. Survival in adults with sickle cell disease in a high-income setting. Blood. 2016;128(10):1436-1438. doi:10.1182/blood-2016-05-716910
  5. Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115(17):3447-3452. doi:10.1182/blood-2009-07-233700
  6. Maitra P, Caughey M, Robinson L, et al. Risk factors for mortality in adult patients with sickle cell disease: a meta-analysis of studies in North America and Europe. Haematologica. 2017;102(4):626-636. doi:10.3324/haematol.2016.153791
  7. Ataga KI, Moore CG, Jones S, et al. Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol. 2006;134(1):109-115. doi:10.1111/j.1365-2141.2006.06110.x
  8. Mehari A, Alam S, Tian X, et al. Hemodynamic predictors of mortality in adults with sickle cell disease. Am J Respir Crit Care Med. 2013;187(8):840-847. doi:10.1164/rccm.201207-1222OC
  9. Machado RF, Anthi A, Steinberg MH, et al. N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease. JAMA. 2006;296(3):310-318. doi:10.1001/jama.296.3.310
  10. Boyd JH, Macklin EA, Strunk RC, DeBaun MR. Asthma is associated with increased mortality in individuals with sickle cell anemia. Haematologica. 2007;92(8):1115-1118. doi:10.3324/haematol.11213
  11. McClellan AC, Luthi JC, Lynch JR, et al. High one year mortality in adults with sickle cell disease and end-stage renal disease. Br J Haematol. 2012;159(3):360-367. doi:10.1111/bjh.12024
  12. Nouraie M, Lee JS, Zhang Y, et al. The relationship between the severity of hemolysis, clinical manifestations and risk of death in 415 patients with sickle cell anemia in the US and Europe. Haematologica. 2013;98(3):464-472. doi:10.3324/haematol.2012.068965
  13. Upadhya B, Ntim W, Brandon Stacey R, et al. Prolongation of QTc intervals and risk of death among patients with sickle cell disease. Eur J Haematol. 2013;91(2):170-178. doi:10.1111/ejh.12127

Reviewed by Debjyoti Talukdar, MD, on 11/28/2021.

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