Sickle Cell Disease
End-Organ Damage Assessment in Sickle Cell Disease
Individuals with sickle cell disease (SCD) are at risk for heart, kidney, lung, and cerebrovascular diseases, and their life expectancy is shorter than that of non-SCD–matched patients. The prevention of end-organ damage, along with aggressive screening and early detection, are critical.
Professor of Pediatrics and Medicine
“It is important to be aggressive when monitoring heart, lung, kidney, and brain function in children and adults with SCD to be better able to make the best use of those treatments that are available to us. Thus, we carefully monitor patients per evidence-based guidelines.”
My philosophy regarding screening and monitoring for end-organ damage is probably more aggressive when compared with some of the approaches outlined in the American Society of Hematology (ASH) 2019 guidelines on cardiopulmonary and kidney diseases in SCD. In the context of detecting pulmonary hypertension, the ASH 2019 guidelines recommend against routine screening with echocardiography in asymptomatic children and adults with SCD. However, cardiopulmonary disease is the main cause of death in adults with SCD. Even if there are no interventions shown in phase 3 clinical trials to improve these factors in patients with SCD, there is value in knowing that a marker of early mortality is present. A 30-year-old patient may want to know how they are doing, and so, cardiac assessment is valuable in this sense. Elevated tricuspid regurgitant jet velocity measurement is among the biomarkers that are most predictive of early death in adults with SCD; brain natriuretic peptide, N-terminal pro-B-type natriuretic peptide levels, and the 6-minute walk test are other valuable assessments.
Similarly, with respect to lung function, the ASH 2019 guidelines suggest that pulmonary function tests should not be done routinely in asymptomatic individuals with SCD. However, lower predicted percentages of forced expiratory volume in 1 second (FEV1) has been associated with earlier mortality in young adults with SCD. Further, although there is currently no therapy to attenuate FEV1 volume loss in SCD, pulmonary function testing is an important biomarker for the adult SCD population because it allows for early intervention to address other respiratory risk factors, such as smoking, that can decrease pulmonary function.
Monitoring renal and cerebrovascular status is also critical. Children with SCD can have glomerular hyperfiltration at as early as ages 2 to 3 years. As they get older, albuminuria develops, so screening for increased albuminuria and creatinine ratio is advisable as soon as a child can reliably void in a cup. The ongoing use of hydroxyurea and a referral to a nephrologist may be warranted. For the brain, the standard of care in all high-income countries is annual transcranial Doppler measurement in children with hemoglobin SS and hemoglobin Sβ0, starting at 2 years of age through 16 years of age, with monthly blood transfusions for at least 1 year. After 1 year, children with no evidence of cerebral vasculopathy based on magnetic resonance angiography (MRA) or silent cerebral infarcts can be offered maximum-tolerated hydroxyurea therapy instead of monthly blood transfusions. If the child does have MRA-defined vasculopathy or silent cerebral infarcts, a transition to hydroxyurea is not recommended.
Unfortunately, despite all of our best treatments, the median life expectancy of patients with SCD is 48 years of age in the modern era. In the adult SCD population, the clustering of end-organ disease is common and multiple organ impairment predicts mortality. Based on the shortened life span of adults with SCD, we carefully monitor heart, lung, kidney, and brain function in children and adults with SCD as per evidence-based guidelines.
Allali S, Taylor M, Brice J, de Montalembert M. Chronic organ injuries in children with sickle cell disease. Haematologica. 2021;106(6):1535-15440. doi:https://doi.org/10.3324/haematol.2020.271353
Chaturvedi S, Ghafuri DL, Jordan N, Kassim A, Rodeghier M, DeBaun MR. Clustering of end-organ disease and earlier mortality in adults with sickle cell disease: a retrospective-prospective cohort study. Am J Hematol. 2018;93(9):1153-1160. doi:10.1002/ajh.25202
DeBaun MR, Ghafuri DL, Rodeghier M, et al. Decreased median survival of adults with sickle cell disease after adjusting for left truncation bias: a pooled analysis. Blood. 2019;133(6):615-617. doi:10.1182/blood-2018-10-880575
DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020;4(8):1554-1588. doi:10.1182/bloodadvances.2019001142
Kassim AA, Payne AB, Rodeghier M, Macklin EA, Strunk RC, DeBaun MR. Low forced expiratory volume is associated with earlier death in sickle cell anemia. Blood. 2015;126(13):1544-1550. doi:10.1182/blood-2015-05-644435
Klings ES, Machado RF, Barst RJ, et al; American Thoracic Society Ad Hoc Committee on Pulmonary Hypertension of Sickle Cell Disease. An official American Thoracic Society clinical practice guideline: diagnosis, risk stratification, and management of pulmonary hypertension of sickle cell disease. Am J Respir Crit Care Med. 2014;189(6):727-740. doi:10.1164/rccm.201401-0065ST
Liem RI, Lanzkron S, Coates TD, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv. 2019;3(23):3867-3897. doi:10.1182/bloodadvances.2019000916
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