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Chronic organ injuries in children with sickle cell disease
Ferrata Storti Foundation
Haematologica 2021 Volume 106(6):1535-1544
Slimane Allali,1,2,3 Melissa Taylor,1,3,4 Joséphine Brice1,3,5 and Mariane de Montalembert1,3,5
1Department of General Pediatrics and Pediatric Infectious Diseases, Reference Center for Sickle Cell Disease, Necker Hospital for Sick Children, Assistance Publique – Hôpitaux de Paris (AP-HP), Université de Paris, Paris; 2Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Université de Paris, Imagine Institute, Inserm U1163, Paris; 3Laboratory of Excellence GR-Ex, Paris; 4Paris-Cardiovascular Research Centre (PARCC), Université de Paris, Inserm U970, Paris and 5Institut National de la Transfusion Sanguine (INTS), Université de Paris, Inserm U1134, Paris, France
ABSTRACT
Median life expectancy of patients with sickle cell disease has increased to up to 55 years but there are still frequent cases of pre- mature death, mostly in patients with pre-existing organ failure such as pulmonary hypertension, kidney injury, and cerebral vasculopathy. Most organ injuries remain asymptomatic for a long time and can only be detected through early systematic screening. Protocols combining assessment of velocities on transcranial Doppler and regular transfusions in patients with abnormal velocities have been demonstrated to dramatically reduce the risk of stroke. In contrast, no consensus has been reached on systematic screening or therapy for silent cerebral infarcts. The prognostic significance of increased tricuspid regurgitant jet velocity on echocardiography has not yet been iden- tified in children, whereas increased albuminuria is a good predictor of kid- ney injury. Finally, screening for hip and eye disorder is recommended; how- ever, different countries adopt different screening strategies. Hydroxyurea is probably of potential benefit in preventing chronic organ damage but this requires further study in order to be fully demonstrated. Efficacy and safety of the other new drugs available are also under investigation.
Introduction
In high-income countries, >98% of children affected by sickle cell disease (SCD) reach adulthood, and the disease has shifted from being a fatal illness in children to a chronic disease with multiple organ dysfunction in adults.1-4 Median life expectan- cy has increased to up to approximately 55 years,4-8 which remains far below the life expectancy of ethnicity-matched non-SCD controls.4 Fatalities mostly occur in patients with pre-existing organ failure, such as kidney injury, cerebral vasculopa- thy, and pulmonary hypertension.7,8 Most organ injuries remain asymptomatic for several decades and can only be detected through early systematic screening. Identification of early predictors of organ damage could help guide the initiation of specific treatments for the injured organ, prevent secondary worsening, and opti- mize SCD management. To date, increased velocities on transcranial Doppler in children and elevated tricuspid regurgitant jet velocity in adults are the only vali- dated predictors of risk of stroke and death, respectively.9,10 Biological predictors of severity are mostly limited to hemolysis markers, and have weak individual predic- tive values.5,11-15 There is still no genetic signature of severity robust enough to pre- dict individual outcome.16 Thus, regular screening for early signs of organ dysfunc- tion appears to be the best strategy for the prevention of secondary organ failure and early mortality. In this review, we describe the main chronic organ dysfunc- tions reported in children with SCD and propose a checklist of screening tests.
Pathophysiology of chronic organ injury
SCD originates from the sickle mutation on the HBB gene (Glu6Val, bS), the most common and severe form being homozygous HbSS. Other forms of SCD
Correspondence:
MARIANE DE MONTALEMBERT
mariane.demontal@nck.aphp.fr
Received: September 25, 2020. Accepted: November 6, 2020. Pre-published: February 25, 2021.
https://doi.org/10.3324/haematol.2020.271353
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