Sickle cell disease Ware, Russell E, Dr Prof; de Montalembert, Mariane, MD PhD; Tshilolo, Léon, Prof ...
The Lancet (British edition),
07/2017, Volume:
390, Issue:
10091
Journal Article
Peer reviewed
Summary Sickle cell disease is a common and life-threatening haematological disorder that affects millions of people worldwide. Abnormal sickle-shaped erythrocytes disrupt blood flow in small ...vessels, and this vaso-occlusion leads to distal tissue ischaemia and inflammation, with symptoms defining the acute painful sickle-cell crisis. Repeated sickling and ongoing haemolytic anaemia, even when subclinical, lead to parenchymal injury and chronic organ damage, causing substantial morbidity and early mortality. Currently available treatments are limited to transfusions and hydroxycarbamide, although stem cell transplantation might be a potentially curative therapy. Several new therapeutic options are in development, including gene therapy and gene editing. Recent advances include systematic universal screening for stroke risk, improved management of iron overload using oral chelators and non-invasive MRI measurements, and point-of-care diagnostic devices. Controversies include the role of haemolysis in sickle cell disease pathophysiology, optimal management of pregnancy, and strategies to prevent cerebrovascular disease.
Several adult studies have shown that sickle cell disease is associated with cardiac abnormalities and premature death. The aim of this study was to use speckle-tracking strain, a relatively load ...independent parameter, to evaluate systolic left ventricular (LV) and right ventricular (RV) function in a pediatric sickle cell disease population.
Twenty-eight patients with sickle cell disease (mean age, 10.0 ± 3.6 years; mean body surface area, 1.14 ± 0.27 m(2)) and 29 controls matched for age and body surface area were compared. Cardiac output, LV dimension, wall thickness and circumferential strain, LV and RV longitudinal systolic strain, conventional and tissue Doppler parameters, and pulmonary pressure were assessed.
LV cardiac output was significantly higher in patients, as were indexed LV systolic diameter, indexed LV mass, and E/E' septal ratio. Indexed LV diastolic diameter, wall thickness, LV shortening fraction, and global LV longitudinal and circumferential strains were similar in patients and controls. However, their global RV longitudinal strain was significantly lower, although tricuspid annular plane systolic excursion and color-coded tricuspid S-wave velocity were similar. Among patients, 21% had tricuspid regurgitation velocities > 2.5 m/sec, but none had tricuspid regurgitation velocities > 3 m/sec. Indexed LV diastolic dimension and systolic pulmonary artery pressure were significantly higher in patients whose hemoglobin was <80 g/L, but parameters of systolic and diastolic LV function were similar.
In children with sickle cell disease, LV diastolic function is significantly altered, although LV systolic function, evaluated by global longitudinal strain, is normal. In addition, cardiac output is increased, and elevated tricuspid regurgitation velocity is common, whereas it is never found in controls. Most importantly, global RV longitudinal systolic strain is significantly altered.
A 13-year-old girl with homozygous sickle cell disease was referred for vision loss in her left eye of 1 year's duration. Clinical findings were consistent with a past retinal arterial occlusion. In ...the asymptomatic right eye, spectral domain optical coherence tomography showed a severe atrophy of the inner retinal layers of the temporal median raphe; a significant internal carotid stenosis was also present. We hypothesize that specific atrophy of the retinal temporal median raphe resulted from chronic ischemia. The inner layers of the retina are vascularized by terminal vessels and the median raphe can therefore be regarded as a junction territory; its atrophy may represent an ocular equivalent of a silent border zone cerebral infarct.
Pyruvate kinase (PK) deficiency is asymptomatic in heterozygotes, but it can lead in homozygous neonates to a severe neonatal hemolysis, sometimes life-threatening. We report five cases, with a 1- to ...17-month delayed diagnosis, highlighting the need to measure PK activity in neonates and parents in case of an hemolysis at birth.
