Early splenectomy in a large cohort of children with sickle cell anemia: risks and consequences

In children with sickle cell anemia (SCA), early splenic complications can require splenectomy, but the benefit-to-risk ratio and the age at which splenectomy may be safely performed remain unclear. To address this question, we analyzed the rate of post-splenectomy events in children with SCA splenectomized between 2000-2018 at the Robert Debré University Hospital, Paris, France. A total of 188 children underwent splenectomy, including 101 (11.9%) from our newborn cohort and 87 referred to our center. Median (Q1-Q3) age at splenectomy was 4.1 years (range 2.5-7.3 years), with 123 (65.4%) and 65 (34.6%) children splenectomized at ≥3 years of age or <3 years of age, respectively. Median postsplenectomy follow-up was 5.9 years (range 2.7-9.2 years) yielding 1192.6 patient-years (PY) of observation. Indications for splenectomy were mainly acute splenic sequestration (101 [53.7%]) and hypersplenism (75 [39.9%]). All patients received penicillin prophylaxis; 98.3% received 23-valent polysaccharic pneumococcal (PPV-23) vaccination, and 91.9% a median number of 4 (range 3-4) pneumococcal conjugate vaccine shots prior to splenectomy. Overall incidence of invasive bacterial infection and thrombo-embolic events were 0.005 / PY (no pneumococcal infections) and 0.003 / PY, respectively, regardless of age at splenectomy. There was an increased proportion of children with cerebral vasculopathy in children splenectomized <3 years of age (0.037 / PY vs. 0.011 / PY; P<0.01). A significantly greater proportion of splenectomized than non-splenectomized children were treated with hydroxycarbamide (77.2% vs. 50.1%; P<0.01), suggesting a more severe phenotype in children who present spleen complications. If indicated, splenectomy should not be delayed in children, provided recommended pneumococcal prophylaxis is available. Spleen complications in childhood may serve as a marker of severity

Stroke without cerebral arteriopathy in sickle cell disease children: causes and treatment

Cerebral arteriopathy (CA) in children with sickle cell disease (SCD) is classically described as chronic stenosis of arteries in the anterior brain circulation, leading to ischemic stroke. Some studies have however reported strokes in children with SCD but without CA. In order to better understand the etiology and risk factors of these strokes, we retrospectively analyzed ischemic strokes occurring in a large cohort of children over a 13 year-period. Between 2007 and 2020, 25/1500 children with SCD had an ischemic stroke in our center. Among them, 13 (52%) had CA, described as anatomical arterial stenosis, while 12 (48%) did not. Patients with stroke without CA were older than patients with stroke attributed to SCD-CA (9.0 years old vs 3.6 years old, p=0.008), and had more frequently a SC genotype (25% vs 0% respectively). Their stroke involved posterior circulation more frequently, with cerebellar involvement in 42%. Retained stroke etiologies in patients without typical SCD-related CA were reversible cerebral vasoconstriction syndrome, cerebral fat embolism, arterial thrombosis or thromboembolism, hyperviscosity, vasculitis in a context of infectious meningoencephalitis, and severe hemodynamic failure. No recurrence was observed in the 24 months following stroke, even though 67% of the patients were no longer receiving exchange transfusions in this group. In conclusion, in a cohort of pediatric SCD patients with efficient stroke screening strategy, half of occurring ischemic strokes were related to causes other than CA. They affected a different population of SCD children and systematic long-term transfusion programs may not be necessary in these cases

Pubertal development of transfusion-dependent thalassemia patients in the era of oral chelation with deferasirox: results from the French registry

Not available

Tolerance and humoral immune response to the yellow fever vaccine in sickle cell disease children treated with hydroxyurea: a multicentre prospective study

International audienceBackgroundSickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU.MethodSCD children < 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination.ResultsAmong the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5–8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines.ConclusionYF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU

Effect of transfusion therapy on cerebral vasculopathy in children with sickle-cell anemia

This study emphasizes the wide heterogeneity of the course of cerebral vasculopathy in children with sickle-cell anemia on regular transfusion protocol

Evaluation of Outcomes and Quality of Care in Children with Sickle Cell Disease Diagnosed by Newborn Screening: A Real-World Nation-Wide Study in France

This study’s objective was to assess, on a national scale, residual risks of death, major disease-related events, and quality of care during the first five years in children diagnosed at birth with sickle cell disease (SCD). Data were retrospectively collected from medical files of all children with SCD born between 2006–2010 in France. Out of 1792 eligible subjects, 1620 patients (71.8% SS or S/beta°-thalassemia -SB°-) had available follow-up data, across 69 centers. Overall probability of survival by five years was 98.9%, with 12/18 deaths related to SCD. Probability of overt stroke by five years in SS/SB° patients was 1.1%, while transcranial Doppler (TCD) was performed in 81% before three years of age. A total of 26 patients had meningitis/septicemia (pneumococcal in eight cases). Prophylactic penicillin was started at a median age of 2.2 months and 87% of children had received appropriate conjugate pneumococcal vaccination at one year. By five years, the probability of survival without SCD-related events was 10.7% for SS/SB° patients. In contrast, hydroxyurea was prescribed in 13.7% and bone marrow transplant performed in nine patients only. In this study, residual risks of severe complications were low, probably resulting from a good national TCD, vaccination, and healthcare system coverage. Nonetheless, burden of disease remained high, stressing the need for disease-modifying or curative therapy

Anti-C5 antibody treatment for delayed hemolytic transfusion reactions in sickle cell disease

International audienceDelayed hemolytic transfusion reaction (DHTR) is an unpredictable severe complication of transfusion in patients with sickle cell disease (SCD). It presents clinically as a vaso-occlusive crisis (VOC), often associated with the failure of one or more organs, after the transfusion of packed red blood cells (pRBC).1,2 Hyperhemolysis is encountered in the most severe forms. Both transfused and autologous red blood cells (RBC) are lysed.The mechanisms underlying DHTR remain unclear. Alloantibodies against RBC antigens were initially thought to underlie the pathophysiology, but no such antibodies are detected in about a third of the cases.3RBC degradation products, such as hemoglobin and heme, are released into the bloodstream during intravascular hemolysis. These elements and heme-loaded membrane microvesicles have recently been implicated in inflammation and organ injury in DHTR.4 Complement is activated via the classical pathway, by alloantibodies, and/or via the alternative pathway, by free heme.5 Hemedependent complement deposits on the endothelium contribute to organ damage.6 Due to these vascular lesions, hyperhemolysis often progresses to multiple organ failure and, in some cases, death