[Sickle cell disease, a genetic haemoglobin disease].

Sickle cell disease is the number one genetic disease in France in terms of the number of children diagnosed each year in the neonatal period. Throughout their lives, people with sickle cell disease are likely to develop acute complications that require urgent treatment. Chronic complications are more common amongst adults than in children.

Polymorphisms in Inflammatory Genes Modulate Clinical Complications in Patients With Sickle Cell Disease.

Sickle cell disease (SCD), the most common monogenic disease worldwide, is marked by a phenotypic variability that is, to date, only partially understood. Because inflammation plays a major role in SCD pathophysiology, we hypothesized that single nucleotide polymorphisms (SNP) in genes encoding functionally important inflammatory proteins might modulate the occurrence of SCD complications. We assessed the association between 20 SNPs in genes encoding Toll-like receptors (TLR), NK cell receptors (NKG), histocompatibility leukocyte antigens (HLA), major histocompatibility complex class I polypeptide-related sequence A (MICA) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), and the occurrence of six SCD clinical complications (stroke, acute chest syndrome (ACS), leg ulcers, cholelithiasis, osteonecrosis, or retinopathy).

An Evaluation of Three Ways of Communicating Carrier Status Results to the Parents of Children in a Neonatal Sickle Cell Screening Programme.

Sickle cell disease (SCD) is the most frequent monogenic disease worldwide; ~5-7% of the world population carry a hemoglobin disorder trait. In the US, one in every 1,941 newborns has SCD, whereas one in every 3,000 newborns in France is affected - resulting in 385 new cases and 5,883 newly identified carriers per year. The objective of the present study was to evaluate three different ways of providing information to parents at risk of having a child with SCD, with a view to increasing the parental screening rate and decreasing the number of new cases per year in France.

A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease.

Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD.

Sickle SCAN™ (BioMedomics) fulfills analytical conditions for neonatal screening of sickle cell disease.

Sickle SCAN™ is a rapid, qualitative, point-of-care lateral flow immunoassay for the identification of AS, AC, SS/Sβthal, SC and CC/Cβthal phenotype. We evaluated this test under the conditions encountered in the French newborn screening (NBS) program for sickle cell disease: a total of 104 dried blood spots (DBSs) were tested with an HPLC reference method and then with the Sickle SCAN™ device. Sickle SCAN™ identified the hemoglobin (Hb) phenotype correctly on 96% of cases.

Renin-angiotensin system blockade promotes a cardio-renal protection in albuminuric homozygous sickle cell patients.

The management of sickle cell nephropathy (SCN) at an early stage is an important issue to prevent renal and cardiovascular morbidity and mortality. This study aimed to evaluate in this population, whether angiotensin converting enzyme inhibitors (ACEIs) treatment could exert a cardio-renal protection in a SCN cohort. Forty-two SCN patients (urine albumin:creatinine ratio (ACR) > 10 mg/mmol) were treated with ACEIs for 6 months, then evaluated for ACR, measured glomerular filtration rate (mGFR) together with haematological and cardiovascular parameters.

Family cord blood banking for sickle cell disease: a twenty-year experience in two dedicated public cord blood banks.

Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks.

Factors predictive of leg-ulcer healing in sickle cell disease: a multicentre, prospective cohort study.

Background: Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking.

Objectives: To determine clinical and biological factors associated with SCD-LU complete healing and recurrence.

Plasma therapy against infectious pathogens, as of yesterday, today and tomorrow.

Plasma therapy consists in bringing to a patient in need - in general suffering a severe, resistant to current therapy, and even lethal infection - plasma or specific, fractioned, antibodies, along with other immunoglobulins and possibly healing factors that can be obtained from immunized blood donors; donors (voluntary and benevolent) can be either actively immunized individuals or convalescent persons. Plasma therapy has been used since the Spanish flu in 1917-1918, and regularly then when viral epidemics threatened vulnerable populations, the last reported occurrence being the 2013-2015 Ebola virus outbreak in West Africa. The precise action mechanism of plasma therapy is not fully delineated as it may function beyond purified, neutralizing antibodies.

Maternal mortality among women with sickle-cell disease in France, 1996-2009.

Objective: To describe maternal mortality among women with sickle-cell disease in France.

Study Design: Data from the national confidential enquiry into maternal deaths and from reference centres for sickle-cell disease were examined to identify women with this disease who died in France during 1996-2009. The maternal mortality ratio among women with sickle-cell disease was estimated and compared with the ratio in the general population.

Prophylactic laparoscopic cholecystectomy in adult sickle cell disease patients with cholelithiasis: A prospective cohort study.

Introduction: Prophylactic laparoscopic cholecystectomy remains controversial and has been discussed for selected subgroups of patients with asymptomatic cholelithiasis who are at high risk of developing complications such as chronic haemolytic conditions. Cholelithiasis is a frequent condition for patients with sickle cell disease (SCD). Complications from cholelithiasis may dramatically increase morbidity for these patients.

[The impact of screening sickle-cell carriers in the general population. A retrospective study in the Paris screening center].

Background: Since 2006 the CIDD, the Paris information and screening center for sickle-cell disease, provides free assistance for adults who may be at risk of having children with sickle-cell disease. Recently, an increasing number of parents of a silent-carrier newborn detected by systematic neonatal screening are attending the center. We present a retrospective study of the impact of such information and screening on people.

Left atrial volume is not an index of left ventricular diastolic dysfunction in patients with sickle cell anaemia.

Background: Left ventricular diastolic dysfunction (LVDD) is common in sickle cell anaemia (SCA). Left atrial (LA) size is widely used as an index of LVDD; however, LA enlargement in SCA might also be due to chronic volume overload.

Aim: To investigate whether LA size can be used to diagnose LVDD in SCA.

Subclinical left ventricular systolic impairment in steady state young adult patients with sickle-cell anemia.

Chronic volume overload in sickle-cell anemia (SCA) is associated with left ventricular (LV) enlargement and hypertrophy. The effect of the disease on LV systolic function remains debated. The aim of our study was to investigate LV systolic function in SCA patients using 2D speckle-tracking imaging.

Sickle-cell disease stroke throughout life: a retrospective study in an adult referral center.

Strokes are one of the most severe complications of sickle-cell disease. Most studies have been restricted to children with sickle-cell disease. To better understand the characteristics and follow-up of strokes occurring from childhood to adulthood, we undertook a retrospective cohort study of 69 stroke patients among the 2,875 patients consulting at the French Adult Sickle-Cell Disease Referral Center.

Outcomes of adult patients with sickle cell disease admitted to the ICU: a case series*.

Objective: Sickle cell disease is associated with a decreased life expectancy, half of the deaths occurring in the ICU. We aimed to describe the characteristics of sickle cell disease patients admitted to ICU and to identify early predictors of a complicated outcome, defined as the need for vital support or death.

Design: Retrospective observational cohort study of sickle cell disease patients over a 6-year period.

Prevalence and correlates of metabolic acidosis among patients with homozygous sickle cell disease.

Background And Objectives: Very few studies report acid base disorders in homozygous patients with sickle cell anemia (SCA) and describe incomplete renal acidosis rather than true metabolic acidosis, the prevalence of which is unknown and presumably low. This study aimed to assess the prevalence of metabolic acidosis and to identify its risk factors and mechanisms.

Design, Setting, Participants, & Measurements: This study retrospectively analyzed 411 homozygous patients with SCA with a GFR ≥ 60 ml/min per 1.

The association of CD81 polymorphisms with alloimmunization in sickle cell disease.

The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization.

High lactate dehydrogenase levels at admission for painful vaso-occlusive crisis is associated with severe outcome in adult SCD patients.

Objectives: The aim of this study is to assess biological prognostic factors at the onset of vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD).

Methods: A monocentric prospective study including all patients admitted for VOC in a reference center for SCD was utilized. We used multivariate logistic regression to find independent predictors of severe evolution, defined by death or a worsening clinical state indicating transfusion or transfer to the intensive care unit.

The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles.

Sickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD.

Hemoglobin sickle cell disease complications: a clinical study of 179 cases.

Background: Hemoglobin sickle cell disease is one of the most frequent hemoglobinopathies. Surprisingly, few studies have been dedicated to this disease, currently considered to be a mild variant of homozygous sickle cell disease. The aim of this study was to update our knowledge about hemoglobin sickle cell disease.

Comparison of CD63 Upregulation Induced by NSAIDs on Basophils and Monocytes in Patients with NSAID Hypersensitivity.

Background. An in vitro basophil activation test, based on the detection of CD63 upregulation induced by NSAIDs, has been described. Its clinical significance remains controversial.