Red blood cell (RBC) transfusion is a major therapy for sickle cell disease (SCD). Patients are at risk of forming antibodies to RBC antigens, which can result in the impossibility to find compatible units and can cause hemolytic transfusion reactions. This retrospective study investigates the evolution of RBC consumption and the frequencies, specificities, and chronology of the appearance of antibodies in a population of patients consistently receiving RH (C, D, E, c, e) and K–matched RBC units (RBCus) from a predominantly European donor population. Over the 11-year period in the Paris area, 6496 patients received transfusion at least once for a total of 239 944 units. Antibodies were made by 1742 patients. The first antibodies of a patient were predictive of subsequent immunization. By the 17th RBCu transfused (by the 20th, excluding warm autoantibodies), 75% of the patients who would make antibodies had made their first. By the 16th, 90% who would make antibodies to a high frequency antigen had made their first antibody to these antigens. Females made their first antibodies slightly earlier than males. Patients who received multiple transfusions (>50 units) had a higher immunization prevalence than those who rarely received transfusion (<12 units) but fewer clinically significant antibodies. Patients with SCD and prophylactic RH-K matching not immunized by the 20th RBCu are likely to have a low alloimmunization risk (to antigens other than RH-K), that is, be low responders, especially relative to the most clinically significant antibodies. This number of 20 units is a point before which close monitoring of patients is most important but remains open to future adjustment.

Sickle cell disease (SCD) refers to a group of inherited hemoglobin disorders in which sickle red blood cells display altered deformability, leading to a significant burden of acute and chronic complications, such as vaso-occlusive pain crises (VOCs). Hydroxyurea is a major therapeutic agent in adult and pediatric sickle cell patients. This treatment is an alternative to transfusion in some complications. Indeed, it increases hemoglobin F and has an action on the endothelial adhesion of red blood cells, leukocytes, and platelets. Although the safety profile of hydroxyurea (HU) in patients with sickle cell disease has been well established, the existing literature on HU exposure during pregnancy is limited and incomplete. Pregnancy in women with SCD has been identified as a high risk for the mother and fetus due to the increased incidence of maternal and non-fetal complications in various studies and reports. For women on hydroxyurea at the time of pregnancy, transfusion therapy should probably be initiated after pregnancy. In addition, there is still a significant lack of knowledge about the incidence of pregnancy, fetal and maternal outcomes, and management of pregnant women with SCD, making it difficult to advise women or clinicians on outcomes and best practices. Therefore, the objective of this study was to describe pregnancy outcomes (n = 128) reported in the noninterventional European Sickle Cell Disease COhoRT-HydroxyUrea (ES-CORT-HU) study. We believe that our results are important and relevant enough to be shared with the scientific community.

Hydroxyurea (HU) is useful for treating sickle cell anemia because of its ability to reduce some of the severe clinical events such as painful crises and acute chest syndrome. It may also reduce the need for blood transfusions and frequent hospitalizations and reduce mortality. Nevertheless, no consistent recommendations regarding its therapeutic schedule are defined. Our aim was to improve and validate a high performance liquid chromatography (HPLC) technique to measure HU and to study HU levels in serum and urine of sickle cell anemia patients and relate this to treatment efficacy and compliance. Thirty-seven patients received 1,128 +/- 333 mg of HU per day (8.0 to 28.0 mg/kg/day). Plasma and/or urine were sampled and HU was measured using an HPLC method coupled with UV detection. We validated a specific, sensitive assay with good reproducibility and linearity, and showed a positive relationship between plasma HU concentrations and time elapsed between oral HU intake and sampling. We observed plasma HU concentrations were positively correlated with change in mean corpuscular volume (MCV) before and during the treatment. No correlation was obtained between HU concentration and Hb F level.

Sudden death is 1 of the leading causes of death in adults with sickle cell anemia (SCA) but its etiology remains mostly unknown. Ventricular arrhythmia (VA) carries an increased risk of sudden death; however, its prevalence and determinants in SCA are poorly studied. This study aimed to identify the prevalence and predictors of VA in patients with SCA. From 2019 to 2022, 100 patients with SCA were referred to the physiology department to specifically analyze cardiac function and prospectively included in the DREPACOEUR registry. They underwent a 24-hour electrocardiogram monitoring (24h-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of VA, defined as sustained or nonsustained ventricular tachycardia (VT), >500 premature ventricular contractions (PVCs) on 24h-Holter, or a recent history of VT ablation. The mean patient age was 46 ± 13 years, and 48% of the patients were male. Overall, VA was observed in 22 (22%) patients. Male sex (81% vs 34%; P = .02), impaired global longitudinal strain (GLS): –16% ± 1.9% vs –18.3% ± 2.7%; P = .02), and decreased platelet count (226 ± 96 giga per liter [G/L] vs 316 ± 130 G/L) were independently associated with VA. GLS correlated with PVC load every 24 hours (r = 0.39; P < .001) and a cutoff of –17.5% could predict VA with a sensitivity of 82% and a specificity of 63%. VAs are common in patients with SCA, especially in men. This pilot study uncovered GLS as a valuable parameter for improving rhythmic risk stratification.

Dense red blood cells (DRBCs) are associated with chronic clinical manifestations of sickle-cell–disease (SCD). Hydroxyurea (HU) decreases the percent (%) DRBCs, thereby improving its therapeutic benefits, especially the prevention of SCD clinical complications, but parameters influencing %DRBCs remain unknown. The purpose of this study was to determine predictive biological parameters of %DRBC decline under HU. Factors affecting the %DRBC decrease in SCD patients HU-treated for ≥6 months were analyzed. Biological parameters and the %DRBCs were determined before starting HU and after ≥6 months of HU intake. Bivariate analyses evaluated the impact of each biological parameter variation on %DRBC changes under treatment. Multivariate analyses assessed the correlations between the decreased %DRBCs and biological parameters. The %DRBCs declined by 40.95% after ≥6 months on HU. That decrease was associated with less hemolysis, however in several analyses on this group of patients we did not find a statistically significant correlation between decrease in %DRBCs and increase in HbF. Initial %DRBC values were the most relevant parameter to predict %DRBC decline. Our results strengthen the known HU efficacy in SCD management statistically independently of the classical HbF biological response. Decreasing %DRBCs is essential to limiting chronic SCD symptoms related to DRBCs and predictive factors might help prevent those manifestations. The results of this study provide new perspectives on indication for HU use, i.e., to prevent SCD-induced organ damage.