INTRODUCTION:Cardiac surgery with cardiopulmonary bypass (CPB) induces extreme disturbances in physiological homeostasis, which may trigger vaso‑occlusive crises and hemolysis in patients with sickle cell disease (SCD). The aim was to describe perioperative management, complications and outcomes in SCD patients undergoing cardiac surgery. MATERIAL AND METHODS:Retrospective study including all adult SCD patients who underwent cardiac surgery with CPB from 1996 to 2021 in a French referral center. RESULTS:Twenty‑nine procedures were performed in 21 patients aged 36 [28-43] years. Baseline hemoglobin S (HbS) fraction and hemoglobin levels were 67 [56-83] % and 9 [8-9] g/dL, respectively. After preoperative transfusion management, HbS and hemoglobin were 25 [21-29] % and 10 [10-11] g/dL, respectively. Procedures mainly included valvular repair or replacement (n = 23) or heart transplantation (n = 3). Twenty‑six procedures required intraoperative red blood cell transfusion, with 4 [3-6] units administered. Minimum intraoperative temperature, arterial oxygen partial pressure, and hematocrit were 35.0 [34.4-35.8] °C, 192 [169-207] mmHg, and 19 [18-20.5] %, respectively. Maximum lactate level during CPB was 3.5 [2.9-5.1] mmol/L. Four patients developed infectious complications during the ICU stay; no vaso‑occlusive crisis occurred. ICU length of stay was 5 [3-9] days. Three patients died during the ICU course (two after heart transplantation and one after double valve replacement), all from septic shock. One‑year, five‑year and ten-year survival rates were 85.7%, 64.0% and 54.9%, respectively. DISCUSSION:Despite the acute stress associated with CPB, adult SCD patients experienced acceptable postoperative complications and showed reasonable long‑term outcomes when managed with careful preoperative HbS optimization and a multidisciplinary approach.

BACKGROUND:Sickle cell disease (SCD) affects over 7 million people globally, with blood transfusion remaining a cornerstone of management. However, contemporary transfusion practices across diverse settings remain poorly characterized. We evaluated global transfusion practices for patients with SCD to identify gaps and inform resource prioritization. STUDY DESIGN AND METHODS:We conducted a cross-sectional web-based survey of clinicians and laboratory professionals providing transfusion support for SCD, distributed via email using three professional society's membership lists (July-September 2025). Variables included facility characteristics, pre-transfusion testing capabilities, antigen-matching strategies, transfusion modalities, and barriers to care, stratified by World Bank income classification. RESULTS:After excluding incomplete/duplicate responses, 102 facilities from 39 countries were analyzed; 95 actively treated patients with SCD. Facilities were predominantly public (73%), with 46% in lower-middle-income countries (LMICs). Routine newborn screening was performed by 33% overall (48% high-income countries [HICs] vs. 0% low-income). While ABO/RhD typing was nearly universal, antibody screening was available in only 72% of facilities (0% low-income, 47% LMICs, 98% HICs). Prophylactic RBC antigen matching was performed by 46% (18% LMICs vs. 70% HICs), primarily limited to Rh(CcEe) and K. Automated RBC exchange was available in 44% overall (0% low-income, 25% LMICs, 73% HICs); among facilities with exchange capability, 83% of HICs versus 36% of LMICs could provide exchange within 24 h for acute indications. DISCUSSION:Pronounced income-related disparities exist in SCD transfusion support. Facilities in lower-income settings disproportionately lack antibody testing, prophylactic matching, and timely automated exchange. Targeted infrastructure investment and context-appropriate guidelines are essential for equitable care.

Management of cerebral vasculopathy in sickle cell anemia (SCA) includes standard-care, that is, chronic transfusion (CT) or hydroxyurea, and hematopoietic cell transplantation (HCT). DREPAGREFFE-1 (December 2010/June 2013), a French multicenter trial, was the first prospective trial comparing standard-care to match sibling donor (MSD)-HCT in 67 (35F/32M) SCA children (5-15 year) on CT for abnormal time-averaged mean maximum velocities (TAMMV ≥ 200 cm/s). Seven had a stroke history. We reported that MSD-HCT reduced the highest TAMMVs at 1- and 3-year (p < 0.001) and improved quality of life (QoL) for physical and school functioning. In stroke-free patients, the 3-year stenosis score was lower (p = 0.010). Nevertheless, no significant difference was observed for silent cerebral infarcts (SCI) and cognitive performance. This prompted us to initiate DREPAGREFFE-2 to reevaluate the outcomes at 10 years (September 2022/August 2024) with the same 67 SCA children. No death or stroke occurred in either arm. No rejection or chronic-GvHD arose in the MSD-HCT group (n = 32). In the standard-care group (n = 35), 16 were on hydroxyurea, and 16 on CT at Year 10, and 3 received haploidentical-HCT. After MSD-HCT, the QoL was better, even for social functioning, and the number of hospitalizations, hospitalized days (p < 0.001), and crises (p = 0.001) was lower than on standard-care. In stroke-free patients, stenosis (p = 0.027) and SCI scores (p = 0.041) decreased significantly more after MSD-HCT than on standard-care; working memory (p = 0.016) and processing speed (p = 0.011) improved significantly after MSD-HCT, but worsened on standard-care. These effects were not previously detected with shorter follow-up. This supports earlier consideration of HCT for SCA children with MSD to preserve neurologic function and QoL for a more productive future.

Anemia results from imbalanced hemoglobin or red blood cell production and clearance. Hemolytic anemia, caused by premature red blood cell removal, can be intravascular (in blood) or extravascular (erythrophagocytosis). Hemolysis is common in Sickle Cell Disease (SCD) and Beta-Thalassemia anemia (β-thalassemia), the most prevalent inherited hemolytic anemias. Hemolysis severity is primarily assessed by measuring indirect serum biomarkers such as lactate dehydrogenase, released by cytolysis, bilirubin and haptoglobin. However, these markers do not directly indicate either the cause or the primary site of hemolysis. We introduced a novel plasma heme assay that quantifies all heme-related species in plasma, including hemoglobin, methemoglobin, heme, and hemopexin. Our findings revealed a more profound intravascular red blood cell destruction in SCD compared to β-thalassemia as demonstrated by higher values of plasma hemoglobin, respectively 6.20 and 2.52 μM (p < 0.001), with significant inter-individual variability. In contrast, β-thalassemia patients exhibited higher plasma heme values (11.00 μM vs. 1.51 μM; p < 0.0001) reflecting a probable mixed origin (dyserythropoiesis and hemolysis). Plasma hemopexin was negatively correlated with plasma heme in all patients. Plasma heme exceeded hemopexin scavenging capability in 72% of β-thalassemia and 36% of SCD patients. In β-thalassemia, plasma heme levels were significantly higher in transfusion-dependent compared to non-transfusion-dependent patients, indicating that excess heme reflects clinical severity. In SCD, elevated concentration of excess heme was associated with a significant increased risk of mortality compared to LDH or reticulocytes%. This novel spectral assay offered significant benefits for diagnosis, treatment, and patient management.

BACKGROUND:Filtration failures in sickle cell trait (SCT, AS) blood donations limit the availability of antigen-matched red blood cell concentrates (RBCCs) for transfusion. Carbon monoxide (CO), by stabilizing hemoglobin in its high-affinity relaxed state, may prevent filter clogging and restore leukofiltration efficiency. However, the storage quality and stability of CO-treated RBCCs remain to be evaluated. STUDY DESIGN AND METHODS:RBCCs from normal (AA) donors and AS donors with prior leukofiltration failure were categorized as AA-NC (untreated AA), AA-CO (CO-treated AA), and AS-CO (CO-treated AS). CO treatment consisted of exposing RBCCs to CO gas under controlled conditions before leukofiltration. Filtration success, hematological parameters, metabolic stability, oxidative stress markers, and hemolysis parameters were analyzed on days 0, 14, 28, and 42. RESULTS:CO treatment reversed filter clogging in AS RBCCs, enabling successful leukofiltration without significant hemolysis. It induced approximately 90% COHb, with a slight increase in MetHb due to the injection technique, which remained stable throughout the 42-day storage period. Hematological and metabolic parameters were preserved across groups. CO also reduced free Hb oxidation in both AA and AS RBCCs and limited storage lesions in AA RBCCs, whereas AS RBCs remained more prone to senescence at the end of storage. DISCUSSION:CO treatment enables successful leukofiltration of previously non-filterable AS RBCCs and helps preserve RBC quality during storage. This strategy could enhance the availability of antigen-matched RBCCs and improve transfusion safety in sickle cell disease.

BACKGROUND AND OBJECTIVES:Patient blood management (PBM) is a multidisciplinary approach aimed at reducing the use of blood products. It considers the patient's own blood as a valuable resource to preserve and seeks to avoid the routine use of transfusions to treat anaemia. PBM is primarily based on interventions implemented by anaesthesiologists, including preoperative anaemia correction, targeted administration of coagulation factors and tranexamic acid and strict adherence to transfusion protocols. However, the role of surgical approaches in this context deserves attention. Indeed, surgical innovations over the past two decades have significantly contributed to reducing transfusion requirements. This review will focus on this aspect of PBM. MATERIALS AND METHODS:For this review, we performed a comprehensive search of the PubMed database related to PBM in surgery and also consulted other relevant databases. RESULTS:In the preoperative period, advances in diagnostic techniques, surgical indications and surgical access allow for two blood-sparing options: active surveillance or alternatives to surgery. In the intraoperative period, the development of minimally invasive approaches, the use of innovative haemostatic techniques, per surgery autologous transfusion (cell salvage) and the prevention of hypothermia contribute to the reduction of blood loss and, consequently, the need for transfusion. In the postoperative period, proactive patient management through careful monitoring and the application of enhanced recovery after surgery principles plays a major role in decreasing overall postoperative morbidity. CONCLUSION:These innovations have significantly reduced the need for transfusion in surgical practice. They enhance patient safety by minimizing bleeding and transfusion-related risks.

IntroductionThe treatment of chronic viral infections can often bring viral replication under control. However, chronic immune activation persists and can lead to the development of comorbid conditions, such as cardiovascular disease and cancer. This is particularly true for people living with HIV (PLWH), who have significantly more extracellular vesicles from membrane budding, also called plasma microparticles (MPs), than healthy individuals (HDs), and a much more immunomodulatory phenotype. We hypothesized that the number and phenotypic heterogeneity of MPs can trigger a functional remodeling of immune responses in PLWH, preventing full immune restoration.MethodsWe investigated the rapid impact of three types of MPs — derived from membrane budding in platelets (CD41a+ PMPs), monocytes (CD14+ MMPs) and lymphocytes (CD3+ LMPs) in the plasma of PLWH or HDs—on four cell types (CD4+ and CD8+T lymphocytes, monocytes and DCs).ResultsThese investigations of the short multiple interactions and functions of MPs with these cells revealed an increase in the secretion of cytokines such as IFNg, IL2, IL6, IL12, IL17 and TNFa by the immune cells studied following interactions with MPs. We show that this functional remodeling of immune cells depends not only on the number, but also on the phenotype of MPs.ConclusionThese data suggest that the large numbers of MPs and their impact on functional remodeling in PLWH may be incompatible with the effective control of chronic infections, potentially leading to chronic immune activation and the onset of comorbid diseases.

Background: Red blood cell (RBC) transfusions play a critical role in managing severe acute complications in patients with sickle cell disease (SCD). Evidence from high-income countries (HICs) has also demonstrated the effectiveness of regular transfusions, particularly in preventing stroke in children. However, implementing such protocols in resource-limited countries, such as those in sub-Saharan Africa (SSA), remains challenging due to limited access to blood products and different safety standards. Moreover, data on transfusion practices in these regions are scarce. Objective: To assess the availability of blood products, immunohematological testing, and transfusion practices in French-speaking SSA. Methods: An online survey was conducted by the non-governmental organization (NGO) DrepAfrique between April 12, 2025, and May 8, 2025. A standardized computerized questionnaire, developed by members of the NGO's scientific council, was emailed to 1,960 SSA physicians involved in the care of patients with SCD. Results: A total of 144 practitioners from 16 French-speaking SSA countries participated in the survey. The Democratic Republic of Congo was the most represented country, accounting for 40 respondents (27.8%). Most respondents worked in non-university settings (83/144, 57.6%); 79 (55%) practiced in a SCD referral center. The cumulative number of homozygous SS patients followed in these centers was estimated at approximately 86,000. Each respondent reported having seen a median of 10 [IQR 5; 23] SS patients in the preceding 15 days and having performed a transfusion for 2 [1; 5] of them. Only 38/144 practitioners (26.4%) reported performing phlebotomy prior to transfusion in SS patients with hemoglobin (Hb) >9 g/dL, and 13/144 (9%) had access to erythrocytapheresis. Regarding transfusion indications (suggested from a predefined list), most respondents used transfusions during a vaso-occlusive crisis (VOC) with acute malaria and Hb <6 g/dL (93/144, 64.6%); in cases of anemia with Hb <5 g/dL for 90 of them (62.5%); and when a drop of more than 2 g/dL from baseline Hb occurred for 71 (49.3%). Surprisingly, the use of transfusion was less frequently reported in case of stroke (58/144, 40.3%) or severe acute chest syndrome (53/144, 36.8%). In response to a clinical scenario describing a 7-year-old child with SCD and Hb of 9.4 g/dL (baseline level) presenting with acute hemiplegia and normal brain CT-scan (suggestive of ischemic stroke) in the absence of malaria, only 93/144 respondents (64.6%) indicated that they would perform an immediate transfusion (83 of them (89.2%) with prior phlebotomy). For long-term management of this stroke, 58/144 (40.3%) would initiate a combined treatment of hydroxyurea (HU) and chronic transfusions within the following 6 months, while 51/144 (35.4%) would recommend HU alone. Regarding red cell product type, 138 (95.8%) practitioners reported performing phenotyping of transfused bags, limited to the ABO-RhD systems for 86 (62.3%) of them, and ABO alone for 18 (13%). Only 34/144 (23.6%) practitioners reported screening patients for RBC antibodies before transfusion. The most commonly used blood products (reported as being used “often” or “always”) included whole blood (54/144, 37.6%), ABO-RhD phenotyped packed red blood cells (PRBCs) (73/144, 50.7%), and more rarely ABO-RhDCE-Kell phenotyped PRBCs (23/144, 16%). The limited use of high-quality RBC products or immunohematological testing was primarily due to cost constraints and/or limited availability. Conclusion: This study provides valuable data from one of the largest surveys on transfusion practices for SCD in 16 French-speaking SSA countries. Key challenges include the absence of systematic RBC antibodies screening, the use of RBC products with limited phenotyping, a frequent reliance on whole blood, and difficulties in performing pre-transfusion phlebotomy. These findings call for caution when extrapolating to SSA countries chronic transfusion programs developed in HICs, which are based on significantly higher standards of transfusion safety. This study highlights the urgent need for context-appropriate training programs to optimize transfusion practices and decision-making processes in SSA, particularly in the acute management of stroke. In light of these constraints, a wider use of HU should be strongly encouraged.

Forty-two questions were evaluated concerning management of emergencies and critical illnesses in paediatric and adult patients with sickle cell disease. The assessment covered the following areas: patient referral, vaso-occlusive crisis, acute chest syndrome, transfusion therapy, and priapism. The patient referral category included guidelines for admission to intensive care unit and management at specialized reference centers. The vaso-occlusive crisis topic encompassed pain management, hydration, incentive spirometry, and target oxygen saturation levels. For acute chest syndrome, the focus areas included imaging techniques such as lung ultrasound, computed tomography scans, and echocardiography; treatment with systemic corticosteroids; non-invasive ventilation; prophylactic and therapeutic anticoagulation; and procalcitonin and antibiotic therapy. The section on transfusion therapy addressed indications and methods of transfusion, as well as the diagnosis and prediction of delayed hemolytic transfusion reactions. A total of 45 recommendations were proposed, including 14 specific to adults, 13 specific to pediatrics, and 18 applicable to both adults and children, along with three therapeutic algorithms. The Grade of Recommendation Assessment, Development, and Evaluation (GRADE) methodology was adhered to throughout the process. Sixteen recommendations were based on a low level of evidence (GRADE 2+ or 2−), while 26 were based on evidence that could not be classified under the GRADE system and were therefore considered expert opinions. Finally, for three aspects of sickle cell disease management, the experts concluded that no reliable recommendations could be made based on the current state of knowledge. The recommendations and therapeutic algorithms received strong agreement from the experts.

Globally, sickle cell disease (SCD) is the most common inherited haemoglobinopathy. The highest burden of SCD is encountered in low- and middle-income countries (LMICs), most of which lack the resources to contend with the disease. There is a marked divide between care for individuals with SCD in high-income countries (HICs) versus LMICs, whereby the few disease-modifying therapies and curative regimens are only accessible to those in HICs. As such, blood transfusion remains central to the emergent treatment and prevention of complications of SCD. However, there are a myriad of related challenges in LMICs, which have impeded efforts to treat patients with SCD effectively. In addition to blood safety and availability, examples that impact SCD specifically include capabilities to detect and/or manage red blood cell alloimmunization, capacity for automated red cell exchange, limited immunohematology, suboptimal quality oversight with a lack of safeguards to prevent transfusion of incompatible blood and limited or absent post-transfusion surveillance to detect and/or manage transfusion-associated adverse events. Consequently, clinical practices that are otherwise regarded as standard of care in HICs remain the exception in LMICs, highlighting disparities in care. A multifaceted approach that prioritizes transfusion support in LMICs is needed to improve care for patients with SCD.

IntroductionThe immunological profiles of CD4+ T lymphocytes (TLs) from patients with hematological malignancies differ between patients who have and have not received transfusions. There may be several reasons for these differences, including the presence of extracellular vesicles (EVs) derived from plasma membrane budding and present in the platelet concentrates. Indeed, EVs can modulate the immune system through interactions with many immune cells, but the underlying mechanisms remain incompletely understood.MethodsWe therefore investigated how interactions with CD41a+ EVs cause immune cells to change phenotype and function. CD41a+ EVs were cultured with TLs, B lymphocytes, and monocytes. Given the potential involvement of monocytes in leukemia progression, we performed a new original multi-omics study to confirm the protein changes and gene activation observed following interaction with CD41a+ EVsResultsThe CD41a+ EVs had immunomodulatory effects on all these cell types but this effect depended on the numbers of EVs. CD4+ TLs required large numbers of CD41a+ EVs for activation, whereas monocytes were the most sensitive. With the new multi-omics technique, we confirmed the direct effects of CD41a+ EVs on protein phenotype and gene activation.ConclusionTransfusion EVs should be considered during the immunological follow-up of patients after transfusion to detect immunological effects on malignant hemopathies, and during the development of new immunotherapies.

Introduction: Hemolysis is defined as an imbalance between the rate of red blood cell (RBC) production and destruction, leading to reduced lifespan of RBCs, as they are removed from the circulation. Measuring RBC lifespan is of interest to better evaluate hemolytic anemia severity. To date, the methods used to assess RBC lifespan are invasive and time-consuming, requiring infusion of autologous labeled RBCs and longitudinal follow-up. Normal RBC aging is characterized by physiological alterations such as cellular dehydration and decrease in enzymes activity. Simultaneously, the concentration of glycated Hb (G-Hb), of which HbA1c form is the most prevalent, increases. Hb glycation is a non-enzymatic reaction whose intensity is modulated by plasma glucose concentration and RBCs longevity. Consequently, in non-diabetic subjects, the level of Hb glycation is directly proportional to RBCs lifespan in a linear-dependent relationship. Moreover, in certain diseases such as sickle cell disease (SCD) or X-linked G6PD deficiency, there can be heterogeneous lifespan that require a cellular approach rather than an average measure. To circumvent the disadvantages of the currently used methods, we developed a novel assay to measure RBC lifespan based on the assessment of intracellular glycated Hb by flow cytometry. This method is based on technology we have developed to measure fetal and sickle hemoglobins per RBC (Hebert, 2020). Methods: G-Hb was measured in RBCs from healthy donors (HD) and non-transfused SCD patients, in reticulocytes (RNA-positive cells) and RBCs. Exclusion criteria were diabete or pre-diabete. HD samples were splited into two sub-groups. Group-A (n=50) was used to determine the lifespan of reticulocytes based on the disappearance of RNA staining (time required for a reticulocyte to mature to an erythrocyte). Group-B (n=46) was used to assess accuracy of the measure of the half-life.Single cell G-Hb was assessed by flow cytometry using a fluorescent monoclonal anti-human HbA1c antibody. Glycation of Hb in reticulocytes was assessed by the addition of thiazole orange to stain the RNA. A standard linear equation was calculated as the relationship between thiazole orange and glycated Hb intensity and was used to convert the G-Hb fluorescence into time. Results: In HD RBCs, glycated Hb fluorescence intensity followed a log-normal distribution in every samples (n=96), indicating homogeneity of the RBC population in aging. G-Hb mean fluorescence intensity (MFI) of every RBC was set as the level of glycation obtained for normal half-life of RBCs (50 days). In HD reticulocytes, G-Hb intensity was negatively correlated to RNA intensity in a Log-linear dependent manner (p<0.001). This relationship was obtained in all HD indicating its consistency. A standard linear curve was calculated as the relationship between decrease in RNA and increase in G-Hb intensity, using mean values measured in HD. A delta-RNA intensity was calculated as the difference in thiazole orange intensity between the highest and the lowest value. The corresponding delta-glycated Hb intensity is the increase in glycation during the time reticulocytes mature into erythrocytes. Using the standard equation, and by setting glycated Hb MFI equals 50 days, reticulocytes lifespan (time to lose RNA) was 3.6±0.8 days in group-A. The G-Hb MFI measured in RBCs form HD in group B was converted into time using the standard equation, by setting the time reticulocytes mature into erythrocyte as 3.6±0.8 days. RBCs half-life was 49.5±11.5 days. In SCD RBCs, GHb intensity was not following a log-normal distribution, indicating intra-individual variability in aging. Using the previously calculated standard equation in HD, the SCD reticulocytes lifespan was 3.3±0.3 days and the mean RBC lifespan was 77±8.5 days (n=16). Conclusion: Single-cell glycated Hb, as assessed by flow cytometry, enables the precise measurement of RBC lifespan. Normal RBCs half-life we measured using this method aligns with findings from all other studies using reference methods (51 Cr- or biotin-labeled RBCs). The capacity to simultaneously measure the age of different RBC subpopulations makes this method highly valuable in all hemolytic conditions. This novel tool is non-invasive, requires only a single-point measurement, and is easy to implement. It should be considered for evaluating the efficacy of treatments aimed at improving hemolysis, such as pyruvate kinase activators or allosteric Hb modulators.

Background Transfusion (TF), or exchange transfusion (ExTF), is a major therapy for sickle cell disease (SCD) patients. However, these transfusions can lead to complications, including Delayed Hemolytic Transfusion Reaction (DHTR), which occurs in 4–11% of cases and leads to the hemolysis and rapid disappearance of transfused red blood cells. Since SCD patients are unable to produce HbA, post-transfusion HbA levels can be used to assess the efficacy of TF. Monitoring the disappearance of HbA mass after RBCs transfusion by means of the “DHTR nomogram” is currently used for the diagnosis of DHTR in our reference center. However, this method is not widely used due to a lack of post-transfusion biological tests, particularly for HbA. Clinicians usually check routinely post-transfusion Hemoglobin (Hb), but not the % of HbA . The aim of this study was to better determine the immediate post TF percentage of HbA per unit of transfused Red Blood Cells(RBCs) in SCD adult patients. Methods In this single center retrospective study, biological data from SCD adult patients who had undergone ExTF or TF, either at the initiation of their TF program or during an acute complication were collected. Eligible patients were adults SCD patient with no recent (<3 month) TF confirmed by the French blood bank center with available Hb electrophoresis. According to French SCD guidelines, all patients received two units of RBCs, with or without prior phlebotomy. HbA levels (as measured by high-performance liquid chromatography with cation exchange) were measured within 48 hours of the procedure. All participants provided informed consent to participate in the study. Results We retrospectively collected data from 84 cases of ExTF or TF performed in our hospital. Among these, 81 patients had homozygous sickle cell disease (SS) and 3 had Sβ⁰-thalassemia. The cohort included 47 men and 37 women, with a median age of 37 years [IQR: 27–41] and a median weight of 68 kg [IQR: 60–78] at time of ExTF or TF. ExTF or TF was performed during acute complication in 36 patients and at the initiation of a TF program in 48 patients. The median pre-transfusion Hb level was 7.9 g/dL [IQR: 6.8–9.1], increasing to 9.4 g/dL [IQR: 8.4–10.3] after the TF / ExTF . The level of HbA rose from 0% (pre TF/ETF) to 22.7% [IQR: 20.0–24.8] after two RBC units. To evaluate the impact of pre-transfusion hemoglobin levels on TF efficiency, patients were stratified into four groups: Hb < 7 g/dL, 7–8.4 g/dL, 8.5–9.5 g/dL, and > 9.6 g/dL. Following the recommended bleeding volumes provided by our center. The HbA gain per RBC unit was as follows: • 12.3% [IQR: 11.2–13.8] for the group with Hb < 7 g/dl, and a post TF at 8,1[7,7-8,4]g/dl • 11.2% [IQR: 10.1–12.3] for the group with Hb 7–8.4 g/dl and a post TF at 9,2[8,7-9,8]g/dl • 11.3% [IQR: 10.2–11.9] for the group with Hb 8.5–9.5 g/dl and a post TF at 10,3[9,6-10,5]g/dl • 10.3% [IQR: 9.4–12.3] for the group with Hb > 9.6 g/dl and a post TF at 10,7[10,4-11,2]g/dl These results show that the HbA level remains relatively stable across different pre-TF Hb levels. And Post TF HB levels are optimized. Conclusion This provides some new evidence showing that estimating the percentage of HbA after TF or ExTF is a reliable and stable marker in SCD adult patients. Based on these results, HbA level after two RBC units ranges from 22% to 24%, suggesting that each unit contributes approximately for 10- 12%. The lower the pre-transfusion Hb level, the higher the resulting HbA percentage. The homogeneity of the results must encourage clinicians to use this parameter and the DHTR nomogram that was previously published (American Journal of Hematology, Vol. 00, No. 00, Month 2016) in order to detect as soon as possible the onset of DHTR. Furthermore, the combination of phlebotomy and the transfusion of two RBC units, as recommended in the French guidelines, appears to optimize Hb level. This strategy helps avoid increasing Hb in patients with higher Hb level and the risk of hyperviscosity , as well as significant Hb rises in patients with lower pretransfusion Hb levels. .