Les anémies aiguës et la stratégie transfusionnelle chez les drépanocytaires adultes: Acute anemias transfusion strategy in adult sickle cell patients.

Worsening of anemia is very common in sickle cell disease. It is important to investigate specific complications related to sickle cell disease but also other causes of anemia in general. Transfusions or exchange transfusions are major therapeutic options and are frequently used for acute complications of sickle cell disease but also for primary and secondary prevention of some of the chronic complications. The transfusion strategy has been modified since the awareness of post-transfusion hemolysis by taking into account the transfusion risk score. A strong collaboration between the patient's expert center, the Blood center and the patient's hospitalization unit is required to make decisions. © 2023 Société nationale française de médecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

Evaluation of a prophylactic transfusion program on obstetric outcomes in pregnant women with sickle cell disease: A single centre retrospective cohort study.

OBJECTIVE: To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD). METHODS: This retrospective cohort study included all singleton pregnancies among women with SCD in a French university tertiary care center between 1 January 2004 and 31 December 2017. The TP group included patients selected according to the French guidelines who received regular red blood cell transfusions during pregnancy until delivery. The factors associated with TP indication [year of birth, SCD genotype, history of acute chest syndrome and delayed hemolysis transfusion reaction (DHTR) risk score] were taken into account in a propensity score. A composite obstetric adverse outcome was defined associating birth before 34 gestational weeks and/or pre-eclampsia and/or small for gestational age and/or abruption and/or stillbirth and/or maternal death and/or neonatal death. RESULTS: In total, 246 pregnancies in 173 patients were analyzed. Twenty-two pregnancies with a history of DHTR were excluded. A higher frequency of TP was found before 2013 [119/148 (80.4%) vs 38/76 (50%); p < 0.001]. Rates of preterm birth before 34 gestational weeks (5.6% vs 19.7%; p = 0.001), vaso-occlusive crisis (36.5% vs. 61.8%; p < 0.001), and acute chest syndrome (6.1% vs. 14.5%; p = 0.04) during pregnancy were decreased significantly in the TP group. Among the groups with and without composite obstetric adverse outcomes, the frequency of TP was 52.6% and 74.7%, respectively [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.09-1.02]. The multivariate analysis shows that the TP was associated with a significant reduction in the risk of composite obstetric adverse outcomes (OR 0.28, 95% CI 0.08-0.97; p = 0.04). CONCLUSION: A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.

Transfusion and sickle cell anemia in Africa.

Sickle cell anemia (SCA) is the commonest life-threatening genetic disorder in tropical regions, particularly in sub-Saharan Africa. It has been estimated that between 50-90% of SCA children will die in Africa before the age of 5, corresponding to a number of 150,000-300,000 annual SCA child deaths, which represents 5-10% of total child mortality. Transfusion support remains an essential component in the management of patients with SCA and has made a significant contribution to improving patient morbidity and mortality. In Africa where the majority of patients with SCA reside, many blood transfusion challenges remains, including shortage of blood supplies, risks related to infectious and immunologic potential side effects and limitation on the diagnosis and management of post-transfusion iron overload. The proportion of transfused SCA patients varies from different studies, between 30% and 90%. This variation can be related to environmental factors, disease genetic factors and other factors including the low availability of blood, difficulties in accessing to health care and inadequacies of the transfusion system. Because blood transfusion therapy is an integral component of the management of SCA, improved efforts and strategies to overcome these challenges and optimize blood transfusion practices are needed in African countries.

Prevention of delayed hemolytic transfusion reaction.

Post-transfusion hemolysis is the most frequent immune reaction to transfusion in sickle cell disease. Its frequency is underestimated due to its biological and clinical characteristics. It results principally from the high incidence of alloimmunization in these patients, but no antibodies are detectable in 30% of cases. Prevention is based on the prevention of alloimmunization through the use of matched RBCs for highly immunogenic blood groups, taking into account the patient's transfusion history, particularly in patients undergoing occasional transfusion, which is associated with a higher risk of DHTR development than chronic transfusion. In addition to the use of matched RBCs, the prevention of alloimmunization through immunotherapy should be considered.

Management of the blood supply for a Jk(a-b-) patient with an anti-Jk3 in preparation for an urgent heart transplant: An illustrative example of a successful international cooperation.

The Kidd blood group system currently comprises two polymorphic and antithetical antigens, Jka and Jkb, and one high-prevalence antigen, Jk3. Jknull individuals do not express any of the Kidd antigens, and are at risk of developing an anti-Jk3 which is known to be dangerous and responsible for acute or delayed hemolytic transfusion reaction. We report a case of an immunized Jknull patient, who was scheduled to undergo a heart transplant. In order to organize his blood provision management, two conference calls were held between the clinical team and the different staff involved in this challenging blood supply. In light of the blood needs, the available resources, and the constraints, a mix of fresh and frozen units were used. As the supply from France was not sufficient, Finland and New Zealand provided the majority of the fresh units. We report here how this international supply chain was organized, including the difficulties that we encountered. Anticipation, communication and flexibility were essential in making this heart transplant possible without needing to transfuse incompatible units.

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention, diagnosis, treatment.

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.

Transcriptomic Signature of the CD24hi CD38hi Transitional B Cells Associated With an Immunoregulatory Phenotype in Renal Transplant Recipients.

The role of B cells after transplant regarding allograft rejection or tolerance has become a topic of major interest. Recently, in renal transplant recipients, a B cell signature characterized by the overexpression of CD19+ CD38hi CD24hi transitional B cells has been observed in operationally tolerant patients and in belatacept-treated patients with significantly lower incidence of donor-specific antibodies. The phenotypic and functional characterization of these transitional B cells is far from exhaustive. We present the first transcriptomic and phenotypic analysis associated with this cell phenotype. Three populations were studied and compared: (i) transitional CD24hi CD38hi , (ii) CD24+ CD38- , and (iii) CD24int CD38int B cells. Transcriptome bioinformatic analysis revealed a particular signature for the CD24hi CD38hi population. Phenotypic analysis showed that CD24hi CD38hi transitional B cells also expressed CD9, CD10, CD1b and inducible T cell costimulator ligand (ICOS-L) markers. In addition, we found enrichment of IL-10+ cells among CD24hi CD38hi cells expressing ICOS-L and CD1b, the latter showing regulatory properties. Renal transplant recipients treated with belatacept exhibited significant expression of CD1b. Our results show that transitional CD24hi CD38hi B cells exhibit a distinct and specific profile, and this could be helpful for understanding of immune-regulatory mechanisms and immune monitoring in the field of organ transplant and autoimmune disease.

Rare and transient anti-D antibody response in D(-) liver transplant recipients transfused with D(+) red blood cells.

A retrospective analysis was conducted on 20 D(-) liver transplant (LT) recipients transfused with D(+) RBCs perioperatively and screened for RBC antibodies between 2 and 6 months later. None developed anti-D detectable by the indirect antiglobulin test. Two patients produced weak anti-D that reacted only with papain-treated RBCs at 10 and 11 days without any sign of immune haemolysis. Antibodies became quickly undetectable. These data suggest an unusual pattern of alloimmunization in LT recipients with rapid, weak and transient antibody response and support the safety of transfusing D(+) RBCs in most of D(-) patients during LT surgery.

The use of rituximab to prevent severe delayed haemolytic transfusion reaction in immunized patients with sickle cell disease.

BACKGROUND: Delayed haemolytic transfusion reaction (DHTR) is mainly caused by an immune response to transfused red blood cells (RBCs). Immunized patients have a high risk of producing antibodies in response to further transfusion. Controlling the immune response to RBCs is therefore a major goal in sickle cell disease (SCD). STUDY DESIGN: We report an observational study of eight alloimmunized SCD patients with history of severe DHTR who were treated with rituximab before a new transfusion to prevent further immunization and DHTR. RESULTS: Five patients showed a good clinical outcome following transfusion preceded by preemptive treatment with rituximab. The remaining patients presented mild DHTR. In all patients, the results of post-transfusion screening tests were identical to those of pretransfusion tests; no newly formed antibodies were detected. CONCLUSION: These cases suggest that rituximab prevents at least occurrence of newly formed antibodies in high responders and minimizes the risk of severe DHTR. This study confirms that DHTR is complex in SCD and does not rely only on the classical antigens/antibodies conflict. Considering potentially serious adverse effect of rituximab, this treatment should be considered cautiously, and only when transfusion is absolutely necessary in patients with history of severe DHTR linked to immunization.

[Transfusion and sickle cell disease: axes of transfusion safety optimization]. / Transfusion et drépanocytose : axes d'optimisation de la sécurité transfusionnelle.

Transfusion remains a major treatment in sickle cell disease. In France, sickle cell disease patients are mainly from Sub-Saharan Africa and West Indies. The immuno-hematological characteristics of these patients of African ancestry induce a short supply of compatible packed red blood cells and an increased rate of haemolytic transfusion reactions, compared to the general transfused population. The optimization of transfusion safety relies on all steps of the transfusion chain. This article aims to describe the current situation in France and to determine the axes of optimization at all steps of the transfusion organization: promotion of donation, preparation of products, taking into account the sickle trait, qualification of packed red blood cells, supply of the blood banks concerned by transfusion of these patients, transfusion protocols and pre transfusion analysis. Research and formation play an important part.

[The actual place of molecular analysis for donors and recipients in red blood cell immuno-hematology]. / Place actuelle de la biologie moléculaire en immuno-hématologie donneur et receveur.

Molecular testing in red blood cell immuno-haematology is used extensively since the last 5 past years because of the technical developments and the possibility to use commercial kits. But these analyses have a high cost and rely on dedicated laboratories. Therefore, serology remains a reference technique for many laboratories in France, and in the world. Molecular analyses are used to resolve problems that cannot be resolved by serology. In this review, we will detail the main indications of molecular analysis, in donors and recipients, taking into account the technical tools that we can use, and the knowledge that we have about blood groups and their different variants. In this context, we have to remember that a molecular analysis has to be performed only if there is a benefice for the patient in the transfusion or the obstetrical setting.

Relevance of alloimmunization in haemolytic transfusion reaction in sickle cell disease.

Transfusion remains a key treatment in sickle cell disease. The occurrence of a delayed haemolytic transfusion reaction is not rare and is a life-threatening event. The main cause of delayed haemolytic transfusion reaction is production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in sickle cell disease patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, delayed haemolytic transfusion reaction in sickle cell disease patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of delayed haemolytic transfusion reaction, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available.

Relevance of RH variants in transfusion of sickle cell patients.

Transfusion remains the main treatment of sickle cell disease patients. Red cell alloimmunization is frequent because of the antigen disparities between patients of African descent and donors of European ancestry. Alloimmunization is associated with severe hemolytic transfusion reaction, autoantibody formation, and difficulties in the management of transfusion compatibility. Beside common antigens, a number of different RH variant antigens found in individuals of African descent can be involved in alloimmunization. If some variants, such as Hr(S) negative antigens, are known to prone significant alloantibodies and delayed hemolytic transfusion reactions, it is not clear whether all the described variants represent a clinical risk for sickle cell disease patients. The knowledge of the clinical relevance of RH variants is a real issue. An abundance of molecular tools are developed to detect variants, but they do not distinguish those likely to prone immunization from those that are unlikely to prone immunization and delayed hemolytic transfusion reactions. A strategy of prevention, which generally requires rare red blood cells, cannot be implemented without this fundamental information. In this review, we discuss the relevance of RH variants in sickle cell disease, based on the published data and on our experience in transfusion of these patients.

[Murine models in blood transfusion: allo-immunization, hemolysis]. / Modèles murins en transfusion sanguine: allo-immunisation, hémolyses.

Mice represent an animal model that can be easily manipulated. Mice have been used to model many human diseases. This review addresses murine models of immunity directed against red blood cell antigens as well as models of antibody and non-antibody mediated hemolysis. These models allow for a better understanding of the side effects of transfusion, such as red blood cell allo-immunization and post-transfusional hemolytic reactions. They also help explore strategies to treat and prevent these side effects in ways that would not be available using clinical research alone.