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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Murine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization. In vaccination studies, the intensity of ...antigen-specific responses depends on the delay between antigen and adjuvant administration, with a short delay limiting immune responses. In mouse models of alloimmunization, the delay between the injection of Toll-like receptor agonists and transfusion is usually short. In this study, we hypothesized that the timing of Toll-like receptor 3 agonist administration affects red blood cell alloimmunization. Poly(I:C), a Toll-like receptor 3 agonist, was administered to B10BR mice at various time points before the transfusion of HEL-expressing red blood cells. For each time point, we measured the activation of splenic HEL-presenting dendritic cells, HEL-specific CD4(+) T cells and anti-HEL antibodies in serum. The phenotype of activated immune cells depended on the delay between transfusion and Toll-like receptor-dependent inflammation. The production of anti-HEL antibodies was highest when transfusion occurred 7 days after agonist injection. The proportion of HEL-presenting CD8α(+) dendritic cells producing interleukin-12 was highest in mice injected with poly(I:C) 3 days before transfusion. Although the number of early-induced HEL-specific CD4(+) T cells was similar between groups, a high proportion of these cells expressed CD134, CD40 and CD44 in mice injected with poly(I:C) 7 days before transfusion. This study clearly shows that the delay between transfusion and Toll-like receptor-induced inflammation influences the immune response to transfused red blood cells.
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.
La transfusion reste un des traitements majeurs de la drépanocytose. L’allo-immunisation antiérythrocytaire est fréquente du fait du polymorphisme des antigènes de groupes sanguins entre les patients d’origine Africaine et Antillaise et les donneurs essentiellement d’origine Européenne en France métropolitaine. L’allo-immunisation est associée au risque d’hémolyse post-transfusionnelle avec mise en jeu du pronostic vital. Au-delà des antigènes communs, un certain nombre de variants du système RH peuvent être impliqués dans ces accidents, d’autant que ces variants sont fréquents dans la population afro-antillaise. Si certains variants sont clairement associés à un risque d’allo-immunisation et d’hémolyse chez les patients, tel le phénotype RH : −18, pour la grande majorité, les données sont peu claires. La connaissance de l’impact clinique des variants RH chez les drépanocytaires est d’un intérêt majeur. De nombreux outils moléculaires sont développés pour caractériser ces variants, mais ils ne permettent pas de distinguer ceux réellement d’intérêt pour les patients, et qui donc nécessitent une prévention de l’allo-immunisation. Dans cette revue, nous faisons état de l’ensemble des données de la littérature sur ce sujet, ainsi que de notre expérience au cours de la transfusion des patients drépanocytaires.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
La transfusion est un des traitements majeurs de la drépanocytose. Les réactions d’hémolyse post-transfusionnelles retardées ne sont pas rares chez les patients drépanocytaires, et peuvent mettre en jeu le pronostic vital. La principale cause est la production par ces patients d’alloanticorps antiérythrocytaires. La fréquence élevée d’alloimmunisation est surtout due au polymorphisme des antigènes de groupes sanguins entre donneurs d’origine caucasienne et patients d’origine afro-antillaise. Sur un plan immuno-hématologique, ces accidents présentent des caractéristiques au cours de cette maladie : les alloanticorps classiques, aux propriétés hémolytiques bien connues sont les plus souvent rencontrés, mais des anticorps non classiquement significatifs, des auto-anticorps, des anticorps liés à un antigène « partiel » du patient ou à la présence d’un sang rare peuvent aussi être retrouvés au cours de ces accidents. Dans un tiers des cas, aucun anticorps n’est retrouvé. L’alloimmunisation restant la cause majeure de ces accidents, il est primordial de promouvoir le don de sang dans les populations d’origine afro-antillaise.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
La transfusion reste le traitement majeur de la drépanocytose. Les besoins transfusionnels sont croissants. Les patients, essentiellement d’origine africaine ou Antillaise, présentent des ...caractéristiques immuno-hématologiques particulières, dont il est indispensable de tenir compte. Ces caractéristiques sont à l’origine d’une ressource faible en concentrés de globules rouges phénocompatibles et d’accidents d’hémolyses post-transfusionnelles plus fréquents que dans la population générale. L’optimisation de la sécurité immunologique des transfusions concerne toutes les étapes de la chaîne transfusionnelle. Cet article a pour objectif de tracer un état des lieux en France métropolitaine et de déterminer les axes de réflexion et d’optimisation, au niveau de la collecte, de la promotion du don, de la préparation où se pose notamment le problème du trait drépanocytaire, de la qualification biologique des dons d’intérêt, mais aussi des modes d’approvisionnement des établissements de transfusion sanguine concernés par la transfusion de ces patients, des protocoles transfusionnels et analyses pré-transfusionnelles. La recherche et la formation ont aussi un rôle majeur à jouer.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
1 Etablissement Français du Sang, Ile de France, Hôpital Henri Mondor, Créteil;
2 Centre de Référence des Cytopénies Auto-Immunes, Hôpital Henri Mondor, Créteil;
3 Service des Maladies Génétiques du ...Globule Rouge, Hôpital Henri Mondor Créteil;
4 Service de Médecine Interne, Hôpital Henri Mondor, Créteil;
5 Laboratoire dImmunologie, Hôpital Henri Mondor, Créteil;
6 Université de Poitiers, EA 3806, CHU de Poitiers
Correspondence: France Noizat-Pirenne, MD, PhD, Etablissement Français du Sang dIle de France, 51 Avenue du Maréchal de Lattre de Tassigny, 94000, Créteil, France. Tel: 331 56 72 76 37; Fax: 331 56 72 76 01, E-mail: france.noizat-pirenne{at}efs.sante.fr
Delayed hemolytic transfusion reaction (DHTR), a life-threatening transfusion complication in sickle cell disease (SCD), is characterized by a marked hemoglobin drop with destruction of both transfused and autologous red blood cells (RBCs) and exacerbation of SCD symptoms. One mechanism of RBCs destruction is auto-antibody production secondary to transfusion. As rituximab specifically targets circulating B cells, we thought that it could be beneficial in preventing this immune-mediated transfusion complication. We report the case of a SCD patient who previously experienced DHTR with auto-antibodies and who needed a new transfusion. DHTR recurrence was successfully prevented by rituximab administration prior transfusion, supporting the safe use of rituximab to prevent DHTR in SCD patients as a second line approach when other measures failed.
Key words: Sickle cell disease, rituximab, transfusion, auto-antibodies.
Les analyses de biologie moléculaire sont devenues d’un accès plus répandu ces cinq dernières années, grâce aux développements des techniques, à la possibilité d’utiliser des kits commerciaux. Il ...n’en reste pas moins que ces analyses restent encore coûteuses, en réactifs, et matériels, et nécessitent des laboratoires dédiés. Sur le plan national, mais aussi international, la sérologie reste la technique de référence pour la plus grande partie des analyses immuno-hématologiques. À ce jour, les analyses moléculaires restent des analyses complémentaires pour résoudre un certain nombre de situations où la sérologie trouve ses limites. Dans cette revue, nous détaillerons les indications principales des analyses en biologie moléculaire, chez les donneurs et les receveurs, en tenant compte des moyens techniques à notre disposition et des connaissances actuelles sur le polymorphisme des groupes sanguins, sachant que le principal paramètre devant dicter la prescription d’une analyse moléculaire est un bénéfice en termes de sécurité transfusionnelle et/ou obstétricale.
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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