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.
L’hémolyse post-transfusionnelle du patient drépanocytaire est une réaction fréquente chez les patients transfusés ponctuellement, mais sous-estimée du fait de ses caractéristiques immuno-hématologiques et cliniques. L’alloimmunisation anti-érythrocytaire reste la principale cause de cet accident, ceci étant, il existe un certain nombre de cas sans anticorps détectables. La prévention repose donc sur la prévention de l’alloimmunisation, mais tient aussi compte de l’historique transfusionnel des patients, et particulièrement chez les patients transfusés ponctuellement, présentant un risque plus élevé de DHTR. La prévention repose sur l’accès à des CGR phénotypés, mais aussi sur une prévention non spécifique par des traitements immuno-modulateurs, comme le rituximab.
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2.
Transfusion and sickle cell anemia in Africa Diop, S.; Pirenne, F.
Transfusion clinique et biologique : journal de la Société française de transfusion sanguine,
20/May , Volume:
28, Issue:
2
Journal Article
Peer reviewed
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.
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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.
La transfusion reste un traitement majeur de la drépanocytose, à titre préventif mais aussi curatif. Cependant, la réaction transfusionnelle la plus sévère est l’hémolyse post-transfusionnelle retardée qui peut se compliquer d’une hyperhémolyse entraînant dans certains cas une insuffisance multi-organe et le décès du patient. Ce syndrome est souvent sous diagnostiqué du fait de ses caractéristiques particulières au cours de la drépanocytose, essentiellement l’apparition ou la récurrence après une transfusion d’une crise vaso-occlusive, avec une absence d’anticorps anti-érythrocytaires détectables au bilan immun-hématologique. Une retransfusion peut être fatale par exacerbation du processus hémolytique. La prise en charge de cette réaction est basée sur la triade : prévention, diagnostic et traitement. La seule prévention connue est celle de l’allo-immunisation, avec dans certains cas une prévention par le rituximab. Mais cibler uniquement l’allo-immunisation semble insuffisant, puisque de nombreux cas se développent sans anticorps détectables. Le diagnostic est basé sur la formation et l’information de l’ensemble des acteurs médicaux. La reconnaissance de ce syndrome particulier est indispensable. Enfin, le traitement repose sur les thérapeutiques classiques des accidents transfusionnels : immunoglobulines, corticoïdes, mais aussi sur l’érythropoïétine, et plus récemment, l’éculizumab. Des efforts de recherche sont indispensables pour comprendre les mécanismes de cette réaction et adapter, en fonction des mécanismes physiopathologiques prévention et traitement.
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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
To evaluate the effects of a prophylactic transfusion program (TP) on obstetric and perinatal outcomes in pregnant women with sickle cell disease (SCD).
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.
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).
A red blood cell TP may have an independent protective effect on maternal and perinatal adverse outcomes during pregnancy in women with SCD.
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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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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 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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