Br J Haematol

Acquired haemophilia A (AHA) is a rare haemorrhagic disease characterised by new-onset haemorrhagic symptoms associated with a dramatic decrease in factor VIII levels and an anti-factor VIII neutralising autoantibody concentration >0.6 Bethesda units. Elderly people are often affected, whereas children are rarely affected; the paediatric incidence reported in the literature is about 0.045 case/million/year. For some time, the paediatric standard of care has been that for adults, but clinicians have often reported poor outcomes. Here, we describe the largest retrospective paediatric AHA cohort assembled to date, including eight patients diagnosed in France from 2000 to 2020

Pubertal development of transfusion-dependent thalassemia patients in the era of oral chelation with deferasirox: results from the French registry

Not available

Les leucémies aigües lymphoblastiques congénitales (expérience française entre 1990 et 2010)

OBJECTIFS : Les leucémies aigues lymphoblastiques congénitales sont une pathologie rare, peu connue et de pronostic très sombre. L'objectif de ce travail est de rapporter et analyser l'expérience française dans ce domaine entre 1990 et 2010, et de comparer les données obtenues à celles des travaux de référence récemment publiés. A partir de ces éléments, ce travail discute les différentes attitudes thérapeutiques dans le but d'améliorer la prise en charge de ces nourrissons, tant sur le plan thérapeutique que de la qualité de vie. PATIENTS ET METHODES : Etude observationnelle rétrospective multicentrique reprenant tous les cas de leucémie aigue lymphoblastique congénitale diagnostiqués en France métropolitaine de Janvier 1990 à Décembre 2010, et répertoriés dans le Registre National des Hémopathies malignes de l'Enfant (22 enfants inclus). Recueil et analyse statistique des caractéristiques cliniques et biologiques, des modalités de traitement, du devenir des patients et des principaux facteurs pronostiques reconnus. RESULTATS : L'âge médian au diagnostic était de 5,5 jours. Il s'agissait pour la majorité de leucémies proB, CD10-, présentant dans 77 % des cas un remaniement en 11q23. Un traitement curatif d'emblée était instauré dans 62 % des cas, un traitement palliatif dans 24 % des cas et une attitude d'attente dans 14 % des cas. La survie globale à 2 ans était de 4,5 %, la médiane de survie de 5,5 mois. 92 % des enfants en rémission complète ont rechuté. Tous les enfants ayant rechuté sont décédés. CONCLUSION : Les leucémies congénitales restent de pronostic particulièrement péjoratif malgré les modifications apportées aux protocoles et attitudes thérapeutiques ces dernières années. L'instauration d'un traitement curatif modifie peu le taux de la survie mais allonge significativement sa médiane, celle-ci restant quasi exclusivement hospitalière. Un traitement systématique de tous les enfants ne paraît donc ni raisonnable, ni acceptable sur le plan éthique.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Acta Haematol

Immunization against the platelet αIIbβ3 glycoprotein due to blood transfusion represents one of the most severe complications in Glanzmann thrombasthenia (GT) disease. Anti-αIIbβ3 isoantibodies development may lead to ineffective platelet transfusion and can, in case of pregnancy, cross the placenta leading to fetal thrombocytopenia. We describe here the case of a girl with type I GT who developed high rates of anti-αIIbβ3 isoantibodies after first and unique blood transfusion. Surprisingly, this patient had only received red blood cell concentrates and immunization was presumably stimulated by the residual presence of platelets in concentrates. This study emphasizes the need for regular anti-αIIbβ3 antibodies screening in GT, even though patients have never been previously transfused with platelet concentrates

Br J Haematol

International audienc

A new case with Hermansky-Pudlak syndrome type 9, a rare cause of syndromic albinism with severe defect of platelets dense bodies

Hermansky-Pudlak syndrome (HPS) is a rare form of syndromic oculocutaneous albinism caused by disorders in lysosome-related organelles. Ten genes are associated with different forms of HPS. HPS type 9 (HPS-9) is caused by biallelic variants of BLOC1S6. To date, only three patients with HPS-9 have been reported. We described one patient presenting with ocular features of albinism. Genetic analysis revealed two compound heterozygous variants in the BLOC1S6 gene. Extended hematological studies confirmed the platelet storage pool disease with absence of dense granules and abnormal platelet aggregation. By reviewing the previous published cases we confirm the phenotype of HPS-9 patients. This patient is the only one described with dextrocardia and abnormal psychomotor development

Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A

International audienceA round one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more lifethreatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII < 1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P= 0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7-20.6) with Factane, 20.4% (95% CI: 14.0-29.1) with Advate, and 31.6% (95% CI: 23.5-41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide

Homozygosity for the hyperunstable hemoglobin variant Hb Agrinio ( HBA2 :c. 89T >C) leads to severe antenatal anemia: Eight new cases in three families

International audienc

J Thromb Haemost

Essentials The c.1544+1G>A mutation was identified in Gypsy Glanzmann thrombasthenia (GT) patients. Gypsy GT patients express normal α β carrying HPA-1b epitopes. To demonstrate HPA-1a alloimmunization by modified antigen capture assays. Gypsy GT patients could develop anti-HPA-1a alloantibodies against β and α β . ABSTRACT: Background Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by the absence or the dysfunction of the platelet α β integrin. A founder mutation in the ITGA2B gene was previously identified in French Gypsy patients. Interestingly, this mutation was strongly linked to the human platelet antigen-1b (HPA-1b). The HPA-1bb Gypsy patients are at risk of isoimmunization against α β , as this complex is not expressed at their platelet surface. Tentatively, they would, however, not have an increased risk of developing anti-HPA-1a alloantibodies by exposure of α β on platelets from random platelet transfusions. However, the β chain can also associate with the α subunit expressed at the platelet surface. Because Gypsy GT patients express normal α β carrying HPA-1b epitopes, these patients might develop anti-HPA-1a alloantibodies reacting with α β and/or β . Objectives/Patients/Methods To demonstrate this hypothesis, sera from HPA-1bb (n = 5) and HPA-1ab (n = 1) Gypsy GT patients were investigated by modified antigen capture assay using platelets or stable transfected cells. Furthermore, stable transfected cells expressing either α β or α β3 together with soluble monomeric chimeric β (as absorbent) were used to differentiate anti-β and anti-α β reactivity. Results Only HPA-1bb patients developed alloantibodies reacting with HPA-1a cells. Further analysis showed that HPA-1bb patients developed anti-HPA-1a alloantibodies reacting with β and/or α β . Conclusion In this study, we found that HPA-1bb patients who failed to express α β on the platelet surface can develop alloantibodies against HPA-1a reacting with β as well as α β . This is of particular importance as anti-HPA-1a alloantibodies might cause fetal neonatal alloimmune thrombocytopenia and/or platelet transfusion refractoriness