Les patients atteints d’hémochromatose, via leurs associations, ont alerté les tutelles sur les difficultés de leur prise en charge du fait de la diminution des lieux susceptibles de les recevoir due à la fermeture de services hospitaliers et du peu de sites EFS habilités en tant que centre de soins. L’ARS IDF, des médecins hépato gastroentérologues, des associations de malades et l’EFS-IDF décident de mener une expérimentation pour faciliter les dons saignées dans 3 sites EFS, non habilités en tant que centre de soins, mais situés à proximité d’un service hospitalier traitant les patients atteints d’hémochromatose. L’arrêté du 21 septembre 2016 autorise l’expérimentation pendant 2 ans, une convention est signée sous l’égide de l’ARS entre les sites EFS et les services d’Hépatologie ou de Médecine Interne des hôpitaux Avicenne, Beaujon et HEGP.

Les thrombopénies immunologiques induites par des médicaments (TIMD) sont rares, mais profondes, survenant brutalement après l'administration d'un médicament auquel le patient a été préalablement exposé de façon répétée. De nombreux médicaments ont été incriminés. Nous avons décrit, en 2010, le premier cas de TIMD liée à la méthylprednisone (MP), et étudié depuis cinq autres cas. La recherche d'anticorps anti-médicament dépendant (DDAbs) a été réalisée en MAIPA (Monoclonal Antibody-specific Immobilization of Platelet Antigen assay) en présence de MP et d'autres médicaments reçus pouvant être suspectés, en comparaison de sérums « témoins ». Des tests d'adsorption/élution ont été réalisés chez deux patients. L'implication de la MP dans les TIMD, suspectée cliniquement, a été confirmée, chez les 6 patients, par la détection de DDAbs anti-GPIIbIIIa en présence de MP, non retrouvés en l'absence de médicament ou en présence de Dexaméthasone. Le patient décrit en 2010, atteint de sclérose en plaque, ne recevait aucun autre médicament. Les cinq autres patients étaient suivis en oncologie, et pour 3 d'entre eux, des DDAbs anti GpIIbIIIa à l'oxaliplatine et/ou au folinate de calcium ont également été identifiés, en cohérence avec l'étude approfondie des dossiers cliniques. Des tests croisés d'adsorption-élution suggèrent que ces DDAbs sont des anticorps distincts. Nous décrivons ici la première série de TIMD liées à la MP, et associées, pour trois d'entre elles, à des TIMD à l'acide folinique et/ou à l'oxaliplatine, suggérant, chez ces patients, une susceptibilité accrue à développer des anticorps avec plusieurs drogues.

The authors have disclosed no conflicts of interest.

There is growing concern regarding the risk of transfusion- transmitted (TT) hepatitis E. Since the first described case in 2006, several TT hepatitis E have been reported to the French hemovigilance network. We performed a retrospective analysis of all cases of TT hepatitis E reported between 2006 and 2016. Transfusion-transmitted hepatitis E with high imputability according to phylogenetic analysis occurred in 23 patients aged 8 to 88 years and involved mostly solid organ recipients (n = 9) or patients with malignant hematological diseases (n = 9, including 4 hematopoietic allograft recipients). Involved blood products were plasma (n = 7), among which 6 had undergone pathogen reduction with solvent/detergent (n = 4) or amotosalen + ultra-violet A (UVA) (n = 2 from 1 donation) treatments, red blood concentrates (n = 7), apheresis platelets concentrates (n = 3) and whole blood pooled platelets concentrates (n = 6), among which one had underwent amotosalen + UVA treatment. Median hepatitis E virus (HEV) RNA dose infused was 5.79 [4.36-10.10] log IU. HEV infection progressed to chronic hepatitis E in 14 (61%) immunocompromised patients, 2 of whom had advanced liver fibrosis at diagnosis. Chronic hepatitis E patients cleared HEV with ribavirin treatment (n = 10), after immunosuppressive drug reduction (n = 3), or spontaneously (n = 1). One additional organ transplant recipient with associated co-morbidities died with ongoing HEV infection and multiple organ failure. The other 8 (34.8%) patients with TT hepatitis E cleared HEV within 6 months with ribavirin treatment (n = 3), reduced immunosuppression (n = 1) or spontaneously (n = 4). Red cells, platelets, and plasma transfusions may be associated with TT hepatitis E that can evolve to chronic hepatitis E in immunocompromised patients. Hepatitis E virus has emerged in France as a clinically significant TT infection risk.

Drug-induced immune thrombocytopenia (DITP) is a rare but severe drug side effect caused by antibodies that bind platelets only in the presence of a drug. Drug-dependent antibodies (DDabs) usually target platelet-specific glycoproteins (Gp), such as GpIIb/IIIa or GpIb/IX.1, 2 About a 100 different drugs have been linked to DITP.3 Immune severe thrombocytopenia occurs quickly after the administration of the drug, following an extended period of well-tolerated drug administration, and resolves within 1 to 10 days after drug withdrawal. We describe six patients who experienced severe thrombocytopenia due to methylprednisolone (MP) DITP. We retrospectively analyzed the medical records of six patients for whom blood samples were sent to the Platelet Immunology Laboratory of the EFS (Henri Mondor Hospital, Creteil, France) for suspected MP-induced thrombocytopenia. Anti-platelet antibodies were searched with the monoclonal antibody-specific immobilization of platelet antigen (MAIPA) assay (ApDia, Turnhout, Belgium),4 in the presence and absence of the drug (see supplemental data). Sera were tested against immobilized GpIIb/IIIa, GpIb/IX and GpIa/IIa. No anti-platelets antibodies were detected in the 6 patient's serum in the absence of drugs, when DDabs targeting GpIIb/IIIa were identified in the presence of drugs (see below). No DDAbs directed against GpIb/IX or GpIa/IIa were detected in presence or absence of drugs (Table 1). The three first patients were treated with MP, one for a multiple sclerosis (yet reported5) and two for premedication for chemotherapy (FOLFOX$) for the treatment of cancer. They all presented acute and severe thrombocytopenia immediately after administration of MP, that resolved in 6 to 48 hours. For all, the readministration of the MP link to recurrence of thrombocytopenia that did not reappear after the eviction of MP. One of them (patient number 2) needed to be transferred to the intensive care unit because of massive hematuria. Serum samples from the patients were tested with several suspected drugs, and only GpIIb/IIIa DDAbs in the presence of MP were detected (Table S1). The fourth patient was a 64-year-old man with colorectal cancer previously treated from 2003 to 2010, with intermittent FOLFOX chemotherapy without complication. From June 2010 to August 2012, he presented eight episodes of acute thrombocytopenia. Six were attributed to one drug (MP (n = 3), oxaliplatin (n = 2) or leucovorin (n = 1)) and two were attributed to oxaliplatin and/or either MP or leucovorin. A blood sample collected following the first episode of DITP contains GpIIb/IIIa-specific DDabs in the presence of MP and oxaliplatin (Table S2). Unfortunately, no blood sample collected at the moment of leucovirin DITP was available to search leucovirin DDAbs. The fifth patient was a 75-year-old man with cystadenocarcinoma treated with intermittent fortnightly infusions of fluorouracil (FU), leucovorin and oxaliplatin with premedication based on MP and ondansetron (FOLFOX) without complication from 2014 to 2017. From July 2017 to November 2017, he presented seven episodes of acute thrombocytopenia that resolved spontaneously in less than a week after drug withdrawal. Four episodes occurred after MP (one with oxaliplatin), and three after leucovorin administration (one with oxaliplatin). Blood samples contained GpIIb/IIIa DDabs in the presence of MP and leucovorin (Table S3). One serum was adsorbed into platelets in the presence of MP and leucovorin separately. Both eluates and adsorbed serum were then tested by MAIPA in the presence or absence of the drugs. Only antibodies specific for the drug used in the adsorption procedure were detected in the eluates, indicating the presence of different DDabs rather than a single antibody cross-reacting with multiple drugs (Table S4). The sixth patient was a 49-year-old woman with colon cancer diagnosed in January 2010 and treated with 26 cycles of FOLFOX without complication. The first episode of DITP occurred in February 2011, after the administration of oxaliplatin following premedication with MP and ondansetron. Oxaliplatin was then replaced with irinotecan with MP as premedication, but the patient's platelet count fell again (1 × 109 G/L) after the first administration. Eight other episodes of DITP occurred between June 2011 and October 2015. Each administration of oxaliplatin resulted in thrombocytopenia. The other DITPs appeared after the administration of either MP or leucovorin. However some treatments with MP (2012) or leucovorin (2015) had no effect on platelet count. Blood samples from March 2011 and November 2011 contained GpIIb/IIIa-specific DDabs in the presence of MP, oxaliplatin and leucovorin (Table S5). Finally, sera of six other patients receiving FOLFOX with MP premedication but without thrombocytopenia were tested as controls. No DDAbs in the presence of MP, dexamethasone (DXM), oxaliplatin, ondansetron or leucovorin were found. Then, our series contained six patients presenting DITP due to MP. All patients had anti-GpIIb/IIIa DDabs only highlighted in the presence of MP, and these antibodies did not cross-react with DXM. Three patients also presented DITP linked to leucovorin and/or oxaliplatin, with different and specific DDabs detected in the presence of these drugs. Five of the six patients were treated with platinum-based chemotherapy for gastrointestinal or urinary tract cancer, and all had a prolonged event-free period of prior exposure to MP. All patients experienced immunoallergy-like symptoms (chills and/or fever) during the drug administration, that lead to severe thrombocytopenia. In all episodes, platelet count recovered spontaneously within a few days after drug withdrawal. In five of the six patients (the exception being patient six), the episodes of sudden thrombocytopenia and the presence of DDabs were perfectly correlated, providing evidence for the specificity of the reaction. Oxaliplatin-induced DITP have been widely described6 and considered as often responsible for DITP and other autoimmune cytopenia in cancer. Curtis et al. reported two patients treated for cancer with platinum-based chemotherapy with premedication based on DXM (more widely used than MP in USA) that presented oxaliplatin associated DDabs.7 However since DXM, leucovorin and irinotecan DDabs were also detected, both cases could also be attributed to DXM induced DITP. Furthermore only four of our patients had been treated with oxaliplatin before the first episode of DITP, and only two of these patients presented DDabs in the presence of oxaliplatin. We described the first serie of DITP related to MP. Physicians should be aware that in patients with cancer, drugs other than oxaliplatin, such as MP may induce DITP, sometimes with the simultaneous production of multiple DDabs. Addendum: during the writing of this article, a seventh case of MP-induced thrombocytopenia was referred to our laboratory, with DDAbs associated with MP, oxaliplatin and leucovorin. Dr Camille Jung, Dr Isabelle Cojean-Zelek and Dr Sandrine Lacour, Dr Hassina Mimoune, Dr Nouara Arab. None of the authors declared conflict of interest. M.D. designed research, monitored the database, analyzed data, and wrote the manuscript, E.LT. perfomed biological analysis, and contributed to the writing of the manuscript, L.C. supervised biological analysis, analyzed data and contributed to the writing of the manuscript, L.T. analyzed the data and contributed to the writing of the manuscript, M.D. included a patient and approved the manuscript, A.F. included a patient and approved the manuscript, R.H. included a patient and approved the manuscript, B.LV. included a patient and approved the manuscript, J.P.M. included a patient and approved the manuscript, J.B.M included a patient and approved the manuscript, M.M. verified and analyzed the data, contributed to the writing of the manuscript, M.M. verified and analyzed the data and contributed to the writing of the manuscript, P.B. designed research, verified and analyzed the data, supervised biological analysis and the writing of the manuscript. Table S1 Medical history of the first three patients described above Table S2: Chronology of multiple drug administrations and DITP episodes (patient #4) Table S3: Chronology of multiple drug administrations and DITP episodes (patient #5) Table S4: Adsorption-elution analysis in patient #5 Table S5: Chronology of multiple drug administrations and DITP episodes (patient #6) Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Additional supporting information may be found online in the Supporting Information section at the end of the article. Data S1. Supplementary material. Table SI. Patient baseline characteristics. Table SII. Baseline characteristics of patients with stable disease as best response to pembrolizumab (10 mg/kg Q2W and 200 mg Q3W groups pooled). Table SIII. Adverse events occurring in at least two patients. Figure S1. CONSORT (study flow) diagram. Q2W, every 2 weeks; Q3W, every 3 weeks. Figure S2. Kaplan-Meier estimates of duration of stable disease based on International Myeloma Working Group uniform response criteria per site review. Figure S3. Change from baseline in maximum M-protein or free light chain in the 27 of 30 patients for whom data were evaluable. Figure S4. Kaplan-Meier estimates of (A) progression-free survival and (B) overall survival based on International Myeloma Working Group uniform response criteria per site review.

Les Thrombasthénies de Glanzmann (GT), syndromes de Bernard et Soulier (BS), et patients déficitaires en GPIV/CD36 (CD36NEG) peuvent développer des isoanticorps après transfusions ou grossesses. Le MAIPA est la technique de référence pour identifier auto et allo anticorps (Acs) anti plaquettes dans tous les contextes. Le Luminex© (PakLx©) a été conçu pour la détection des allo anti-HPA− 1 à − 5 et des anti CD36 uniquement. Nous montrons ici l'intérêt du PakLx© pour l'identification des anti-GPIIbIIIa, -GPIbIX et -CD36 chez les patients déficitaires en ces glycoprotéines. Soixante quinze sérums de GT, 12 de BS, 18 de patients CD36NEG (10 mères de thrombopénies néonatales et 8 drépanocytaires), ont été étudiés parallèlement en MAIPA et en PakLx, et confrontés aux dossiers transfusionnels ou obstétricaux. Les résultats étaient concordants pour 74 % des sérums de GT et BS, et 56 % des patients CD36 NEG. Les discordances franches, rares dans les GT et BS (3/87), sont plus fréquentes dans les déficits en CD36 (5/18), le plus souvent en faveur d'une positivité isolée en PakLx. De plus, des traces d'Acs, validées par l'évolution clinico biologique, sont fréquemment retrouvées par une seule des 2 techniques (22 % des sérums de notre étude), soit en PakLx (pour 2/3), soit en MAIPA (pour 1/3), avec un profil reproductible chez un même patient. Le PakLx© est un outil très performant dans ce contexte, en particulier pour la détection de traces d'iso-anticorps, utile pour la prise en charge transfusionnelle et/ou obstétricale de ces patients. Mais, il ne peut se substituer au MAIPA, qui dans notre étude était isolément contributif dans 10 % des cas.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in 1/800-1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. The most feared complication of this disorder is intracranial hemorrhage, leading to death or neurological sequelae. There is no systematic screening of at-risk pregnancies and FNAIT is often discovered when fetal or neonatal bleeding is observed. A working group on fetomaternal platelet alloimmunization was created in 2017, under the auspices on the French Group of Thrombosis and Hemostasis (GFHT). The first objective of this group was to survey clinical practices for treatment of thrombocytopenic neonates in a context of suspected or confirmed FNAIT.

To the Editor: In many countries, splenectomy remains the gold standard treatment for severe immune thrombocytopenia (ITP) and a second-line treatment for warm antibody autoimmune hemolytic anemia (wAIHA). Splenectomy is an independent risk factor of venous thromboembolism throughout life. Postulated mechanisms include thrombocytosis and circulation of damaged cells or microvesicles due to the removal of the blood filter. Splenectomy also favors portal or splenic vein thrombosis (PSVT) in the early postoperative period. Local factors such as inflammation, decreased portal flow during peritoneal exsufflation and stasis in the splenic stump may play a role. Whereas symptomatic PSVT is rare (2% of patients undergoing splenectomy regardless of the indication), systematic CT-scan has revealed PSVT in up to 55% of patients after splenectomy. In contrast, few clinical complications of PSVT are reported on long-term follow-up of such patients (3 portal cavernomas reported in 83 patients splenectomized for ITP), which raises the question of the clinical significance of asymptomatic PSVT. Complications such as portal cavernoma and mesenteric venous ischemia are respectively associated with extrahepatic portal vein thrombosis (ePVT) and proximal splenic vein thrombosis (pSVT) but the significance of thrombosis occurring in intrahepatic branches or distal splenic vein is uncertain. The natural history of postoperative PSVT is unclear, and thus no guidelines are established about their screening and treatment. We conducted a retrospective study to assess the incidence, sites and outcome of PSVT in ITP and wAIHA patients who underwent systematic enhanced CT-scan after splenectomy. The study was performed in accordance with the Helsinki Declaration and conducted between January 2009 and April 2015 in Henri Mondor Hospital (Creteil, France), a tertiary-care national referral center for adult immune cytopenias, where abdominal enhanced CT-scan was systematically performed between days 3 and 7 after splenectomy. Adult patients splenectomized for ITP or wAIHA were consecutively included. Patients with immune cytopenia secondary to hematologic malignancy were excluded. Most patients had undergone a preoperative CT-scan; none showed PSVT. The postoperative CT-scan was assessed by an independent senior radiologist. SVT was defined as pSVT when located between the superior and inferior mesenteric vein (SMV and IMV) or within 2 cm from the SMV junction; otherwise, it was defined as distal SVT (dSVT). PVT was classified as intrahepatic or extrahepatic. Patients received postoperative thromboprophylaxis by low molecular weight heparin. In case of PSVT the physician was free to initiate an anticoagulation therapy or to keep the patient on prophylactic regimen. Doppler ultrasonography or enhanced CT-scan was performed within the 6 months after PSVT. The response to splenectomy was defined according to international criteria for ITP and as hemoglobin>10 g/dL for wAIHA. Thirty nine patients (20 women characteritics described in Supporting Information Table S1) were included among 43 patients screened; splenectomy was mainly performed by laparoscopy (n538) for patients with ITP (n530) or wAIHA (n59). The median time from diagnosis of cytopenia to splenectomy was 18 months [IQR: 10–56]. The median age of the patients was 43 years [IQR: 33–55]. Eight patients were positive for antinuclear antibodies, including 2 with systemic lupus erythematosus. Lupus anticoagulant or anticardiolipin antibody was detected in 5/39 patients without definite antiphospholipid syndrome. Patients had received a median of 4 lines [IQR: 3–5] of treatment. In the month before splenectomy, 22/30 (75%) ITP patients received corticosteroids, 13/30 (43%) intravenous immunoglobulins (IVIg) and 12/30 (40%) thrombopoietin receptor agonists (TPO-RAs); the median preoperative platelet count was 733 10/L [IQR: 31–139]. 63% of ITP patients and 89% of wAIHA responded to splenectomy; the relapse rate was 13% in ITP and 44% in wAIHA. CT-scan was performed at a median of 5 days [IQR: 4–6] after splenectomy. The overall incidence of PSVT was 74% (29/39), without significant difference between ITP and wAIHA (P5 .79). The characteristics of PSVT are in Figure 1 and in Supporting Information Table S2. Most of the SVT cases were distal (n522/28). Most of the PVT cases were intrahepatic (n514/15); 3 involved the left or right portal branch. One ePVT occurred in a patient with history of recurrent pulmonary embolism. Only 5 patients had clinical symptoms at the time of the PSVT [i.e., abdominal pain (5/5) and fever (1/5)]; symptomatic PSVT cases were iPVT associated with dSVT (n53) and isolated dSVT (n52). We found no association between PSVT occurrence and the age, sex, positivity for antinuclear antibodies, use of TPO-RAs or IVIg, corticosteroids dose, preoperative or postoperative platelet count, which may be explained by the small number of patients. In accordance with other studies, spleen weight was higher in patients with PSVT (mean 206 vs 102 g, P5 .14). According to the physician decision, 13/25 patients received anticoagulation therapy for a median of 8 weeks [range: 4–18] and 12/25 patients (including 2 pSVT, 10 dSVT, 4 segmental iPVT) received standard thromboprophylaxis. Radiological follow-up was performed at a median of 6 weeks [IQR: 2–26], mostly by CT-scan (17/25). Eight patients (62%) who received curative anticoagulation showed complete resolution of the thrombus, as did all 12 untreated patients. Portal cavernoma developed in a woman with wAIHA despite curative

BACKGROUNDSickle cell disease (SCD) patients undergo multiple red blood cell (RBC) transfusions and are regularly exposed to low-prevalence (LP) antigens specific to individuals of African descent. This study evaluated the prevalence of antibodies against LP antigens in SCD patients and the need to identify these antibodies in everyday practice. STUDY DESIGN AND METHODSPlasma from 211 SCD patients was tested with RBCs expressing the following LP antigens: RH10 (V), RH20 (VS), RH23 (D-W), RH30 (Go(a)), KEL6 (Js(a)), and MNS6 (He). RESULTSNine LP antibodies were found in eight patients (3.8%): five anti-RH23, two anti-RH30, and two anti-MNS6. The exposure risk, calculated for each LP antigen, was below 3% per RBC unit, for all antigens tested. Thus, in this cohort of transfused SCD patients, the prevalence of LP antibodies was similar to that of antibodies against antigens of the FY, JK, and MNS blood group systems. These findings also reveal the occurrence of anti-RH23 in SCD patients. No anti-RH20 or anti-KEL6 were found, despite the high frequency of mismatch situations. CONCLUSIONThese results highlight the immunogenicity of these LP antigens, and the evanescence of antibodies against LP antigens. They also highlight the importance of appropriate pretransfusion testing for patients frequently transfused, who are likely to be exposed to multiple types of blood group antigens.

Degenerative disc disease involves sequential events that lead to the loss of cells, a decrease in disc matrix production, disc dehydration, and alteration of its biomechanical properties. The aim of this study was to determine whether cryoinjury of the nucleus pulposus performed through endplate perforation contributes to disc degeneration and to compare this technique with standard methods. Under general anesthesia, the lumbar discs of six pigs were exposed and randomly submitted to needle puncture of the annulus fibrosus (NeP), isolated endplate injury (EP), or cryoinjury using a 2.5-J Thompson cryoprobe applied through a single endplate perforation (EP+cryo). The remaining discs served as controls. Animals were sacrificed at two months and the harvested lumbar spines were submitted to CT scan and MRI investigations. Histologic analysis was performed to assess the degree of disc degeneration. CT scan showed that decrease in average disc height was more important after cryoinjury (49.3%) than after endplate perforation (16.9%) (P < 0.0001) or needle puncture (19.4%) (P < 0.0001). On MRI, the dehydration ratio was significantly more important after EP+cryo (60%) than after NP (40%) or EP (30%) (P < 0.0001). After cryoinjury, the histologic score developed for this study was significantly higher than after needle puncture or endplate perforation (P < 0.0001). Imaging and histological analysis showed that disc cryoinjury applied through endplate perforation was superior to the classical NeP and EP models to induce experimental disc degeneration. This model appears suitable for testing safety and efficacy of novel treatments of intervertebral disc degeneration.

Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody (autoAb)-mediated immune disorder that affects both children and adults.[1][1]–[3][2] The pathology of the disease is caused by immunoglobulin G (IgG)-, IgM, or IgA-type autoAbs associated, or not, with molecules of the complement

TransfusionVolume 57, Issue 4 p. 1089-1091 REPORT OF NEW ALLELES OR ANTIGENS Molecular characterization of 13 new RHD alleles Aline Floch, Aline Floch Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorAurelie Barrault, Aurelie Barrault Etablissement Français du Sang Île de FranceSearch for more papers by this authorAlexandre G. De Brevern, Alexandre G. De Brevern orcid.org/0000-0001-7112-5626 Laboratoire d'Excellence GRex, Paris, France INSERM U1134, Dynamique des Structures et Interactions des Macromolécles Biologiques INSERM UMR_S 1134, Université Paris Diderot, Sorbonne Paris Cité Institut National de la Transfusion Sanguine, Paris, FranceSearch for more papers by this authorJennifer Martret, Jennifer Martret Etablissement Français du Sang Île de FranceSearch for more papers by this authorKevin Gaillard, Kevin Gaillard Etablissement Français du Sang Île de FranceSearch for more papers by this authorLaurent Devaux, Laurent Devaux Etablissement Français du Sang Île de FranceSearch for more papers by this authorBtissam Chami, Btissam Chami Etablissement Français du Sang Île de FranceSearch for more papers by this authorPhilippe Bierling, Philippe Bierling Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorFrance Pirenne, France Pirenne Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorChristophe Tournamille, Corresponding Author Christophe Tournamille christophe.tournamille@efs.sante.fr Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, FranceAddress reprint requests to: Christophe Tournamille, Laboratoire IHM, Etablissement Français du Sang, Bâtiment UITC, Centre Félix Reyes, 2e étage, 5 rue Gustave Eiffel, 94000 Créteil, France; e-mail: christophe.tournamille@efs.sante.fr.Search for more papers by this author Aline Floch, Aline Floch Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorAurelie Barrault, Aurelie Barrault Etablissement Français du Sang Île de FranceSearch for more papers by this authorAlexandre G. De Brevern, Alexandre G. De Brevern orcid.org/0000-0001-7112-5626 Laboratoire d'Excellence GRex, Paris, France INSERM U1134, Dynamique des Structures et Interactions des Macromolécles Biologiques INSERM UMR_S 1134, Université Paris Diderot, Sorbonne Paris Cité Institut National de la Transfusion Sanguine, Paris, FranceSearch for more papers by this authorJennifer Martret, Jennifer Martret Etablissement Français du Sang Île de FranceSearch for more papers by this authorKevin Gaillard, Kevin Gaillard Etablissement Français du Sang Île de FranceSearch for more papers by this authorLaurent Devaux, Laurent Devaux Etablissement Français du Sang Île de FranceSearch for more papers by this authorBtissam Chami, Btissam Chami Etablissement Français du Sang Île de FranceSearch for more papers by this authorPhilippe Bierling, Philippe Bierling Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorFrance Pirenne, France Pirenne Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, France Université Paris Est-Créteil, Créteil, FranceSearch for more papers by this authorChristophe Tournamille, Corresponding Author Christophe Tournamille christophe.tournamille@efs.sante.fr Etablissement Français du Sang Île de France Institut National de la Santé et de la Recherche Médicale (INSERM)-U955, Equipe 2: Transfusion et Maladies du Globule Rouge, Institut Mondor de Recherche Biomédicale, Créteil, France Laboratoire d'Excellence GRex, Paris, FranceAddress reprint requests to: Christophe Tournamille, Laboratoire IHM, Etablissement Français du Sang, Bâtiment UITC, Centre Félix Reyes, 2e étage, 5 rue Gustave Eiffel, 94000 Créteil, France; e-mail: christophe.tournamille@efs.sante.fr.Search for more papers by this author First published: 28 January 2017 https://doi.org/10.1111/trf.14004Citations: 2 This work was funded by the Etablissement Français du Sang, France. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume57, Issue4April 2017Pages 1089-1091 RelatedInformation

Thus far, only two studies have investigated seasonal variations of primary immune thrombocytopenia (ITP) incidence in children. Results have shown a temporally correlated increase in ITP incidence during the spring and early summer [ 1 Cohn J. Thrombocytopenia in childhood: an evaluation of 433 patients. Scand J Haematol. 1976; 16: 226-240 Crossref PubMed Scopus (41) Google Scholar , 2 Kühne T. Imbach P. Bolton-Maggs P.H. Berchtold W. Blanchette V. Buchanan G.R. Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. Lancet. 2001; 358: 2122-2125 Abstract Full Text Full Text PDF PubMed Scopus (222) Google Scholar ]. We recently assembled a cohort of incident ITP patients within the national French insurance claim database between 2009 and 2011 (n = 3771) [ [3] Moulis G. Palmaro A. Montastruc J.-L. Godeau B. Lapeyre-Mestre M. Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014; 124: 3308-3315 Crossref PubMed Scopus (199) Google Scholar ]. This population-based study demonstrated a peak of ITP incidence in January and a nadir in August among both children (aged <15 years) and adults [ [3] Moulis G. Palmaro A. Montastruc J.-L. Godeau B. Lapeyre-Mestre M. Sailler L. Epidemiology of incident immune thrombocytopenia: a nationwide population-based study in France. Blood. 2014; 124: 3308-3315 Crossref PubMed Scopus (199) Google Scholar ].

Alloimmunization against RBCs can cause life-threatening delayed hemolytic transfusion reactions. Anti-CD20 Ab has recently been used to prevent alloimmunization. However, its effects remain unclear, particularly in lymphoid organs. We investigated the impact of murine anti-CD20 Ab in the blood and spleen. We assessed protocols for preventing primary alloimmunization and for abolishing established alloimmunization. Prophylactic protocols prevented alloimmunization. However, anti-CD20 treatment could only limit the further amplification of established alloimmunization. Residual B cell subtype distribution was disrupted in the spleen, but adoptive transfer studies indicated that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major effect on alloreactive CD4+ T cells, increasing the expansion of this population and its CD40 expression, while lowering its CD134 expression, thereby confirming its role in alloimmunization. In conclusion, this study shows that anti-CD20 immunotherapy can prevent RBC Ab development. However, this immunotherapy is limited by the increase in alloreactive CD4+ T lymphocytes. Nevertheless, treatment with anti-CD20 Abs should be considered for patients requiring transfusion with a very high risk of alloimmunization and life-threatening complications.

BACKGROUND:Red blood cell (RBC) Thomsen-Friedenreich antigen exposure (T activation) in infants with necrotizing enterocolitis (NEC) has occasionally been associated with posttransfusional intravascular hemolysis thought to be due to anti-T antibodies in the donor plasma.STUDY DESIGN AND METHODS:We describe an infant with NEC and Clostridium perfringens infection complicated by severe hemolysis after plasma transfusion. After this case, infants with confirmed NEC were prospectively evaluated for T activation. We checked for hemolysis in patients with T activation receiving plasma-containing blood products.RESULTS:The infant had received 80 mL of fresh-frozen plasma (FFP). His RBCs displayed strong T activation, and agglutination was observed with four of six ABO-compatible FFP units. A direct antiglobulin test was negative. IgM-class anti-T antibodies were present in small amounts (titer of 8) in the transfused FFP. Anti-T antibodies from the blood donor were not hemolytic in vitro. In the prospective study, T activation was observed in three of 28 infants with NEC (11%). One infant presented moderate T activation and two infants presented very strong T activation but only moderate decreases in sialic acid expression on the RBC membrane. These three infants presented no signs of hemolysis after transfusion with unwashed blood products or FFP.CONCLUSION:Anti-T antibodies are unlikely to be the etiologic factor for the hemolytic reactions observed in infants with NEC and T activation. Massive RBC desialylation and the direct action of bacterial toxins are more probable causes. Strict avoidance of plasma-containing blood products does not seem justified in these infants.

Une thrombopénie fœtale et/ou néonatale (FMAIT) peut compliquer une allo-immunisation antiplaquettaire maternelle. Celle-ci peut être sévère et compliquée par une hémorragie intracrânienne (HIC – 10 % des cas). L'HIC est observée quasi exclusivement avec des anti-HPA1a. La récurrence d'une grossesse à l'autre, en règle, alors plus sévère, est le facteur pronostique de l'occurrence de la FMAIT. La ponction de sang fœtale pour déterminer le chiffre de plaquettes fœtale n'est plus pratiquée du fait de ses risques. Le traitement maternel par immunoglobulines intraveineuses (IgIV) hebdomadaire est le seul traitement reconnu capable de corriger la FMAIT. Si le père est hétérozygote HPA1a + b+, la détermination du phénotype HPA1 fœtal par recherche de cellules HPA1a dans le sang maternel ou par ponction amniotique est requise. La date de début de traitement et sa posologie ne sont pas consensuelles : entre la 18e et la 27e semaine d'aménorrhée et de 0,5 g à 5 g/kg/semaine selon les équipes et la gravité suspectée de la FMAIT. Des échographies transfontanellaires régulières et un repos de la mère sont indispensables. Un traitement par corticoïdes (0,5 à 1 mg/kg) en fin de grossesse est la règle, mais son efficacité contestée. Un accouchement prématuré (à partir de 24/35 SA) et/ou une césarienne systématique sont proposés par certains, contestés par d'autres. Le traitement par Ig IV est efficace dans 70 % des cas et pourrait prévenir l'HIC dans presque 100 % des cas. Si le nouveau-né naît avec moins de 30 G/L plaquettes, des transfusions HPA compatibles éventuellement cry-préservées ou non phénotypées si indisponibles sont indiqués ainsi qu'un traitement par Ig IV.

BACKGROUNDRed blood cell (RBC) storage in blood banks is not exempt from cellular injury. Alterations not observed on RBCs freshly isolated from units can rapidly appear in circulation. The transfusion of old blood units, even if this is a controversial issue, could therefore have adverse effects on the recipient. We wanted to determine the respective effects of storage duration and recipient plasma on RBCs for transfusion into patients with severe sepsis.STUDY DESIGN AND METHODSEleven stored RBC units were sampled at various time points, approximately Days 3 to 8 (referred to as fresh RBCs) and Days 38 to 42 (old RBCs) and tested in coincubation experiments with plasma obtained from 13 patients with severe sepsis and 17 healthy donors as controls. RBCs were tested after 24 or 48 hours at 37°C for the detection of senescence markers (phosphatidylserine exposure, calcium influx, and reactive oxygen species detection and decrease in size) with or without exposure to plasma.RESULTSWe confirmed that a 42‐day refrigerated storage of RBCs alone (without any incubation in plasma) had no significant effect on RBCs and no senescence marker detected. By contrast, ex vivo exposure to plasma samples altered both fresh and old RBCs, with a much larger effect for old RBCs, regardless of the plasma used (sepsis vs. control).CONCLUSIONWe show that the main factor affecting the senescence of RBCs for transfusion into patients with severe sepsis is the age of the stored units rather than the clinical status of the recipient.

BACKGROUNDTransfusion‐transmitted bacterial infection (TTBI) is still one of the most feared complications of blood transfusion.CASE REPORTWe report a fatal case involving an 8‐year‐old child with congenital dyskeratosis complicated by severe aplastic anemia who was regularly transfused with platelet (PLT) concentrates for 5 years. The patient received an apheresis PLT concentrate (APC) on Day 0 due to thrombocytopenia complicated by mucocutaneous hemorrhage. Thirty minutes after the start of the transfusion, bradycardia and dyspnea appeared, quickly followed by chills, nausea, vomiting, headache, and hyperthermia. TTBI was suspected and the patient was immediately treated with intravascular antibiotherapy. On Day 3, the patient developed severe acute respiratory distress syndrome leading to death on Day 7. Patient blood cultures and APC cultures were both positive for Citrobacter koseri.RESULTSThe donor was a 19‐year‐old woman. She had previously given blood. No infectious symptom was reported during the medical interviews before and after the donation and no postdonation information was received. On the day of the donation (Day −2), her white blood cell count was 5.83 × 109/L. She came back on Day 8 to undergo additional tests. The cultures from blood, stool, urine, the skin of the inside of the elbow at the point of needle insertion, and ear samples were all negative for C. koseri. However, a nasal sample was positive for C. koseri.CONCLUSIONThe isolates from the donor's blood cultures, the APC bag, the attached tube, and the donor's nasal sample all gave identical profiles; they were thus identified as the same strain and the TTBI was confirmed.