First evidence of subclinical renal tubular injury during sickle-cell crisis

International audienceBACKGROUND: The pathophysiologic mechanisms classically involved in sickle-cell nephropathy include endothelial dysfunction and vascular occlusion. Arguments demonstrating that ischemia-reperfusion injury-related kidney damage might coincide with vaso-occlusive crisis (VOC) are lacking. METHODS: In this prospective study, we sought to determine whether tubular cells and glomerular permeability might be altered during VOC. Urine neutrophil gelatinase-associated lipocalin (NGAL) levels and albumin-excretion rates (AER) of 25 patients were evaluated prospectively during 25 VOC episodes and compared to their steady state (ST) values. RESULTS: During VOC, white blood-cell counts (WBC) and C-reactive protein (CRP) were significantly higher than at ST but creatinine levels were comparable. Urine NGAL levels were significantly increased during VOC vs ST (P = 0.007) and remained significant when normalized to urine creatinine (P = 0.004), while AER did not change significantly. The higher urine NGAL concentration was not associated with subsequent (24-48 hour) acute kidney injury. Univariate analysis identified no significant correlations between urine NGAL levels and laboratory parameters during VOC. CONCLUSIONS: These results demonstrated that subclinical ischemia-reperfusion tubular injury is common during VOC and highlight the importance of hydroelectrolyte monitoring and correction during VOC

B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.

International audiencePrimary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. Rituximab, a B cell-depleting agent, has become the first-line treatment for ITP; however, patients with refractory disease usually require splenectomy. We identified antibody-secreting cells as the major splenic B cell population that is resistant to rituximab. The phenotype, antibody specificity, and gene expression profile of these cells were characterized and compared to those of antibody-secreting cells from untreated ITP spleens and from healthy tissues. Antiplatelet-specific plasma cells (PC) were detected in the spleens of patients with ITP up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the single-cell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature, including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected in untreated ITP spleens. These results suggest that the milieu generated by B cell depletion promotes the differentiation and settlement of long-lived PC in the spleen

The EHA Research Roadmap:Platelet Disorders

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1 to 2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cellbased Immune Therapies; and Gene Therapy

Br J Haematol

International audienc

CAUSES DE DECES DES ADULTES ATTEINTS D'UN SYNDROME DREPANOCYTAIRE MAJEUR

PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prévalence et signification clinique des anticorps antiphospholipidiques présents au diagnostic de patients atteints d'un purpura thrombopénique auto-immun

Le but de cette étude était d évaluer au moment du diagnostic de purpura thrombopénique auto-immun (PTAI), dans une large cohorte monocentrique, la fréquence et la signification de la présence d anticorps antiphospholipides (APL) [anticorps anti-cardiolipines (aCL) et anticoagulant circulant type lupique (ACC)] dont les chiffres sont actuellement controversés. Des APL ont été recherchés chez 215 adultes au moment du diagnostic de PTAI avec un nombre de plaquettes inférieur à 50x109/L. Or, la présence d'APL a été retrouvée chez 55 patients (26%) au diagnostic de PTAI : 42 (20%) avaient des IgG-aCL; 12 (6%) avaient des IgM-aCL sans IgG ; 1 avait un ACC isolé. Quinze malades avaient un ACC associé à des aCL. La présence d'un ACC était corrélée à un taux élevé d'IgG-aCL (>=40 U) (p=0,001). L âge, le sexe, le taux initial de plaquettes, le score hémorragique, l'évolution aiguë ou chronique du PTAI n'étaient pas associés à la présence d'APL, en dehors de l âge, plus bas en présence d un ACC (âge moyen : 29+-14 ans vs 45+-20 ans, p=0,002). Après un suivi médian de 31 mois, 14/215 (7%) patients ont thrombosé ; 4 étaient porteurs d'APL (IgG-aCL >=40 U toujours associés à un ACC). En analyse multivariée, l'apparition d'une thrombose était associée à l'âge (HR =1,6; IC95% 1,2-2,4), à la présence d'un ACC (HR=9,9; IC95% 2,3-43,4) ou à la présence d'un IgG-aCL à un taux >=40 U ) (HR=7,5; IC95% 1,8-31,5). En conclusion, la corrélation entre la présence d un ACC et d un taux important d IgG-aCL, et leurs associations à la survenue d une thrombose suggèrent que la recherche d APL au diagnostic de PTAI devrait être réalisée pour chaque patient au diagnostic.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Treatment of chronic immune thrombocytopenic purpura in adults

International audienceUntil recently, the management of refractory immune thrombocytopenic purpura (ITP) was a real challenge as shown by the large variety of treatments proposed in both American Society of Hematology and the British Committee for Standards in Haematology guidelines published 10 and 6 years ago, respectively. However, as in the past 5 years, new therapeutic approaches including eradication of in infected patients and rituximab have been proposed and the thrombopoietin-receptor agonists have been developed and licensed for ITP. It is likely that the therapeutic strategy of ITP will be profoundly modified and revisited in the next future. The purpose of this article is to discuss the impact and the place of these new therapeutic options into the whole treatment strategy of chronic ITP and to draw the perspective of new experimental therapies