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Summary: Various hematological pathologies have been described in association with antiphospholipid syndrome (APS). Thrombocytopenia is frequently found in APS patients, its incidence has ranged from 22–42% in different series, it is usually moderate (>50×109/L) without clinical manifestation and requires no intervention. A high percentage of patients with isolated idiopathic thrombocytopenic purpura have antiphospholipid antibodies, however the pathogenetic role and the clinical importance of these antibodies in this condition is still not clear. Other hematological manifestations reported in association with APS include: bone marrow necrosis, and various thrombotic microangiopathic syndromes such as: thrombotic thrombocytopenic purpura, hemolytic-uremic syndrome, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, and catastrophic APS. A high index of suspicion is needed for the early recognition and treatment of these conditions. [Copyright &y& Elsevier]

Abstract: Severe autoimmune thrombocytopenic purpura is now commonly treated with high doses of intravenous immunoglobulins (IVIGs). Twenty-four years after this treatment was first demonstrated to be effective, several questions remain to be resolved. We review here current knowledge concerning the frequency and type of side effects and the likely mechanism of action of IVIGs. We suggest that the currently recommended dose of IVIG (2 g/kg) could be halved, that the total dose of IVIG should be administered as a single infusion, that nonresponders could be provided another equal dose on day 3, and that IVIG plus prednisolone should be considered the gold standard for treatment of the most severe forms of the disease. Treatment with anti-D immunoglobulin could be proposed as an alternative if the results recently obtained with high doses (75 µg/kg) are confirmed. Finally, because IVIG has only a transient effect, it cannot be considered a curative treatment for patients with chronic autoimmune thrombocytopenic purpura. [Copyright &y& Elsevier]

The CARMEN-France registry is a prospective, multicenter registry in France including adult patients with a new diagnosis of immune thrombocytopenia or of autoimmune immune hemolytic anemia (2402 patients included in December 31, 2023). The recording of clinical, biological and treatment data allows detailed epidemiological and pharmacoepidemiological real-world studies. This review summarizes the CARMEN-France registry protocol, gives examples of studies conducted in the registry, and indicates future directions such as inclusion of patient reported outcomes, linkage with the French national health insurance database and linkage with other registries in Europe. [ABSTRACT FROM AUTHOR]

• Immune thrombocytopenia (ITP) in association with systemic sclerosis has been rarely reported. • In the context of new onset thrombocytopenia, ITP must be distinguished from scleroderma renal crisis and thrombotic thrombocytopenic purpura. • Rituximab in association with thrombopoeitin growth factors may be considered in ITP that does not respond to first-line treatment with corticosteroids and/or intravenous immunoglobulins. • Splenectomy can be proposed in case of life-threatening bleeding. Thrombocytopenia in the context of systemic sclerosis (SSc) is rare. It should primarily raise the possibility of scleroderma renal crisis. Immune thrombocytopenia (ITP) is another cause of low platelets that is common in systemic lupus erythematosus, but tremendously rare in patients with SSc. We herein report two cases of severe ITP in patients with SSc. The first case is a 29-year-old woman with very low platelet counts (2 × 109/L) that did not increase despite receiving corticosteroids, intravenous immunoglobulins (IVig), rituximab and romiplostim. Because of a symptomatic acute subdural haematoma, emergency splenectomy was performed and subsequently platelet counts normalised without neurological sequelae. The second case is a 66-year-old woman in whom self-limited mild epistaxis revealed low platelet counts (8 × 109/L). The patient did not improve after the use of IVig and corticosteroids. Secondarily rituximab and romiplostim normalised the platelet counts after 8 weeks. To the best of our knowledge this is the first reported case of severe ITP in a patient with diffuse cutaneous SSc and anti-topoisomerase antibodies. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8 + T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In this review, the major mechanisms leading to thrombocytopenia, the role of the different immune cells and the different targets of treatments are described. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (aPL) are common in ITP, but their role for the occurrence of ITP-related thrombosis is controversial. We performed a systematic review and a meta-analysis to investigate the risk of thrombosis associated with lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β 2 GP-I antibodies in primary ITP. The literature search was run on Medline, Cochrane and ISI Web of Science from January 1st 1980 to December 31st 2014. Unpublished studies were searched in meeting abstracts. The main analysis assessed the risk of all thromboses (arterial or venous) associated with the presence of LA, aCL or anti-β 2 GP-I antibodies. Random-effect models were used to calculate odds ratios (OR) and their 95% confidence intervals (CI). Searches in electronic databases retrieved 776 citations. Twelve additional studies from unpublished literature were added. Eventually, 10 cohort studies totalizing 1574 patients were included in the analysis. The pooled OR for the risk of all thromboses associated with LA was 6.11, 95% CI [3.40–10.99]; it was 2.14, 95% CI [1.11–4.12] with aCL. The ORs were similar when stratifying on the type of thrombosis (arterial vs. venous). Only two studies assessed the risk of thrombosis associated with anti-β 2 GP-I antibody positivity; consequently, no pooled OR was computed for these antibodies. This meta-analysis highly suggests that LA positivity, and to a less extent aCL antibodies, are associated with an enhanced risk of thrombosis in primary ITP patients. Further prospective studies are needed to identify the factors associated with the risk of thrombosis among LA patients before assessing prevention strategies. [ABSTRACT FROM AUTHOR]

Introduction B-cell depletion with rituximab (RTX) is widely used to treat autoimmune diseases, especially as second-line therapy for immune thrombocytopenia (ITP). The incidence of RTX-induced hypogammaglobulinemia is unknown because of heterogeneous follow-up and confounding factors such as concomitant immunosuppressive treatments in most patients. We describe 3 cases and attempted to determine the incidence of RTX-induced hypogammaglobulinemia by a systematic review of the literature. Methods We retrospectively analyzed 189 ITP patients receiving RTX in 3 referral centers in France and conducted a systematic review of 32 studies (results published 2001–2014) reporting the use of RTX for ITP, particularly searching for symptomatic secondary hypogammaglobulinemia. We also searched for case reports of hypogammaglobulinemia after RTX initiation for ITP. Results Of the 189 patients, 3 showed symptomatic hypogammaglobulinemia more than 2 years after RTX infusion (initial immunoglobulin level was normal). All 3 presented recurrent severe infections. In 2, the outcome suggested common variable immunodeficiency. In patient 3, the peripheral blood lacked CD19 + CD20 + B cells and the bone-marrow B-cell precursor level was impaired. Among 1245 ITP patients in the literature who received RTX for ITP, gammaglobulin level was monitored before and after RTX initiation for 351 (28%). For 192 (55%), dosages were available and we identified 21 patients with secondary hypogammaglobulinemia, usually not symptomatic, 14 of whom had received concomitant dexamethasone. Finally, we found 4 case reports of ITP and symptomatic hypogammaglobulinemia possibly related to RTX according to the authors. Conclusions This large analysis led us to recommend monitoring serum immunoglobulin level before and repeatedly after RTX initiation for ITP. Physicians should be aware of hypogammaglobulinemia as a rare but severe complication of RTX. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3-ANCA) are a serological hallmark of small vessel vasculitis, particularly granulomatosis with polyangiitis (GPA). To increase their sensitivity, some ELISA employ the human native PR3 combined with a recombinant protein. Their specificity in daily practice is still to be defined. Our objective was to compare the performance for GPA diagnosis of three PR3-ANCA assays in daily practice. Patients and methods: Seventy-eight consecutive patients' sera with suggestive IIF were included. All sera were tested with a routine Enzyme Linked Immuno adsorbant Assay (ELISA) employing a mixture of human native and human recombinant (hn+hr) PR3 (EUROIMMUN™) compared to two assays using immobilized purified human PR3 (QUANTA Lite® ELISA and QUANTA Flash® Chemiluminescence assay (CIA), INOVA Diagnostics). Clinical data including BVAS score were collected retrospectively. Results: Nineteen out of the 78 patients had GPA. The hn+hr PR3 ELISA had a good sensitivity (100%) but a lower specificity for the diagnosis of GPA (61.0%) than the assays using the sole native protein (hn ELISA: 81.4%, hn CIA: 69.5%). False positive results mainly consisted of patients with inflammatory bowel disease, who had a specific PR3-ANCA positivity assembly when coupling the assays. The antibody titers by human native PR3 assays, but not hn+hr assay, positively correlated with BVAS score. Conclusion: These results highlight the need of a close collaboration between physicians and immunologists. Combining assays including last generation CIA employing human native antigens should improve the performance of GPA's diagnosis. [ABSTRACT FROM AUTHOR]

L'émergence de variants portant des mutations dans des épitopes clés a fait craindre que l'évolution virale n'érode l'immunité acquise. Caractérisé la dynamique et la fonctionnalité de la réponse B mémoire naturelle et acquise après administration d'un vaccin à ARNm. Nous avons analysé, au cours du temps, 33 sujets avec un antécédent de la COVID-19 et 23 individus naïfs avant et après vaccination par ARNm. Nous avons combiné différentes approches, l'analyse transcriptomique en cellule unique, le séquençage du VH, le phénotypages cellulaire par cytométrie en flux multi-paramétriques ainsi que la mesure du pouvoir neutralisant des anticorps et leur affinité. La mémoire B anti-SARS-Cov-2 porte une empreinte d'un passage par le centre germinatif et parait stable chez la majorité des patients, et ce un an après l'infection initiale. Le rappel vaccinal mobilise les B mémoires sans entraîner de réduction de leur diversité. Chez les patients guéris, les B mémoires spécifiques du RBD montrent des preuves évidentes de sélection par affinité, un processus toujours en cours chez les individus naïfs, deux mois après leur deuxième dose. Seule une faible proportion de clones B mémoires spécifiques du domaine RBD n'a pas réussi à reconnaître le variant B.1.351. Néanmoins, de puissantes B mémoires neutralisant le B.1.351 pourraient toujours être détectés chez tous les individus naïfs et guéris de la Covid-19. En raison de sa diversité et de son affinité, le répertoire B mémoires anti la protéine RBDwt, sélectionné lors de l'infection ou la vaccination contient des clones capables de faire face à l'évolution virale. [ABSTRACT FROM AUTHOR]