The CARMEN-France registry of adult patients with immune thrombocytopenia and autoimmune hemolytic anemia in France.

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.

[Adult immune thrombocytopenia and thrombopoietin receptor agonist: Ten years later]. / Agonistes du récepteur de la thrombopoïétine et purpura thrombopénique immunologique de l'adulte : où en sommes-nous 10 ans après ?

Ten years after their licence in France, the use of the two thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has deeply modified the landscape of immune thrombocytopenia (ITP) treatment. In this review, we summarise data on efficacy and safety of these treatments during ITP, as well as their use in clinical practice. Their place in therapeutic strategy, the recent description of persistant remission after discontinuation of TPO-RA, and future new thrombopoietic agents are also discussed. Their use has progressively increased and early use at a newly diagnosed stage of the disease is under evaluation. However physician have to keep in mind that thromboembolism rates appear to be higher with TPO-RA treatment in ITP patients at high risk of thrombosis, and that data from "real-life" studies with very long term follow up are not available. Finally, the cost of these treatments should also be evaluated in future therapeutic strategies comparisons.

[Challenges and potential solutions in first-line treatments for immune thrombocytopenia in adults]. / Traitements de première ligne au cours du purpura thrombopénique immunologique de l'adulte : état des lieux et perspectives.

The first line treatment of immune thrombocytopenic purpura (ITP) is well established and based on short course of corticosteroids associated with intravenous immunoglobulins (IVIg) for the most severe forms. Predniso(lo)ne is the corticosteroid agent usually given but dexamethasone appears as an alternative. Some guidelines recommend to use dexamethasone as first line when a rapid increase of platelet count is required. Dexamethasone could be used rather than IVIg for moderate to severe but non life-threatening bleeding manifestations. Other therapeutic options such as anti FcRn monoclonal antibodies or recombinant FcγR currently in development for ITP could be an option in the future. In newly diagnosed ITP, we unfortunately lack robust predictive risk factors of severity and chronic outcome. Identifying such factors could be helpful for considering the early use of some treatments which are commonly used as second or third line.

Rituximab and immune thrombocytopenia in adults: The state of knowledge 20 years later.

Rituximab has been used for immune thrombocytopenia (ITP) for almost 20 years and is now considered a valid off-label second-line treatment. About 60% to 70% of patients with ITP show initial response to rituximab, but in half of these patients, the disease will eventually relapse. Therefore, in 30% of patients with persistent or chronic ITP, one course of rituximab at 375 mg/m2/week for 4 weeks or 2 fixed 1000-mg rituximab infusions allows for a sustained response rate at 5 years. Unfortunately, to date, no robust predictor of long-term sustained response has been found to assist the physician in deciding to treat with rituximab on an individual basis, and the choice of rituximab or another second-line treatment must be individualized and shared with the patient. Retreatment with rituximab has been found efficient, with a similar or higher magnitude and duration of response in most patients. Rituximab is usually well tolerated, with mainly mild and easily manageable infusion-related adverse events. Severe infections are uncommon, including in the long-term, and occur in patients with at least another contributing factor in more than two thirds. Several issues remain to be resolved. Indeed, head-to-head comparisons with other and new treatments in ITP and robust predictors of long-term response are urgently needed to better determine the position of rituximab in the therapeutic armamentarium for adult ITP. Additionally, the place of combination therapies, maintenance therapy with rituximab and rituximab in newly-diagnosed ITP deserve additional studies.

[Expectation of patients and caregivers about patient education for immune thrombocytopenia]. / Attentes en éducation thérapeutique des patients atteints de purpura thrombopénique immunologique et des soignants.

INTRODUCTION: Immune thrombocytopenia (ITP) durably affects quality of life in patients. Patient education aims at improving their self-care and psychosocial skills, allowing them be more autonomous, to prevent avoidable complications, and to maintain or improve quality of life. The aim of this study was to assess patients' and caregivers' expectations regarding patient education in ITP. METHOD: ITP Patients and caregivers were asked about topics that should be addressed in a patient education program through a digital anonymous survey. Their responses were analyzed both qualitatively and quantitatively. A double-blind keyword attribution of the answers was carried out by two physicians and then faced until consensus was found. RESULTS: Thirty-eight ITP patients were included: 68% were less than 50 years old and 84% had chronic ITP. On the other hand, twenty-five caregivers were included. Caregivers raised more topics related to the cognitive domain than patients. The psychoaffective and motivational topics tended to be more represented in patients' responses. Only 53% of topics were mentioned by both patients and caregivers. CONCLUSION: These discrepancies emphasize the differences between patients and caregivers' expectations regarding a patient education program in ITP, and thus the relevance of patient-caregiver co-construction of such programs.

[Secondary ITP in adults]. / Les purpuras thrombopéniques immunologiques secondaires de l'adulte.

Secondary forms of immune thrombocytopenia (ITP) represent approximately 20% of all ITP cases in adulthood and this rate increases with age. Since some causes may influence both the prognosis and outcome but also the management of ITP, a minimal workup must be performed at ITP diagnosis to look for an associated or underlying cause. Among adults, B-cell lymphomas and mainly chronic lymphocytic leukemia, systemic auto-immune diseases such as systemic lupus or primary immunodeficiencies mainly represented by common variable immunodeficiency are the most frequent causes of secondary ITP. Whereas first-line therapy used for secondary ITP is usually similar to the one commonly used in primary ITP and relies mostly on corticosteroids±intravenous immunoglobulin according to the severity of bleeding, second and third-line treatments must take into account the type and degree of activity of the underlying disease.

[Immune thrombocytopenia: From pathogenesis to treatment]. / Thrombopénie immunologique : de la physiopathologie aux traitements.

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an immune peripheral destruction of platelets and an inappropriate platelet production. The pathogenesis of ITP is now better understood: it involves a humoral immune response which dependents on the stimulation of B cells by specific T cells called T follicular helper cells, leading to their differentiation into plasma cells that produce antiplatelet antibodies thus promoting the phagocytosis of platelets mainly by splenic macrophages. The deciphering of ITP pathogenesis has led to a better understanding of the inefficiency of treatments such as rituximab, although it has not provided yet the determination of biological predictive factor of response to treatments. Moreover, new therapeutic perspectives have been opened in the last few years with the development of molecules targeting Fcγ receptor signalling such as Syk inhibitor, or molecules increasing the clearance of pathogenic autoantibodies such as inhibitors of the neonatal Fc receptor (FcRn).

[Diagnostic performance of κ/λ serum free light chain ratio (Freelite® assay) and IgGκ/IgGλ ratio (Hevylite® assay) as prognostic biomarkers of the evolution of immune thrombocytopenia into a chronic disease in adult patients]. / Performance diagnostique des rapports κ/λ des chaines légères libres sériques (test Freelite®) et IgGκ/IgGλ (test Hevylite®) comme marqueurs pronostiques de chronicisation du purpura thrombopénique immunologique de l'adulte.

INTRODUCTION: Immune thrombocytopenia (ITP) is an acquired hemorrhagic disease due to antiplatelet antibodies, that will become a chronic disease in 70% of adults. Most of chronic ITP patients display clonal restriction of antiplatelet antibodies. To date, there is no biomarker able to predict the evolution of the disease. The objective of the study is to determine whether Hevylite® and/or Freelite® assays are prognostic factors for progression to chronic ITP. METHODS: This is a retrospective, monocentric, prognostic study of a biomarker, performed using frozen samples stored in a serum library. Freelite® and a Hevylite® assays were performed on the samples collected at diagnosis for adult patients with newly diagnosed ITP at the University Hospital of Poitiers between 2014/01/01 and 2017/05/01. To predict the evolution into a chronic disease, a ROC curve analysis was performed on four variables: IgGκ, IgGκ/IgGλ ratio, IgGκ - IgGλ, and κ/λ ratio. RESULTS: Thirty-two patients were included and analyzed. No patient had an abnormal κ/λ ratio. Three patients had an abnormal IgGκ/IgGλ ratio. The following variables IgGκ, IgGκ/IgGλ, IgGκ - IgGλ, and κ/λ ratio were not able to predict progression to chronic ITP in our study. CONCLUSION: This study did not reveal any prognostic value of the Freelite® and Hevylite® tests on the evolution of ITP into a chronic disease.

[Autoimmune hemolytic anemia and immune thrombocytopenia associated with Hodgkin disease: Retrospective monocentric study]. / Cytopénies auto-immunes associées au lymphome de Hodgkin : étude rétrospective monocentrique.

INTRODUCTION: Hodgkin's lymphoma (HL) is less common than non-Hodgkin lymphoma and is rarely associated with autoimmune cytopenia. METHOD: We report a consecutive, monocentric and retrospective series of HL patients diagnosed with concomitant or subsequent autoimmune cytopenia over a period of 8 years. RESULTS: We report 4 out of 84 HL patients (4.8%) diagnosed with autoimmune cytopenia (4 immune thrombocytopenia including 2 Evans' syndromes). They were 4 males (average age 24 years for the 3 youngest, and one over 60 years old). Autoimmune cytopenia revealed lymphoma in 2 patients and occurred after HL treatment in the two other patients (5 and 36 months from the end of chemotherapy) without HL relapse. All cytopenias were resistant to conventional treatments (glucocorticoids, intravenous immune globulin, rituximab) and sensitive to chemotherapy when indicated for HL treatment. CONCLUSION: In our series, the predominance of males, a higher frequency of immune thrombocytopenia than autoimmune hemolytic anemia, the resistance to usual treatments and the efficacy of specific chemotherapy were consistent with the literature. Unexpectedly, patients were young and with nodular sclerosis morphology (vs. mixed cellularity) in 3 of 4 cases.

[Immune thrombocytopenia and pregnancy: State of knowledge and unanswered questions]. / Purpura thrombopénique immunologique et grossesse : état des connaissances actuelles et questions encore sans réponse.

Pregnancy is a common problem in women with immune thrombocytopenia (ITP). It could be a source of anxiety for the patients and their family, nurses and medical doctors and many questions are unresolved in this setting. Most of published recommendations were based on experts' opinion rather than on evidence-based medicine and randomized studies. The objectives of this article are to remind the known recommendations and to discuss the unresolved questions and the prospective.

[Antenatal management for patients with increased risk of post-partum hemorrhage (excluding abnormal placentation)]. / Prise en charge anténatale des patientes à risque d'hémorragie du post-partum (hors anomalies de l'insertion placentaire).

OBJECTIVES: To describe management and screening for high-risk patients concerning post-partum hemorrhage (PPH) and antenatal management for severe anemia, thrombopenia, bleeding disorders and anticoagulant therapy. METHODS: Bibliographic search restricted to French and English languages using Medline database and recommendations of medical societies. RESULTS: The appropriate place for delivery should be chosen after multidisciplinary concertation based on level of risk (especially past-history of severe PPH and bleeding disorder) and easy access to blood products (Professional Consensus). Prevention for severe anemia is mainly based on oral iron supplementation (grade B). Explorations are required in case of thrombopenia<100Giga/L (grade C). Patients with bleeding disorder require the assistance of a physician skilled in hemostasis for perinatal management (grade C). Preventive anticoagulant therapy has no impact on PPH risk and perimedullar analgesia is usually authorized 12hours after last injection (grade C). Curative anticoagulant therapy slightly increases PPH risk and perimedullar analgesia is authorized only after 24hours since last injection (Professional Consensus). CONCLUSION: Prenatal identification of high-risk patients concerning PPH implies multidisciplinary concertation to determine the most appropriate birthplace where technical and human resources are available.

[Post-splenectomy complications in primary immune thrombocytopenia. Literature review and preventive measures]. / Complications de la splénectomie au cours du purpura thrombopénique immunologique. Revue de la littérature et mesures de prévention.

Management of primary immune thrombocytopenia (ITP) has changed, and clinical practice broadens the use of thrombopoietin receptor agonists and anti-CD20 antibody as options for second-line therapy, as alternative to splenectomy. Splenectomy remains a successful, definitive curative treatment. The purpose of this review about the complications of the splenectomy, in the context of ITP, is to increase the awareness of clinicians towards the preventive measures, which are often not correctly applied.