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Blood Jun 2021
Topics: Anemia, Hemolytic, Autoimmune; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Thrombocytopenia
PubMed: 34165542
DOI: 10.1182/blood.2021010944 -
La Tunisie Medicale Jan 2024Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune...
Autoimmune cytopenias are defined by autoantibodies' immune destruction of one or more blood elements. Most often it is autoimmune hemolytic anemia or immune thrombocytopenia or both that define Evans syndrome. It may be secondary to infection or to underlying pathology such as systemic autoimmune disease or primary immunodeficiency, especially when it becomes chronic over several years. Primary Immunodeficiencies or inborn errors of immunity (IEI) are no longer defined solely by infections: autoimmunity is part of the clinical features of several of these diseases. It is dominated by autoimmune cytopenias, in particular, immune thrombocytopenia (ITP) and autoimmune hemolytic anaemia (AIHA). The challenges for the clinician are the situations where autoimmune cytopenias are chronic, recurrent and/or refractory to the various long-term therapeutic options. Most of these therapies are similar in action and generally consist of non-mediated immune suppression or modulation. In these situations, primary Immunodeficiencies must be diagnosed as soon as possible to allow the initiation of a targeted treatment and to avoid several ineffective therapeutic lines.
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Cytopenia; Anemia, Hemolytic, Autoimmune; Thrombocytopenia
PubMed: 38545722
DOI: 10.62438/tunismed.v102i1.4503 -
American Journal of Hematology Jan 2020
Review
Topics: Anemia, Hemolytic, Autoimmune; Humans; Immunoglobulin A
PubMed: 31328297
DOI: 10.1002/ajh.25581 -
British Journal of Haematology Apr 2017
Topics: Humans; Anemia, Hemolytic, Autoimmune; Disease Management
PubMed: 28369704
DOI: 10.1111/bjh.14654 -
Blood Reviews Jul 2017The complement system is an essential part of the innate immune system that requires careful regulation to ensure responses are appropriately directed against harmful... (Review)
Review
The complement system is an essential part of the innate immune system that requires careful regulation to ensure responses are appropriately directed against harmful pathogens, while preventing collateral damage to normal host cells and tissues. While deficiency in some components of the complement pathway is associated with increased susceptibility to certain infections, it has also become clear that inappropriate activation of complement is an important contributor to human disease. A number of hematologic disorders are driven by complement, and these disorders may be termed "complementopathies". This includes paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), cold agglutinin disease (CAD) and other related disorders, which will be the focus of this review. A better understanding of the central role of the complement system in the pathophysiology of these disorders may allow for application of therapies directed at blocking the complement cascade.
Topics: Adaptive Immunity; Anemia, Hemolytic, Autoimmune; Animals; Atypical Hemolytic Uremic Syndrome; Complement Activation; Complement System Proteins; Female; HELLP Syndrome; Hemoglobinuria, Paroxysmal; Humans; Immunity, Innate; Pregnancy
PubMed: 28215731
DOI: 10.1016/j.blre.2017.02.003 -
American Journal of Hematology Jan 2017This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly... (Randomized Controlled Trial)
Randomized Controlled Trial
This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre-defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2-week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with 11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P = 0.011). Overall, eight severe infections occurred during follow-up, six with placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly-diagnosed wAIHA in adults. Am. J. Hematol. 92:23-27, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Aged; Anemia, Hemolytic, Autoimmune; Disease-Free Survival; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Immunologic Factors; Male; Prednisolone; Prospective Studies; Rituximab; Treatment Outcome
PubMed: 27696475
DOI: 10.1002/ajh.24570 -
Current Opinion in Hematology Nov 2023Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this... (Review)
Review
PURPOSE OF REVIEW
Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this condition, some of the unusual and more recent findings have not been fully defined and may be contentious. This review will provide insight into the common specificity of the warm autoantibodies and hypothesize a novel mechanism of wAIHA, that is proposed to be linked to the controversial subject of red blood cell senescence.
RECENT FINDINGS AND HYPOTHESES
It is now well established that band 3 on the red blood cell is the main target of autoantibodies in wAIHA. wAIHA targets the older red blood cells (RBCs) in about 80% of cases and, recently, it has been shown that the RBCs in these patients are aging faster than normal. It has been proposed that in these 80% of patients, that the autoantibody recognizes the senescent red blood cell antigen on band 3. It is further hypothesized that this autoantibody's production and potency has been exacerbated by hypersensitization to the RBC senescent antigen, which is processed through the adaptive immune system to create the pathogenic autoantibody. Recent publications have supported previous data that the senescent RBC antigen is exposed via a dynamic process, wherein oscillation of a band 3 internal loop flipping to the cell surface, creates a conformational neoantigen that is the RBC senescent antigen. It has also recently been shown that the cytokine profile in patients with wAIHA favors production of inflammatory cytokines/chemokines that includes interleukin-8 which can activate neutrophils to increase the oxidative stress on circulating RBCs to induce novel antigens, as has been postulated to favour exposure of the senescent RBC antigen.
SUMMARY
This manuscript reviews new findings and hypotheses regarding wAIHA and proposes a novel mechanism active in most wAIHA patients that is due to an exacerbation of normal RBC senescence.
Topics: Humans; Anemia, Hemolytic, Autoimmune; Immunoglobulin G; Erythrocytes; Autoantibodies
PubMed: 37497853
DOI: 10.1097/MOH.0000000000000779 -
Hematology/oncology and Stem Cell... Dec 2020
Topics: Anemia, Hemolytic, Autoimmune; Bortezomib; Humans; Purpura, Thrombocytopenic, Idiopathic
PubMed: 31202670
DOI: 10.1016/j.hemonc.2019.05.006 -
Blood Jul 2020We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to... (Clinical Trial)
Clinical Trial Observational Study
We retrospectively studied 232 patients with cold agglutinin disease (CAD) at 24 centers in 5 countries. In Norway and a northern region of Italy, the study was close to being population-based. For the first time, we demonstrate fourfold differences between cold and warmer climates regarding prevalence (20 vs 5 cases/million) and incidence (1.9 vs 0.48 cases/million per year). Mean baseline hemoglobin level was 9.3 g/dL, but 27% had hemoglobin <8 g/dL. Identification of typical features of CAD-associated lymphoproliferative disorder in the bone marrow was greatly increased by centralized biopsy assessment. CAD seems to be associated with a slightly increased risk of venous thrombosis. This work includes a follow-up study of therapies, focusing on the long-term outcomes of the rituximab plus bendamustine and rituximab plus fludarabine regimens. Rituximab plus bendamustine therapy resulted in responses in 35 (78%) of 45 patients; 24 (53%) achieved complete response. Interestingly, these rates were still higher than observed in the original (2017) prospective trial, and we also found a shift toward deeper responses with time. This is explained by the prolonged time to response seen in many patients, probably related to long-lived plasma cells. In patients responding to rituximab-bendamustine, median response duration was not reached after 88 months, and estimated 5-year sustained remission was 77%. The regimen appeared safe regarding late-occurring malignancies. Rituximab plus fludarabine therapy seems to carry a higher risk of long-term adverse effects.
Topics: Adult; Aged; Anemia, Hemolytic, Autoimmune; Bendamustine Hydrochloride; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Retrospective Studies; Rituximab; Vidarabine
PubMed: 32374875
DOI: 10.1182/blood.2020005674 -
Hematology. American Society of... Dec 2016Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie,... (Review)
Review
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders. This review will focus on the postulated immunopathogenetic mechanisms in idiopathic and secondary w-AIHA and report on the rare cases of direct antiglobulin test-negative AIHA, which are even more likely to be fatal because of inherent characteristics of the causative antibodies, as well as because of delays in diagnosis and initiation of appropriate treatment. Then, the characteristics of w-AIHA associated with genetically defined immune dysregulation disorders and special considerations on its management will be discussed. Finally, the standard treatment options and newer therapeutic approaches for this chronic autoimmune blood disorder will be reviewed.
Topics: Adult; Anemia, Hemolytic, Autoimmune; Female; Humans; Male
PubMed: 27913548
DOI: 10.1182/asheducation-2016.1.690