The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Bruno Fattizzo - One of the best experts on this subject based on the ideXlab platform.
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Autoimmune Hemolytic Anemia in adults primary risk factors and diagnostic procedures
Expert Review of Hematology, 2020Co-Authors: Wilma Barcellini, Bruno Fattizzo, Juri Alessandro GiannottaAbstract:Autoimmune Hemolytic Anemia (AIHA) is due to autoantibodies against erythrocytes that may arise either because of primary tolerance breakage or along with several associated conditions, including g...
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Autoimmune Hemolytic Anemia Autoimmune neutropenia and aplastic Anemia in the elderly
European Journal of Internal Medicine, 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Agostino CortelezziAbstract:The physiology of the immune system involves morphologic and functional changes occurring along ageing, with a decrease in immune response and an increase in Autoimmune phenomena, even in the absence of overt disese. Autoimmune cytopenias, namely Autoimmune Hemolytic Anemia (AIHA), chronic idiopathic neutropenia (CIN) and aplastic Anemia (AA), show different epidemiologic predilection, but are increasingly diagnosed in the elderly, where complications and comorbidities are more frequent. A systematic review of recent literature, shows that comorbidities as well as underlying deficiencies, medications, neoplasms, and, pathophysiologic chronic organ failures, frequently challenge the differential diagnosis in this setting and should always be evaluated and excluded. Complications, particularly infections and thrombosis for AIHA, and bleeding for AA, should be monitored and promptly treated. Treatment choice should be carefully weighed on the individual general condition and comorbidities, granted that intense primary care and support (including evidence-based transfusion policies) are provided. Finally, bone marrow histology is highly advisable in the elderly, both at diagnosis to detect underlying conditions, and along the follow-up to monitor possible bone marrow failure or neoplastic evolution.
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current and emerging treatment options for Autoimmune Hemolytic Anemia
Expert Review of Clinical Immunology, 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Anna ZaninoniAbstract:Introduction: Autoimmune Hemolytic Anemia (AIHA) is a heterogeneous disease mainly due to autoantibody-mediated destruction of erythrocytes but also involves complement activation, dysregulation of...
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Current and emerging treatment options for Autoimmune Hemolytic Anemia
'Informa UK Limited', 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Anna ZaninoniAbstract:Introduction: Autoimmune Hemolytic Anemia (AIHA) is a heterogeneous disease mainly due to autoantibody-mediated destruction of erythrocytes but also involves complement activation, dysregulation of cellular and innate immunity, and defective bone marrow compensatory response. Several drugs targeting these mechanisms are under development in addition to standard therapies. Areas covered: The following targeted therapies are illustrated: drugs acting on CD20 (rituximab, alone or in association with bendamustine and fludarabine) and CD52 (alemtuzumab), B cell receptor and proteasome inhibitors (ibrutinib, bortezomib), complement inhibitors (eculizumab, BIVV009, APL-2), and other drugs targeting T lymphocytes (subcutaneous IL-2, belimumab, and mTOR inhibitors), IgG driven extravascular hemolysis (fostamatinib), and bone marrow activity (luspatercept). Expert opinion: Although AIHA is considered benign and often easy to treat, chronic/refractory cases represent a challenge even for experts in the field. Bone marrow biopsy is fundamental to assess one of the main mechanisms contributing to AIHA severity, i.e. inadequate compensation, along with lymphoid infiltrate, the presence of fibrosis or dyserythropoiesis. The latter may give hints for targeted therapies (either B or T cell directed) and for new immunomodulatory drugs. Future studies on the genomic landscape in AIHA will further help in designing the best choice, sequence and/or combination of targeted therapies
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low dose rituximab in adult patients with idiopathic Autoimmune Hemolytic Anemia clinical efficacy and biologic studies
Blood, 2012Co-Authors: Wilma Barcellini, Bruno Fattizzo, Agostino Cortelezzi, Anna Zaninoni, Francesco Zaja, Francesca Guia Imperiali, Marta Lisa Battista, Eros Di Bona, Dario Consonni, Renato FaninAbstract:This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary Autoimmune Hemolytic Anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm Autoimmune Hemolytic Anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.
Wilma Barcellini - One of the best experts on this subject based on the ideXlab platform.
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Autoimmune Hemolytic Anemia in adults primary risk factors and diagnostic procedures
Expert Review of Hematology, 2020Co-Authors: Wilma Barcellini, Bruno Fattizzo, Juri Alessandro GiannottaAbstract:Autoimmune Hemolytic Anemia (AIHA) is due to autoantibodies against erythrocytes that may arise either because of primary tolerance breakage or along with several associated conditions, including g...
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Autoimmune Hemolytic Anemia Autoimmune neutropenia and aplastic Anemia in the elderly
European Journal of Internal Medicine, 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Agostino CortelezziAbstract:The physiology of the immune system involves morphologic and functional changes occurring along ageing, with a decrease in immune response and an increase in Autoimmune phenomena, even in the absence of overt disese. Autoimmune cytopenias, namely Autoimmune Hemolytic Anemia (AIHA), chronic idiopathic neutropenia (CIN) and aplastic Anemia (AA), show different epidemiologic predilection, but are increasingly diagnosed in the elderly, where complications and comorbidities are more frequent. A systematic review of recent literature, shows that comorbidities as well as underlying deficiencies, medications, neoplasms, and, pathophysiologic chronic organ failures, frequently challenge the differential diagnosis in this setting and should always be evaluated and excluded. Complications, particularly infections and thrombosis for AIHA, and bleeding for AA, should be monitored and promptly treated. Treatment choice should be carefully weighed on the individual general condition and comorbidities, granted that intense primary care and support (including evidence-based transfusion policies) are provided. Finally, bone marrow histology is highly advisable in the elderly, both at diagnosis to detect underlying conditions, and along the follow-up to monitor possible bone marrow failure or neoplastic evolution.
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current and emerging treatment options for Autoimmune Hemolytic Anemia
Expert Review of Clinical Immunology, 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Anna ZaninoniAbstract:Introduction: Autoimmune Hemolytic Anemia (AIHA) is a heterogeneous disease mainly due to autoantibody-mediated destruction of erythrocytes but also involves complement activation, dysregulation of...
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Current and emerging treatment options for Autoimmune Hemolytic Anemia
'Informa UK Limited', 2018Co-Authors: Wilma Barcellini, Bruno Fattizzo, Anna ZaninoniAbstract:Introduction: Autoimmune Hemolytic Anemia (AIHA) is a heterogeneous disease mainly due to autoantibody-mediated destruction of erythrocytes but also involves complement activation, dysregulation of cellular and innate immunity, and defective bone marrow compensatory response. Several drugs targeting these mechanisms are under development in addition to standard therapies. Areas covered: The following targeted therapies are illustrated: drugs acting on CD20 (rituximab, alone or in association with bendamustine and fludarabine) and CD52 (alemtuzumab), B cell receptor and proteasome inhibitors (ibrutinib, bortezomib), complement inhibitors (eculizumab, BIVV009, APL-2), and other drugs targeting T lymphocytes (subcutaneous IL-2, belimumab, and mTOR inhibitors), IgG driven extravascular hemolysis (fostamatinib), and bone marrow activity (luspatercept). Expert opinion: Although AIHA is considered benign and often easy to treat, chronic/refractory cases represent a challenge even for experts in the field. Bone marrow biopsy is fundamental to assess one of the main mechanisms contributing to AIHA severity, i.e. inadequate compensation, along with lymphoid infiltrate, the presence of fibrosis or dyserythropoiesis. The latter may give hints for targeted therapies (either B or T cell directed) and for new immunomodulatory drugs. Future studies on the genomic landscape in AIHA will further help in designing the best choice, sequence and/or combination of targeted therapies
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new insights in the pathogenesis of Autoimmune Hemolytic Anemia
Transfusion Medicine and Hemotherapy, 2015Co-Authors: Wilma BarcelliniAbstract:Autoimmune Hemolytic Anemia (AIHA) is caused by the increased destruction of red blood cells (RBCs) by anti-RBC autoantibodies with or without complement activation. RBC destruction may occur both by a direct lysis through the sequential activation of the final components of the complement cascade (membrane attack complex), or by antibody-dependent cell-mediated cytotoxicity (ADCC). The pathogenic role of autoantibodies depends on their class (the most frequent are IgG and IgM), subclass, thermal amplitude (warm and cold forms),as well as affinity and efficiency in activating complement. Several cytokines and cytotoxic mechanisms (CD8+ T and natural killer cells) are further involved in RBC destruction. Moreover, activated macrophages carrying Fc receptors may recognize and phagocyte erythrocytes opsonized by autoantibodies and complement. Direct complement-mediated lysis takes place mainly in the circulations and liver, whereas ADCC, cytotoxicity, and phagocytosis occur preferentially in the spleen and lymphoid organs. The degree of intravascular hemolysis is 10-fold greater than extravascular one. Finally, the efficacy of the erythroblastic compensatory response can greatly influence the clinical picture of AIHA. The interplay and relative burden of all these pathogenic mechanisms give reason for the great clinical heterogeneity of AIHAs, from fully compensated to rapidly evolving fatal cases.
George B Segel - One of the best experts on this subject based on the ideXlab platform.
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direct antiglobulin coombs test negative Autoimmune Hemolytic Anemia a review
Blood Cells Molecules and Diseases, 2014Co-Authors: George B Segel, Marshall A LichtmanAbstract:Abstract We have reviewed the literature to identify and characterize reports of warm-antibody type, Autoimmune Hemolytic Anemia in which the standard direct antiglobulin reaction was negative but a confirmatory test indicated that the red cells were opsonized with antibody. Three principal reasons account for the absence of a positive direct antiglobulin test in these cases: a) IgG sensitization below the threshold of detection by the commercial antiglobulin reagent, b) low affinity IgG, removed by preparatory washes not conducted at 4 °C or at low ionic strength, and c) red cell sensitization by IgA alone, or rarely (monomeric) IgM alone, but not accompanied by complement fixation, and thus not detectable by a commercial antiglobulin reagent that contains anti-IgG and anti-C3. In cases in which the phenotype is compatible with warm-antibody type, Autoimmune Hemolytic Anemia and the direct antiglobulin test is negative, an alternative method to detect low levels of IgG sensitization, use of 4 °C, low ionic strength washes to prepare the cells for the direct antiglobulin test reaction to permit retention and identification of low affinity IgG antibodies, and, if the latter are uninformative, testing for sensitization with an anti-IgA, and, if necessary, an anti-IgM reagent identifies cases of warm-antibody type, immune hemolysis not verified by a commercial reagent.
Jeanette Lundin - One of the best experts on this subject based on the ideXlab platform.
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alemtuzumab to treat refractory Autoimmune Hemolytic Anemia or thrombocytopenia in chronic lymphocytic leukemia
Current Hematologic Malignancy Reports, 2009Co-Authors: Anders Osterborg, Claes Karlsson, Jeanette LundinAbstract:Autoimmune Hemolytic Anemia (AIHA) and immune thrombocytopenic purpura (ITP) are recognized complications of chronic lymphocytic leukemia (CLL) that can be life-threatening if not managed appropriately. Conventional therapies for these Autoimmune disorders, such as corticosteroids, splenectomy, and immunosuppressive agents, may not induce complete resolution in all patients, and relapses are common. In recent years, monoclonal antibodies such as alemtuzumab and rituximab, already used successfully for the management of lymphoproliferative disorders, have been shown to be effective in the treatment of a range of Autoimmune disorders. The potent antitumor activity of alemtuzumab, in combination with its profound immunosuppressive activity, prompted investigation of its use in patients with severe CLL-related AIHA and ITP. Results from a range of reports confirm the efficacy of alemtuzumab for the treatment of severe, CLL-related Autoimmune cytopenias that have failed to respond to conventional therapies and may even be rituximab-refractory.
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treatment of severe refractory Autoimmune Hemolytic Anemia in b cell chronic lymphocytic leukemia with alemtuzumab humanized cd52 monoclonal antibody
Leukemia, 2007Co-Authors: Claes Karlsson, Lotta Hansson, Fredrik Celsing, Jeanette LundinAbstract:Treatment of severe refractory Autoimmune Hemolytic Anemia in B-cell chronic lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody)
Marshall A Lichtman - One of the best experts on this subject based on the ideXlab platform.
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direct antiglobulin coombs test negative Autoimmune Hemolytic Anemia a review
Blood Cells Molecules and Diseases, 2014Co-Authors: George B Segel, Marshall A LichtmanAbstract:Abstract We have reviewed the literature to identify and characterize reports of warm-antibody type, Autoimmune Hemolytic Anemia in which the standard direct antiglobulin reaction was negative but a confirmatory test indicated that the red cells were opsonized with antibody. Three principal reasons account for the absence of a positive direct antiglobulin test in these cases: a) IgG sensitization below the threshold of detection by the commercial antiglobulin reagent, b) low affinity IgG, removed by preparatory washes not conducted at 4 °C or at low ionic strength, and c) red cell sensitization by IgA alone, or rarely (monomeric) IgM alone, but not accompanied by complement fixation, and thus not detectable by a commercial antiglobulin reagent that contains anti-IgG and anti-C3. In cases in which the phenotype is compatible with warm-antibody type, Autoimmune Hemolytic Anemia and the direct antiglobulin test is negative, an alternative method to detect low levels of IgG sensitization, use of 4 °C, low ionic strength washes to prepare the cells for the direct antiglobulin test reaction to permit retention and identification of low affinity IgG antibodies, and, if the latter are uninformative, testing for sensitization with an anti-IgA, and, if necessary, an anti-IgM reagent identifies cases of warm-antibody type, immune hemolysis not verified by a commercial reagent.
