Autoimmune Hemolytic Anemia Treatment Prednisone

  • Autoimmune haemolytic anaemia: rituximab
  • Hemolytic Anemia Medication: Vitamins, Corticosteroids, Iron Salts
  • Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review
  • Autoimmune haemolytic anaemia: rituximab | Guidance and guidelines | NICE
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  • Dog Dylan the "Miracle Dog" - Beating Autoimmune Hemolytic Anemia (AIHA)

    Autoimmune haemolytic anaemia: rituximab

    autoimmune hemolytic anemia treatment prednisone Until now, treatment of primary autoimmune hemolytic anemia of the autoimmune hemolytic anemia treatment prednisone type wAIHA is primarily based on immunosuppression. Unfortunately, the newly used therapeutic monoclonal antibodies are unspecific and remain frequently ineffective. Thus, development autoim,une a specific therapy for AIHA is necessary. Blood transfusion is the most rapidly effective measure for patients who develop or may develop hypoxic anemia. Although some effort has been made to guide physicians on how to adequately treat patients with AIHA, a number of individual aspects should be sustanon 250 and test 400 cycle autoimmune hemolytic anemia treatment prednisone to treatment. Based on my serological and clinical experience and the analysis of evidence-based studies, we remain far from any optimized therapeutic measures for all AIHA patients. Today, the old standard therapy using controlled steroid administration, with or without azathioprine or cyclophosphamide, is, when complemented with erythropoiesis-stimulating agents, still the most effective therapy in wAIHA.

    Hemolytic Anemia Medication: Vitamins, Corticosteroids, Iron Salts

    autoimmune hemolytic anemia treatment prednisone

    To receive news and publication updates for Journal of Immunology Research, enter your email address in the box below. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Warm autoimmune hemolytic anemia WAIHA is one of four clinical types of autoimmune hemolytic anemia AIHA , with the characteristics of autoantibodies maximally active at body temperature.

    It produces a variable anemia—sometimes mild and sometimes severe. With respect to the absence or presence of an underlying condition, WAIHA is either idiopathic primary or secondary, which determines the treatment strategies in practice. Conventional treatments include immune suppression with corticosteroids and, in some cases, splenectomy.

    In recent years, the number of clinical studies with monoclonal antibodies and immunosuppressants in the treatment of WAIHA increased as the knowledge of autoimmunity mechanisms extended. Following this success, other treatment methods based on the immune mechanisms of WAIHA have emerged.

    We reviewed these newly developed immunotherapy treatments here in order to provide the clinicians with more options in selecting the best therapy for patients with WAIHA, hoping to stimulate researchers to find more novel immunotherapy strategies. It can be classified by the presence or absence of pathophysiologically or etiologically associated underlying diseases. When the WAIHA appears to be a manifestation or complication of an underlying disorder, it is termed secondary. The secondary conditions may be primary immunodeficiencies such as common variable immunodeficiency, hematologic malignancies, infections, tumors, or drugs [ 3 ].

    Autoimmune diseases, particularly systemic lupus erythematosus SLE , account for a considerable proportion of the remaining secondary WAIHA cases [ 1 ]. The diagnosis of this rare disease is usually made on the laboratory findings, mainly on the direct antiglobulin test DAT. Clinicians should carefully make the treatment decisions based on the diagnostic information and should know what type of the antibody is involved and if the disease is primary or secondary [ 4 ].

    Treatments are variable by the different pathologic conditions accordingly. Recently, advances in elucidating the mechanisms of autoimmunity have been made. Attributing to this newly extended knowledge of autoimmunity, novel approaches to treating autoimmune diseases are also being worked out.

    For patients with WAIHA, current recommended therapeutic strategies include glucocorticoids as the first-line treatment and splenectomy for patients who do not show a satisfactory response to glucocorticoids. Intravenous immunoglobulin and alemtuzumab, as well as other immunosuppressive drugs, have also been successfully used in patients with WAIHA refractory to glucocorticoids and splenectomy [ 7 ].

    Treatments of WAIHA have been reviewed by several investigators [ 8 — 11 ], but none of them focused on the immunotherapy of this uncommon, severe, sometimes life-threatening disease. It is classified as activation immunotherapy if designed to elicit or amplify an immune response and classified as suppression immunotherapy if the immunotherapy reduces or suppresses the immune response.

    In consideration of the emphasis of immunotherapy of autoimmunity-related WAIHA on suppressing the immune reactivity, this review centers mainly on the immunosuppression of WAIHA through the recent advances in immunotherapy. Immunosuppressants dampen the immune response or restore balance among immune system components.

    They are primarily used to prevent or treat disease flares in autoimmune diseases and to prevent allograft rejection after organ transplantation. As an uncommon autoimmune disease, the mainstay of therapy of WAIHA is immunosuppression with corticosteroids. For patients who do not respond to corticosteroids, other immunosuppressants, including cyclosporin and azathioprine can then be used [ 15 ]. An example of application of cyclosporin is documented by Pogglitsch et al. They successfully treated a year-old patient suffering from an idiopathic warm autoimmune hemolytic anemia by cyclosporin A after the therapy of prednisone.

    The above data indicate that the immunotherapy of WAIHA with immunosuppressants has always been used and will be continued in clinics before better treatments emerge. Especially for first-line therapy, steroids will remain the preferred treatment. However, most of the immunosuppressive agents that have been tried in WAIHA patients often cause various side effects, sometimes induce refractoriness to the treatment, or lead to a relapse condition.

    Recently, this is getting closer to success as knowledge of WAIHA is rapidly increasing, especially on pathogenesis, associated disorders, and aspects of transfusion immunology. Rituximab is a humanized monoclonal antibody directed against CD20 on pre-B cells and mature B lymphocytes. Binding of rituximab to CDpositive cells results in cell death via a combination of antibody-dependent cell cytotoxicity, complement activation, and apoptosis [ 18 , 19 ].

    Due to these properties, it has been used to deplete B lymphocytes and reduce autoantibody production in the treatment of autoimmune disorders mediated by autoantibodies including the treatment of relapsed or refractory warm autoimmune hemolytic anemia patients. Eight patients achieved a complete response CR , and 3 of them achieved a partial response PR , but 6 patients still had discrete laboratory signs of hemolysis. All patients remained in either CR or PR, at a mean follow-up of days.

    The longest disease-remission duration was days. Five additional retrospective studies in mixed population of refractory primary or secondary AIHA tested the efficacy and toxicity of rituximab [ 23 — 27 ].

    About the side effects from the treatment, only one of the studies [ 23 ] showed 2 patients with severe infections and 1 patient with a myocardial infarction. The most severe potential long-term complication of rituximab treatment was reported by Carson et al.

    Most recently, Barcellini et al. The treatment was well tolerated with no adverse events or infections; retreatment was also effective. Since the main cause in SLE is the loss of B lymphocytes tolerance, targeting B lymphocytes with rituximab against the B-cell-specific calcium channel CD20 to deplete B cells from the body and lower the circulating autoantibody levels would be an effective method. Mild infusion reaction including hypotension and fever is the most common complication of rituximab, and incidence of serious infection is very low [ 36 ].

    As the evidence of rituximab treatments increases, this issue might be solved in the near future. After then, for WAIHA patients whether primary or secondary, rituximab could be considered as the first choice, thus offering a way to obtain remissions without the toxicities associated with corticosteroids and other immunosuppressive agents.

    Monoclonal antibody represents a major advance toward a targeted therapy that can dramatically improve the treatment effect with a substantial reduction of toxicity derived from therapy.

    In addition to the successful use of rituximab in WAIHA, Robak reported a second-generation, fully human, anti-CD20 monoclonal antibody with enhanced Fc effector function based on an IgG1 kappa immunoglobulin framework [ 37 ]. This newer antibody interacts with a different epitope from rituximab, which is located in the smaller extracellular loop of CD20 [ 38 ], giving it a higher binding affinity. Due to these improved properties, it received accelerated approval from the U. FDA in October and was granted a conditional marketing authorization by the European Medicines Agency in April for the treatment of patients with chronic lymphocytic leukemia CLL refractory to fludarabine and alemtuzumab [ 39 ].

    As the clinical trial data are accumulating, its wide use in clinics will be in the range soon. Alemtuzumab is a fully humanized IgG1-type mAb directed against CD52 expressed on human B and T cells, natural killer cells, eosinophils, and macrophages [ 42 , 43 ].

    Clinically, the antibody reduces normal lymphocytes of both B and T lineages, resulting in a profound and occasionally long-lasting lymphopenia with concomitant immunosuppression. The first use of this mAb in treating autoimmune hemolytic anemia was reported by Willis et al. They treated two patients with AIHA: Recent documentations on successful use of this mAb are from Karlsson et al.

    In Karlsson et al. Later on, Laurenti et al. According to the reported data [ 50 ], conventional therapies for WAIHA, such as corticosteroids, splenectomy, and immunosuppressive agents, may not induce complete resolution in all patients, and relapses are common.

    The etiology underlying the pathogenesis of such autoantibodies is still unclear. Possible mechanisms that produce a breakdown of immunologic tolerance leading to WAIHA include the possible roles of RBC autoantigens and the complement systems, the lack of effective presentation of autoantigens, functional abnormalities of B and T cells resulting in polyclonal lymphocyte activation and alteration of cytokine production, and the role of immunoregulatory T cells [ 7 ].

    For a secondary WAIHA, underlying causes may be associated with systemic lupus erythematosus, malignant tumors, benign ovarian teratomas, lymphoproliferative disorders such as chronic lymphocytic leukemia and non-Hodgkin lymphomas, or drugs. Understanding these mechanisms is vital for developing antigen-specific immunotherapies to treat the disease.

    Autoimmune hemolytic anemia AIHA has no known predisposition. There is no familial hereditary component, no age preselection, and no identified genetic background making an individual susceptible to develop AIHA [ 51 ]. Direct antiglobulin test DAT through cytofluorometry and specific diagnostic monoclonal antibodies mAbs allow for a better understanding of AIHA triggers.

    Genotyping blood groups and narrowing down the blood type subspecificities with diagnostic mAbs help to define the triggering autoantigens. In this case, authors detected the warm reactive IgM antibodies on the surface of red blood cells by cytofluorometry for the first time. Since then, the pathophysiology of IgM in human autoimmune disease has attracted much attention, which thus led to a study focus on the immunoglobulin isotypes in autoimmune hemolytic anemia.

    Such studies have not only guided the paradigm for treatment, but also extended the knowledge of the role of this molecule in the induction of AIHA [ 53 ]. Although considerable work is needed to delineate the exact role of IgM in warm AIHA and to explore its role as a key modulator of autoaggressive responses, the paradigm for treatment with immunotherapy approaches has formed on the basis of IgM pathophysiology.

    Studies of animal models and human AIHA demonstrate that the activation of autoreactive helper T Th cells by antigen presenting cells APCs is a key event in the induction of disease [ 54 ]. With synthetic peptides that are recognized by Th cells, the effector Th response can be suppressed [ 56 ]. Rhesus Rh proteins, the dominant human RBC autoantigens [ 57 , 58 ], have also been shown to be able to activate Th cells specific for epitopes on Rh proteins in the patients with primary warm type AIHA [ 59 ].

    The evidence presented by Hall et al. Blocking the activity of the Th17 pathway may be a complementary or more effective treatment strategy than inhibiting Th1 responses. Alternatively, there are possibilities of reinducing tolerance to the specific autoantigenic peptides that drive pathogenic Th-cell responses. Epitopes capable of inducing Th17 cytokine can be included as targets in this type of immunotherapies for AIHA.

    Attributing to insights into these pathogenic mechanisms, more and more new treatments have emerged, especially through monoclonal antibodies directing against certain B- or T-cell type.

    A fully human CD32 mAb has recently entered into the preclinical study for treating immune hemolytic anemia [ 62 ]. Although the evidence on the clinical use of these newly developed strategies in treating WAIHA is still in paucity, increasing survival rates and decreasing levels of life-threatening infections in patients revealed great prospects of immunotherapy for WAIHA [ 63 ].

    The first choice of treating WAIHA is steroids; however, a proportion of patients will not respond well to steroids. Although two-thirds of them respond to this treatment, they usually require maintenance therapy or even become refractory to drugs due to long-term therapy [ 64 ]. Alternative options include splenectomy and immunosuppressors. For the severe anemia and the patient for whom none of the known drugs have worked, the treatment of last resort might turn to the high dose of immunosuppressive drugs and stem-cell transplantation.

    Unfortunately, the results of these methods were disappointing and produce strongly harmful side effects [ 65 ]. Owing to the dramatic changes in the therapeutic regimens employed in autoimmune disease over the past few years, the situation is improving. With soluble receptors, monoclonal antibodies, and molecular mimetics enhancing or gradually replacing conventional immunosuppressive therapies, new immunotherapy treatments targeting defined pathways of the formation of WAIHA have become more efficacious and less toxic.

    Established data have demonstrated that rituximab is efficacious and effective in treatments of WAIHA [ 22 — 28 ]. Paying more attention to antigens on red blood cells targeted by autoantibodies would be an important factor to develop novel therapeutic mAbs.

    Exploring monoclonal antibodies against disease-related cytokines, such as IL, IL, and IL, can also be promising. Significant challenges in developing novel strategies of immunotherapy for WAIHA patients remain in the identification of optimal cellular targets, antibody forms, and treatment schedules for therapeutic applications. The authors thank Dr. Xu Lin for proofreading of the paper and valuable suggestions. This work was funded by the seed grant from Zunyi Medical College for newly recruited talents to Dr.

    Bainan Liu, and there is no any financial conflict with any entity involved in this work.

    Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

    autoimmune hemolytic anemia treatment prednisone

    Autoimmune haemolytic anaemia: rituximab | Guidance and guidelines | NICE

    autoimmune hemolytic anemia treatment prednisone

    Page not available

    autoimmune hemolytic anemia treatment prednisone