Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.4
3.9
Journals
JCM
Special Issues
Diagnosis and Management of Autoimmune Hemolytic Anemias
share announcement

Diagnosis and Management of Autoimmune Hemolytic Anemias

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 71644

Special Issue Editors

Prof. Dr. Wilma Barcellini

E-Mail Website
Guest Editor
UOC Ematologia, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico, Milan, Italy
Interests: autoimmune hemolytic anemias; congenital hemolytic anemias; paroxysmal nocturnal hemoglobimuria(EPN); hematology
Dr. Bruno Fattizzo

E-Mail Website
Co-Guest Editor
IRCCS Ca Granda Ospedale Maggiore Policlinico Department Hematology, Milan, Italy
Interests: autoimmune hemolytic anemias; congenital hemolytic anemias; paroxysmal nocturnal hemoglobimuria(EPN); primary autoimmune hemolytic anemia (AIHA); hematology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Autoimmune hemolytic anemia (AIHA) is a rare and clinically heterogeneous disease ranging from mild to life-threatening hemolysis. It has been historically recognized as an autoantibody-mediated condition, where warm IgG, cold IgM, or both cause antibody-dependent intra- or extravascular hemolysis. More recently, the role of the final effectors of immune hemolysis, i.e., the complement cascade and the reticuloendothelial system, has gained attention. In addition, the importance of bone marrow compensation has emerged as a pivotal factor, and there is evidence that inadequate reticulocytosis correlates with very severe anemia and worse outcome. These observations have paved the way to novel targeted therapies in combination with current treatments based on steroids, rituximab, and splenectomy.

The clinical picture of AIHA is further complicated by the presence of several underlying conditions including infections, lymphoproliferative neoplasms, autoimmune diseases, immunodeficiencies, and tumors, whose diagnosis may either precede or follow that of AIHA. More recently, AIHA has been associated with bone marrow transplantation and with novel biologic anti-cancer drugs. Furthermore, AIHA presentation and related complications may be risk factors for disease refractoriness and mortality. The importance of assessing the presence of these conditions is crucial, since specific treatments may be required, and the risk of infectious and thrombotic complications may vary depending on the diagnosed condition.

Prof. Dr. Wilma Barcellini
Dr. Bruno Fattizzo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • primary autoimmune hemolytic anemia (AIHA)
  • AIHA secondary to lymphoproliferative neoplasms
  • AIHA secondary to other autoimmune diseases
  • AIHA secondary to immunodeficiencies
  • direct antiglobulin test
  • thrombosis
  • AIHA therapy
  • drug-associated AIHA.

Published Papers (8 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Review

9 pages, 216 KiB  
Review
The Role of Novel Agents in Treating CLL-Associated Autoimmune Hemolytic Anemia
by Alessandro Noto, Ramona Cassin, Veronica Mattiello and Gianluigi Reda
J. Clin. Med. 2021, 10(10), 2064; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10102064 - 12 May 2021
Cited by 6 | Viewed by 3106
Abstract
Autoimmune cytopenias (AICs) have been reported as a common complication in chronic lymphocytic leukemia (CLL) with autoimmune hemolytic anemia (AIHA), accounting for most cases. According to iwCLL guidelines, AICs poorly responsive to corticosteroids are considered indication for CLL-directed treatment. Chemo-immunotherapy has classically been [...] Read more.
Autoimmune cytopenias (AICs) have been reported as a common complication in chronic lymphocytic leukemia (CLL) with autoimmune hemolytic anemia (AIHA), accounting for most cases. According to iwCLL guidelines, AICs poorly responsive to corticosteroids are considered indication for CLL-directed treatment. Chemo-immunotherapy has classically been employed, with variable results, and little data are available on novel agents, the current backbone of CLL therapy. The use of idelalisib in the setting of AICs is controversial and recent recommendations suggest avoiding idelalisib in this setting. Ibrutinib, through ITK-driven Th1 polarization of cell-mediated immune response, is known to produce an immunological rebalancing in CLL, which stands as a fascinating rationale for its use to treat autoimmunity. Although treatment-emergent AIHA has rarely been reported, ibrutinib has shown rapid and durable responses when used to treat AIHA arising in CLL. There is poor evidence regarding the role of BCL-2 inhibitors in CLL-associated AICs and the use of venetoclax in such cases is debated. Furthermore, their frequent use in combination with anti-CD20 agents might represent a confounding factor in evaluating their efficacy. In conclusions, because of their ability to mitigate an immunological dysregulation that is (at least partly) responsible for autoimmunity in CLL, to date BTK-inhibitors stand out as the most suitable choice when treatment of autoimmune cytopenias is required. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
13 pages, 1790 KiB  
Review
Epidemiology of Secondary Warm Autoimmune Haemolytic Anaemia—A Systematic Review and Meta-Analysis
by Stinne Tranekær, Dennis Lund Hansen and Henrik Frederiksen
J. Clin. Med. 2021, 10(6), 1244; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10061244 - 17 Mar 2021
Cited by 10 | Viewed by 3262
Abstract
Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved [...] Read more.
Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
►▼ Show Figures

Figure 1

13 pages, 333 KiB  
Review
Diagnosis and Management of Autoimmune Hemolytic Anemia in Patients with Liver and Bowel Disorders
by Cristiana Bianco, Elena Coluccio, Daniele Prati and Luca Valenti
J. Clin. Med. 2021, 10(3), 423; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10030423 - 22 Jan 2021
Cited by 9 | Viewed by 7257
Abstract
Anemia is a common feature of liver and bowel diseases. Although the main causes of anemia in these conditions are represented by gastrointestinal bleeding and iron deficiency, autoimmune hemolytic anemia should be considered in the differential diagnosis. Due to the epidemiological association, autoimmune [...] Read more.
Anemia is a common feature of liver and bowel diseases. Although the main causes of anemia in these conditions are represented by gastrointestinal bleeding and iron deficiency, autoimmune hemolytic anemia should be considered in the differential diagnosis. Due to the epidemiological association, autoimmune hemolytic anemia should particularly be suspected in patients affected by inflammatory and autoimmune diseases, such as autoimmune or acute viral hepatitis, primary biliary cholangitis, and inflammatory bowel disease. In the presence of biochemical indices of hemolysis, the direct antiglobulin test can detect the presence of warm or cold reacting antibodies, allowing for a prompt treatment. Drug-induced, immune-mediated hemolytic anemia should be ruled out. On the other hand, the choice of treatment should consider possible adverse events related to the underlying conditions. Given the adverse impact of anemia on clinical outcomes, maintaining a high clinical suspicion to reach a prompt diagnosis is the key to establishing an adequate treatment. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
13 pages, 622 KiB  
Review
Autoimmune Hemolytic Anemia in the Pediatric Setting
by Aikaterini Voulgaridou and Theodosia A. Kalfa
J. Clin. Med. 2021, 10(2), 216; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020216 - 09 Jan 2021
Cited by 22 | Viewed by 6878
Abstract
Autoimmune hemolytic anemia (AIHA) is a rare disease in children, presenting with variable severity. Most commonly, warm-reactive IgG antibodies bind erythrocytes at 37 °C and induce opsonization and phagocytosis mainly by the splenic macrophages, causing warm AIHA (w-AIHA). Post-infectious cold-reactive antibodies can also [...] Read more.
Autoimmune hemolytic anemia (AIHA) is a rare disease in children, presenting with variable severity. Most commonly, warm-reactive IgG antibodies bind erythrocytes at 37 °C and induce opsonization and phagocytosis mainly by the splenic macrophages, causing warm AIHA (w-AIHA). Post-infectious cold-reactive antibodies can also lead to hemolysis following the patient’s exposure to cold temperatures, causing cold agglutinin syndrome (CAS) due to IgM autoantibodies, or paroxysmal cold hemoglobinuria (PCH) due to atypical IgG autoantibodies which bind their target RBC antigen and fix complement at 4 °C. Cold-reactive antibodies mainly induce intravascular hemolysis after complement activation. Direct antiglobulin test (DAT) is the gold standard for AIHA diagnosis; however, DAT negative results are seen in up to 11% of warm AIHA, highlighting the need to pursue further evaluation in cases with a phenotype compatible with immune-mediated hemolytic anemia despite negative DAT. Prompt supportive care, initiation of treatment with steroids for w-AIHA, and transfusion if necessary for symptomatic or fast-evolving anemia is crucial for a positive outcome. w-AIHA in children is often secondary to underlying immune dysregulation syndromes and thus, screening for such disorders is recommended at presentation, before initiating treatment with immunosuppressants, to determine prognosis and optimize long-term management potentially with novel targeted medications. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
►▼ Show Figures

Figure 1

19 pages, 430 KiB  
Review
Infectious Complications in Autoimmune Hemolytic Anemia
by Juri Alessandro Giannotta, Bruno Fattizzo, Francesca Cavallaro and Wilma Barcellini
J. Clin. Med. 2021, 10(1), 164; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10010164 - 05 Jan 2021
Cited by 17 | Viewed by 7013
Abstract
Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. [...] Read more.
Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
►▼ Show Figures

Figure 1

17 pages, 980 KiB  
Review
Rituximab Use in Warm and Cold Autoimmune Hemolytic Anemia
by Irina Murakhovskaya
J. Clin. Med. 2020, 9(12), 4034; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9124034 - 13 Dec 2020
Cited by 10 | Viewed by 10392
Abstract
Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia, less than 50% of patients remain in long-term remission following [...] Read more.
Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia, less than 50% of patients remain in long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder that requires therapy in the majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first-line as well as relapsed settings. Rituximab is the preferred therapy for steroid refractory warm autoimmune hemolytic anemia (wAIHA) and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of rituximab and the current literature on its role in the management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
►▼ Show Figures

Figure 1

19 pages, 1594 KiB  
Review
New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy
by Wilma Barcellini, Anna Zaninoni, Juri Alessandro Giannotta and Bruno Fattizzo
J. Clin. Med. 2020, 9(12), 3859; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123859 - 27 Nov 2020
Cited by 57 | Viewed by 18371
Abstract
Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease due to increased destruction of autologous erythrocytes by autoantibodies with or without complement involvement. Other pathogenic mechanisms include hyper-activation of cellular immune effectors, cytokine dysregulation, and ineffective marrow compensation. AIHAs may be primary or [...] Read more.
Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease due to increased destruction of autologous erythrocytes by autoantibodies with or without complement involvement. Other pathogenic mechanisms include hyper-activation of cellular immune effectors, cytokine dysregulation, and ineffective marrow compensation. AIHAs may be primary or associated with lymphoproliferative and autoimmune diseases, infections, immunodeficiencies, solid tumors, transplants, and drugs. The direct antiglobulin test is the cornerstone of diagnosis, allowing the distinction into warm forms (wAIHA), cold agglutinin disease (CAD), and other more rare forms. The immunologic mechanisms responsible for erythrocyte destruction in the various AIHAs are different and therefore therapy is quite dissimilar. In wAIHA, steroids represent first line therapy, followed by rituximab and splenectomy. Conventional immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporine) are now considered the third line. In CAD, steroids are useful only at high/unacceptable doses and splenectomy is uneffective. Rituximab is advised in first line therapy, followed by rituximab plus bendamustine and bortezomib. Several new drugs are under development including B-cell directed therapies (ibrutinib, venetoclax, parsaclisib) and inhibitors of complement (sutimlimab, pegcetacoplan), spleen tyrosine kinases (fostamatinib), or neonatal Fc receptor. Here, a comprehensive review of the main clinical characteristics, diagnosis, and pathogenic mechanisms of AIHA are provided, along with classic and new therapeutic approaches. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
►▼ Show Figures

Figure 1

22 pages, 360 KiB  
Review
Evans’ Syndrome: From Diagnosis to Treatment
by Sylvain Audia, Natacha Grienay, Morgane Mounier, Marc Michel and Bernard Bonnotte
J. Clin. Med. 2020, 9(12), 3851; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9123851 - 27 Nov 2020
Cited by 47 | Viewed by 13794
Abstract
Evans’ syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. [...] Read more.
Evans’ syndrome (ES) is defined as the concomitant or sequential association of warm auto-immune haemolytic anaemia (AIHA) with immune thrombocytopenia (ITP), and less frequently autoimmune neutropenia. ES is a rare situation that represents up to 7% of AIHA and around 2% of ITP. When AIHA and ITP occurred concomitantly, the diagnosis procedure must rule out differential diagnoses such as thrombotic microangiopathies, anaemia due to bleedings complicating ITP, vitamin deficiencies, myelodysplastic syndromes, paroxysmal nocturnal haemoglobinuria, or specific conditions like HELLP when occurring during pregnancy. As for isolated auto-immune cytopenia (AIC), the determination of the primary or secondary nature of ES is important. Indeed, the association of ES with other diseases such as haematological malignancies, systemic lupus erythematosus, infections, or primary immune deficiencies can interfere with its management or alter its prognosis. Due to the rarity of the disease, the treatment of ES is mostly extrapolated from what is recommended for isolated AIC and mostly relies on corticosteroids, rituximab, splenectomy, and supportive therapies. The place for thrombopoietin receptor agonists, erythropoietin, immunosuppressants, haematopoietic cell transplantation, and thromboprophylaxis is also discussed in this review. Despite continuous progress in the management of AIC and a gradual increase in ES survival, the mortality due to ES remains higher than the ones of isolated AIC, supporting the need for an improvement in ES management. Full article
(This article belongs to the Special Issue Diagnosis and Management of Autoimmune Hemolytic Anemias)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-8
Back to TopTop