Warm Autoimmune Hemolytic Anemia Research Articles

Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia

Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in two cohorts, one for patients with CAD and the other wAIHA. In each cohort, patients were randomly assigned to receive 270 or 360 mg/day pegcetacoplan for up to 48 weeks. Safety endpoints included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy endpoints included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Thirteen (100%) and 10 out of 11 (91%) patients with CAD and wAIHA respectively experienced at least 1 TEAE. Ten patients had at least 1 serious adverse event; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90 to 3.00) and 1.7 g/dL (-1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective in patients with CAD and wAIHA. Registered at www.clinicaltrials.gov (NCT03226678).

Parsaclisib for the treatment of primary autoimmune hemolytic anemia: Results from a phase 2, open-label study.

Autoimmune hemolytic anemia (AIHA) is a group of acquired autoimmune disorders characterized by red blood cell hemolysis. In a phase 2, open-label, multicenter study, adults with warm AIHA, cold agglutinin disease, or mixed-type AIHA were administered once-daily 1.0 or 2.5 mg parsaclisib (selective phosphoinositide 3-kinase δ inhibitor) orally for 12 weeks, followed by an extension period. Dose increases (for AIHA worsening) or decreases (for tolerability) were permitted. Primary efficacy endpoint was the proportion of patients with complete (≥12 g/dL hemoglobin [Hgb]) or partial (10-12 g/dL Hgb or ≥2 g/dL increase from baseline) response at any visit during weeks 6-12 not attributable to transfusion. Among 25 enrolled patients (median age, 63 y), 16 (64%) achieved a partial or complete Hgb response during weeks 6-12. Responses were observed by week 1 in 52.0% of patients with incremental improvements during weeks 6-12 and sustained responses during the extension period. Responses were higher among patients with warm AIHA versus other types (75.0% vs. 44.4%). Clinically meaningful improvements in Functional Assessment of Chronic Illness Therapy-Fatigue scores were observed at weeks 6 and 12. All patients had treatment-emergent adverse events (TEAEs), most commonly diarrhea (32.0%) and pyrexia (28.0%). Grade ≥3 TEAEs occurred in 13 patients (52.0%). TEAEs considered possibly related to treatment occurred in 11 patients (44.0%). No dose reductions were required; six patients (24%) discontinued for a TEAE. In summary, parsaclisib was well tolerated and resulted in substantial improvements in Hgb response at week 1, with durable responses through the extension period. CLINICAL TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT03538041).

Molecular testing in a patient with multiple alloantibodies and warm autoimmune hemolytic anemia: A case study

Abstract Introduction/Objective We present a case of RBC alloimmunization and warm autoimmune hemolytic anemia (WAIHA) in a patient with a recent RBC transfusion. Serological testing followed by molecular testing revealed a rare D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/- predicted phenotype. Methods/Case Report A 75-year-old black male with secondary myelofibrosis presented with a sudden onset of chest pain, dyspnea and weakness during an RBC transfusion. The patient was subsequently admitted for further workup. Labs showed low hemoglobin, low haptoglobin, elevated LDH and a positive direct antiglobulin (DAT) test. The patient was started on intravenous immunoglobulin and steroids for suspected WAIHA. On immunohematology serologic testing, blood typed as B-positive and polyspecific DAT positive with anti-IgG positive and anti-C3 negative. Serum plasma studies showed probable warm autoimmune hemolytic anemia and allo anti-S, -E, and -C by previous history. Eluate studies showed panagglutinin and antibody with D-like specificity. Immucor PreciseTypeTM Human Erythrocyte Antigen (HEA) Molecular BeadChip test predicted a partial e antigen and potential hrB-. Genotyping for RHD variants was performed and revealed RHD*01 (homozygous or hemizygous). Targeted genomic testing did not detect variants associated with common partial or weak RhD antigens. Based on this testing, the patient was not predicted to be at risk of allo-anti-D. An RHCE genotype for C, c, E and e variants including hrB and hrS showed RHCE*ce48C,733G/RHCE*ce733G with predicated phenotype of D+ C- E- partial c+ partial e+ VS+ V+ hrS+ hrB+vw/-. Based on the RHCE testing, the patient was predicted to be at risk for allo-anti-c, -e, -f (ce) and possibly anti-hrB. Results (if a Case Study enter NA) NA Conclusion In this case, serologic testing alone did not reveal a precise diagnosis. Molecular testing aided in the diagnosis of WAIHA and will help guide future transfusions. Pathologists must consider molecular testing when faced with a challenging serologic diagnosis.

Overall Survival and Treatment Patterns Among Patients With Warm Autoimmune Hemolytic Anemia in Sweden: A Nationwide Population-based Study.

Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody-mediated disorder, and first-line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden. Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan-Meier curves with log-rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long-term versus short-term (≥ 3 vs. < 3 months) OCS users. The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7-year follow-up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log-rank test: p = 0.003). Subgroup analyses showed no significant difference in risk of death between long-term and short-term OCS users; however, in the sensitivity analysis, long-term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; p < 0.001) versus short-term OCS users. Secondary wAIHA or long-term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments.

Mixed autoimmune hemolytic anemia as the initial presentation of systemic lupus erythematosus: A case report and review.

Autoimmune hemolytic anemia (AIHA) is an acquired condition caused by autoantibody mediated destruction of erythrocytes. AIHA is classified as warm or cold depending on whether the autoantibodies involved react optimally at or below body temperature (37°C), respectively. Mixed AIHA, with features of both, is rare and clinically more severe. We report a case of mixed AIHA that was found to be the presentation of systemic lupus erythematosus (SLE). Treatment with rituximab and prednisone resulted in good response. Although more commonly associated with warm AIHA, SLE can present with mixed AIHA.

Sutimlimab for Cold Agglutinin Disease.

Cold agglutinin disease (CAD) is a rare type of autoimmune hemolytic anemia (AIHA) distinct from warm antibody AIHA. One of the ways it is distinct is that CAD is usually not responsive to corticosteroids compared with warm antibody AIHA. Historically, CAD therapy has been limited to immunotherapy or chemoimmunotherapy with varying responses. Cold agglutinin disease also poses a risk for thrombosis and mortality. For patients, fatigue tends to be a common symptom of CAD. The hallmark of CAD is complement-mediated hemolysis, which makes complement inhibitors a critical therapeutic option for patients. Previously, eculizumab, a C5 inhibitor, had limited therapeutic effect for CAD. More recently, sutimlimab, a C1s inhibitor, was shown in two phase III studies to be an efficacious treatment for CAD, improving hemoglobin, hemolysis, and fatigue. However, there is a paucity of medical literature on CAD and on sutimlimab in particular that is geared toward advanced practice providers (APPs). This article aims to provide APPs with a background in CAD and a focus on sutimlimab, assisting these providers in caring for patients with CAD receiving this therapy.

Red cell serological characterization of autoimmune hemolytic anemia in systemic lupus erythematosus patients

Abstract: INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a clinical condition with increased red cell destruction or decreased red cell survival due to autoantibodies against self-antigens on red blood cells. AIHA may be primary or secondary to other underlying illness. Systemic lupus erythematosus (SLE) is the most common secondary cause of AIHA. Although the incidence of AIHA in SLE patients is low (5%–10%), sometimes, it causes severe anemia which requires blood transfusion. Characterization of these autoantibodies in AIHA is very important, because the clinical condition and treatment of the patient depend on the optimal temperature reactivity, class, and subclass of immunoglobulin responsible. AIM AND OBJECTIVES: The aim and objective of this study are to perform detailed characterization of red cell autoantibodies for accurate diagnosis of AIHA in SLE patients, to find out specific class (immunoglobulin G [IgG]/IgM/IgA) of immunoglobulin and/or complement (C3c/C3d) responsible for AIHA, and their association with severity of hemolysis. MATERIALS AND METHODS: This was a prospective analytical study, done at a tertiary care hospital in Hyderabad, conducted between February 2021 and May 2022. SLE patients with AIHA were included in the study. Monospecific direct antiglobulin test (DAT) was performed to identify the specificity of autoantibody or complement. Based on hematological laboratory values, the study population was divided into three groups, i.e., mild, moderate, and severe hemolysis. DAT strength, hemolytic parameters, and severity of hemolysis were compared between different types of AIHA in SLE patients. Correlation statistics were used to know the association of severe hemolysis with DAT strength and different combinations of autoantibodies. RESULTS: Among 150 patients enrolled, 16 (10.6%) patients had severe hemolysis, 51 (34%) patients had moderate hemolysis, and 83 (55.3%) patients had mild hemolysis. Only IgG was positive in 109 (72.6%) patients, both IgG and C3d were positive in 37 (24.6%) patients, C3d was positive in 4 patients, and IgM was positive in 19 patients. High DAT reaction strength (3+–4+) and presence of C3d or IgM along with IgG were moderately correlated with severe hemolysis. CONCLUSION: Warm AIHA is the most common type of AIHA in SLE patients mediated by IgG. Mild and moderate hemolysis was seen in most cases. Severe hemolysis was moderately correlated with the presence of C3d or IgM. Further studies are warranted to find the predisposing factors leading to severe hemolysis.

Mycophenolate Mofetil for the Treatment of Warm Autoimmune Haemolytic Anaemia Post-Rituximab Therapy: A Case Series.

Warm autoimmune haemolytic anaemia (wAIHA) is an acquired haemolytic disorder most commonly treated with a combination of corticosteroids, rituximab and/or splenectomy. Third-line therapies for refractory cases include immunosuppressive agents. Mycophenolate mofetil is frequently used in these scenarios, although its use is supported by small studies and anecdotal evidence rather than large-scale data. We describe three cases of refractory warm autoimmune haemolytic anaemia successfully treated with mycophenolate mofetil. Case 1: A persistent case of autoimmune haemolytic anaemia in a 56-year-old was ultimately managed with mycophenolate mofetil, leading to successful steroid tapering and stable haemoglobin levels without relapse. Case 2: A woman with a complex oncological history, including lymphoma and breast cancer, achieved remission with mycophenolate therapy, maintaining stability post-steroid treatment. Case 3: Mycophenolate proved effective for a 63-year-old with cirrhosis after recurrent autoimmune anaemia and deep vein thrombosis, enabling cessation of steroids and maintaining remission. Management of this condition can be challenging and balancing the available treatments is crucial to reduce potential complications from long-term therapies that appear to be ineffective. Our case series demonstrates anecdotal experience on successful use of mycophenolate mofetil for complex refractory cases of wAIHA. Warm autoimmune haemolytic anaemia can be a challenging condition to manage. Refractory cases that are steroid-dependent can benefit from trialling steroid-sparing agents such as mycophenolate.Anti-CD20 agents such as rituximab can be very effective in refractory cases, however there is a small percentage of patients that might not be responsive to this monoclonal antibody.Autoimmune haemolytic anaemias can be frequently complicated by thrombotic events, and part of the backbone treatment is establishing good thromboprophylaxis.

Current Management of Warm Autoimmune Haemolytic Anaemia and Recent Advancements in Research: Interview with a Key Opinion Leader

Warm autoimmune haemolytic anaemia (wAIHA) is a rare, life-threatening disorder caused by autoantibodies that lead to the premature destruction of erythrocytes (haemolysis). There is currently no licensed targeted therapy for wAIHA. Until recently, there has been little research attention on autoimmune haemolytic anaemias (AIHA), with few developments in the field over the past 20 years. The last 3 years have seen a surge in research interest in wAIHA, with the development of potential new therapies for this rare disorder. For this article, the EMJ conducted an interview in June 2024 with key opinion leader, Bruno Fattizzo, from the University of Milan, and Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, to raise awareness of wAIHA, and explore recent advancements in research on this disease. Fattizzo, who has a wealth of experience and expertise in the clinical management of wAIHA, provided valuable insights into topics such as the clinical and quality of life (QoL) impact of wAIHA on the patient; current management of wAIHA, including steroids, rituximab, immunosuppressants, splenectomy, anticoagulant prophylaxis, and recombinant erythropoietin; and remaining unmet needs in the disease area. Also discussed were potential future therapies for this autoimmune disorder, including tyrosine kinase inhibitors, neonatal fragment crystallisable receptor (FcRn) inhibitors, and B cell activating factor receptor (BAFF-R) antagonists, and the challenges involved in managing patients with wAIHA. Finally, Fattizzo described the patient experience of living with wAIHA, proposed how best to raise awareness of wAIHA among healthcare professionals, the scientific community, patients, and the public, and outlined what the future of the management of patients with wAIHA might look like.

Anti-B-Cell-Activating Factor (BAFF) Therapy: A Novel Addition to Autoimmune Disease Management and Potential for Immunomodulatory Therapy in Warm Autoimmune Hemolytic Anemia.

Although rituximab is not specifically approved for the treatment of warm autoimmune hemolytic anemia (WAIHA), the First International Consensus Group recommends considering its use as part of the initial therapy for patients with severe disease and as a second-line therapy for primary WAIHA. Some patients do not respond to rituximab, and relapses are common. These relapses are associated with elevated B-cell-activating factor (BAFF) levels and the presence of quiescent long-lived plasma cells (LLPCs) in the spleen. A new group of immunomodulatory drugs, B-cell-activating factor inhibitors (BAFF-i), demonstrated efficacy in multiple autoimmune diseases and have the potential to improve WAIHA treatment outcomes by targeting B-cells and LLPCs. This article reviews the role of BAFF in autoimmune disorders and the currently available literature on the use of BAFF-directed therapies in various immunologic disorders, including WAIHA. Collectively, the clinical data thus far shows robust potential for targeting BAFF in WAIHA therapy.

A case of infectious mononucleosis caused by Epstein-Barr virus complicated by autoimmune hemolytic anemia

We represent a rare clinical case of infectious mononucleosis with hepatitis, caused by Epstein-Barr virus, complicated by rare secondary autoimmune hemolytic anemia associated with warm agglutinins in a 16-year-old patient. The disease was long-lasting, with a two-wave course of febrile fever. Signs of hepatitis with the development of anemia of moderate severity appeared during the second wave of febrile fever. The etiology of the disease was confirmed by the detection of Epstein-Barr virus DNA in blood and the detection of anti-VCA IgM antibodies to Epstein-Barr virus in the absence of anti-EBNA IgG antibodies. Hemolytic anemia was verified using markers of hemolysis (increased lactate dehydrogenase activity, decreased haptoglobin concentration), and positive results of a direct Coombs test. After successful initiation of prednisone therapy and clinical improvement, the patient was discharged from the hospital on the 24th day of disease to continue treatment on an outpatient basis (prednisone was replaced by methylprednisolone).This case demonstrates the development of a rare autoimmune complication in infectious mononucleosis caused by the Epstein-Barr virus.

The treatment strategies of autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is characterized by the accelerated destruction of erythrocytes due to the presence of antibodies and/or complement that bind to antigens on erythrocytes. It can be subdivided into warm, cold or mixed AIHA based on the type of autoantibody and the optimal temperature of antigen-antibody reaction. Glucocorticoid with or without rituximab is the first-line treatment of warm AIHA (wAIHA), and splenectomy was once the preferred second-line treatment for relapsed or refractory wAIHA. However, due to the various complications of splenectomy, rituximab has gradually become the preferred treatment for patients who have failed glucocorticoid therapy. Other available treatments including immunosuppressants and plasma exchange can be chosen. Rituximab with or without bendamustine is generally taken as the first-line regimen for cold autoimmune hemolytic anemia (cAIHA), while glucocorticoid and splenectomy are ineffective. Sutimlimab, a kind of complement inhibitor, has been approved for the treatment of cold agglutinin disease (CAD). In recent years, many new drugs have emerged as treatment options for AIHA. Emerging therapies, including B-cell-directed therapies, plasma cell-directed therapies, complement inhibitors, and phagocytosis inhibition, provide a new perspective for AIHA therapy, showing great potential for clinical applications.

Challenges in the diagnosis and management of autoimmune hemolytic anemia: A case-based approach. Experience from a tertiary care hospital in the Haryana region.

Autoimmune hemolytic anemia (AIHA) is a rare immune disorder which occurs when antibodies are directed against self red blood cells (RBCs) leading to hemolysis. AIHA is widely classified as warm autoimmune hemolytic anemia, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria and rarely drug induced AIHA. The pathogenesis of AIHA is complex interplay between genetic predisposition, immune dysregulation and enviornmental triggers. A direct antiglobulin test can be used to assess the immunological origin of the hemolysis in order to diagnose AIHA after identifying laboratory and clinical symptoms of hemolysis. The objective is to understand underlying mechanism in AIHAs, and usage of targeted therapies to modulate specific components of the immune response. We are hereby presenting a case series of 11 clinically suspected cases of AIHA in collaboration with their clinical features, immuno-hematological and other laboratory parameters, Flow cytometric analysis of lymphocyte subset in relevant cases, underlying etiology as well as serological subtype are also included. Majority of the patients were categorized as secondary AIHA (7/11, 63.63%). Out of 11 cases 7 were serologically subtyped as warm AIHA (7/11, 63.63%) ,2 cases were DaaT negative AIHA (2/11;18.18%), 2 cases were characterized as mixed AIHA subtype (2/11, 18.18%). Accurate subtyping of AIHA requires a systematic immunohematological approach coupled with comprehensive evaluations of clinical, hematological, and biochemical parameters.

Severe, Refractory Primary Warm Autoimmune Hemolytic Anemia Requiring 90 Erythrocyte Transfusions.

A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.

Efficacy and Safety of Weekly Bortezomib-dexamethasone as the Third-Line Therapy for Warm Autoimmune Hemolytic Anemia: a Case Series of 5 Patients

Efficacy and Safety of Weekly Bortezomib-dexamethasone as the Third-Line Therapy for Warm Autoimmune Hemolytic Anemia: a Case Series of 5 Patients

Autoimmune Hemolytic Anemia: A Review

Autoimmune hemolytic anemia (AIHA) is defined as an anemia caused by the destruction of red blood cells by antibodies directed against the patient's own red blood cell surface antigens. Different forms of AIHA are distinguished based on the characteristics of the antibody responsible for the disease. The most common form (70% of cases) is warm antibody autoimmune hemolytic anemia. These antibodies become active at temperatures between 35°C and 40°C. This type of hemolysis occurs mainly within tissues, particularly in the spleen. The diagnosis of AIHA relies on rigorous interpretation of immunohematological parameters, as well as additional tests to exclude associated diseases. In "idiopathic" cases, it is recommended to continue monitoring elderly patients beyond remission to detect the possible occurrence of lymphoma or myelodysplastic syndrome. Corticosteroid therapy is the standard treatment, but it can lead to numerous side effects. The efficacy of rituximab appears particularly promising in "refractory" forms of AIHA, and its use in the early phase of management to spare corticosteroid therapy should be evaluated in a prospective and randomized study.

Healthcare resource utilization of patients with warm autoimmune hemolytic anemia initiating first line therapy of oral corticosteroids with or without rituximab.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020-3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = 'index date') with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients (~ 60% female, mean age > 64 years). Over the 1-year follow-up, HCRU was higher in the OCS + R cohort with higher mean number of physician office visits (22.9 and 14.4; p < 0.01), including hematology/oncology office visits, and higher utilization of rescue therapy (59.7% and 33.3%; p < 0.01), driven by higher use of injectable corticosteroids. Patients in OCS + R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively (p = 0.24). In the majority of patients, second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS + R and 72.0% OCS cohorts (p = 0.31) initiated 2L in a mean of 218.3 and 203.2 days (p = 0.76) after the end of 1L treatment, respectively. The addition of rituximab in 1L did not extend the remission period, with most patients in both cohorts initiating 2L therapy within less than 1 year of completing 1L treatment. 1L OCS + R patients also had substantial HCRU burden. More effective novel therapies are needed to address the high unmet need in wAIHA.

Warm Autoimmune Hemolytic Anemia with Chronic Hepatitis B

Introduction: Warm autoimmune hemolytic anemia (wAIHA) is caused by erithrocytes destruction by IgG or IgG plus C3d-mediated autoantibody. Long use steroids are first line therapy of wAIHA. It has risk infection reactivation, like chronic hepatitis B. Case report: Man, 64 y.o, hospitalized with diagnosis wAIHA and chronic hepatitis B. Diagnosis of wAIHA is built by: severe normocytic normochromic anemia, reticulocytosis 42.29%, increasing lactate dehydrogenase 397 U/L, direct Coombs test (+4), antibody screening IgG (+4). Anothers laboratorium findings: HbsAg (+), albumin 3.5 g/dL, ALT U/L, rapid HIV (-), anti HCV (-). There is no blast found in peripheral blood and bone marrow smear. Patient also diagnosed chronic hepatitis B inactive phase with negative HbeAg, HBV DNA 547 IU/L, normal liver finding in abdominal USG and moderate fibrosis from fibroscan. Washed red cell transfussion was administered, 2 x 125 mg methilprednisolone iv (3 days) tapering off until to 40 mg/day doses. He did not get antiviral prophylaxis and be planned to reevaluate in next 6 months. Conclusion: Steroid is first line therapy in wAIHA. When wAIHA is diagnosed, determination of chronic hepatitis B status should confirmed. There is a risk of reactivation of chronic hepatitis B infection so monitoring is needed.

Current recommendations for the diagnosis and treatment of autoimmune hemolytic anemia based on etiology and pathology

Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies that can be divided into two types-warm and cold-depending on their thermal amplitudes. The pathology differs depending on the type of autoantibody involved; however, the underlying etiology can differ even when the pathology is the same. Therefore, understanding the underlying mechanisms and making an accurate diagnosis is critical, as inappropriate treatment not only results in treatment failure, but can also cause life-threatening complications and reduce patient quality of life. Corticosteroids are the first-line treatment for warm AIHA, but have limited efficacy against cold agglutinin disease (CAD). Moreover, long-term and high-dose administration of corticosteroids increases risk of infection, fracture, and thromboembolism. A novel therapeutic agent for CAD targeting the complement system is effective only against hemolysis, but does not improve symptoms induced by red blood cell aggregation. In addition, elderly patients who present with either warm AIHA or CAD should also be assessed for possible malignancy. This review discusses the etiologies and pathological conditions associated with AIHA and describes the recommendations for diagnosis and treatment according to the Japanese guideline for AIHA revised in 2022.

Cold agglutinin disease: pathology, diagnosis, and treatment

Cold agglutinin disease (CAD), an immune hemolytic disease mediated by the classical complement-dependent pathway, accounts for approximately 8% of autoimmune hemolytic anemia (AIHA) cases. Primary CAD is a clonal B-cell lymphoproliferative disease of the bone marrow that produces IgM type-M protein, while conventional secondary CAD is cold agglutinin syndrome (CAS). Clinical findings are broadly classified into chronic anemia due to hemolysis and symptoms associated with peripheral circulatory failure due to erythrocyte aggregation under cold exposure. Not all patients require drug therapy, but monoclonal antibody therapy against complement C1s is preferred for the former presentation and B-cell suppressors for the latter. As cold AIHA is treated differently than warm AIHA, misdiagnosis can significantly impact the outcome of treatment. The most important aspect of blood testing is temperature control of specimens. Cold agglutinin titer, IgM quantification, electrophoresis, and immunofixation methods may produce false-negative results if the serum is not temperature-controlled at 37-38°C until serum separation. Correct handling of specimens, along with knowledge of the various clinical features of CAD, will lead to correct diagnosis and appropriate treatment.