Mixed Autoimmune Hemolytic Anemia Research Articles

Mixed Autoimmune Hemolytic Anemia - A Rare Case Report

Abstract Mixed autoimmune hemolytic anemia (MAIHA) is a rare clinical condition where both warm and cold antibodies cause red cell destruction, leading to anemia. MAIHA can present as a blood group discrepancy or crossmatch incompatibility, which can be very challenging for transfusion medicine services to diagnose and issuing of best-matched blood. Therefore, a comprehensive immunohematology workup, including a monospecific direct antiglobulin test, and indirect antiglobulin test is performed to determine the thermal amplitude and titer of autoantibodies. It is important to be aware of this phenomenon because, like warm AIHA and MAIHA should be treated immediately, with steroids. We hereby report a case of a 14-year-old girl presenting with a history of generalized weakness and dizziness; preliminary investigations revealed anemia, increased reticulocyte count, and antinuclear antibodies positive. Hence, further diagnosis of MAIHA associated with systemic lupus erythematosus was made. A high-dose steroid therapy was given to the patient, and significant improvement was seen clinically.

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.

Cold Agglutinin Disease (CAD) Real-World Evidence (CADENCE) Registry: Update to the Study Design of the First International, Prospective CAD Registry

Cold agglutinin disease (CAD) is a rare chronic autoimmune hemolytic anemia (AIHA) characterized by classical complement pathway (CP)-mediated hemolysis. CAD is associated with a substantial disease burden negatively impacting quality of life (QoL), including severe fatigue, and increased risk of both thromboembolic events and early mortality. Due to the rarity of CAD, there is scarce information regarding its natural history, long-term impacts, and complications. Sutimlimab, a humanized monoclonal antibody that selectively inhibits the CP, is the first approved treatment for CAD. In the CARDINAL and CADENZA Phase 3 trials, sutimlimab reduced hemolysis, anemia, was generally well tolerated, and meaningfully improved QoL. The CADENCE Registry (NCT05791708) is a large international database of patients with CAD or cold agglutinin syndrome (CAS, a cold antibody-driven hemolytic anemia associated with an underlying condition). First launched in 2019, the first study patient was enrolled in 2022 following a COVID-19 pandemic-related hiatus. Presented here is an update on the current CADENCE protocol and study design. CADENCE is a multinational, multicenter, observational, prospective, longitudinal registry study enrolling patients ≥18 years of age diagnosed with CAD (diagnostic criteria: a monospecific direct antiglobulin test strongly positive for C3d and negative or weakly positive for immunoglobulin G and a cold agglutinin titer ≥1:64) or CAS (CAD diagnostic criteria, with causative infection, autoimmune disorder or overt malignancy). Exclusion criteria include patients with a diagnosis of warm or mixed AIHA and those actively participating in a CAD/CAS interventional trial. The main study objective is to better understand patient demographics, clinical characteristics, treatment patterns, healthcare resource utilization (HRU), natural history of disease, long-term clinical outcomes, and impact on patient QoL. A sutimlimab-treated cohort sub-study is ongoing to assess the real-world safety and effectiveness of sutimlimab in patients with CAD, fulfilling the regulatory commitment for a post-authorization safety study. The enrollment period is expected to last ~3 years and patients will be followed for 3 years after the last patient enrolled. Data collection will include both clinical assessments as per standard of care and patient-reported outcome (PRO) data collected at enrollment and at ~6-month interval follow-ups. Additional safety data will be collected for the sutimlimab cohort. The CADENCE Registry's first patient enrolled (after study restart) was in Q2 2022, with last patient's first visit expected in Q2 2025 and last patient's last visit expected in 2028 ( Figure). The registry will collect data on ~400 patients with CAD/CAS across ~90 sites in 8 countries: Austria, France, Germany, Italy, Japan, Spain, the UK, and the US. Among them, ≥30 patients with CAD treated with sutimlimab are expected to take part in the cohort study. Key data to be collected include clinical characteristics, disease complications, comorbidities, mortality, treatment regimens, HRU, and PROs. Biomarkers for hemolysis will be assessed, including lactate dehydrogenase, haptoglobin, total and indirect bilirubin. In the sutimlimab cohort, data will also be collected on adverse events (AEs), serious AEs, and AEs of special interest (serious infections, Raynaud's, arterial hypertension, autoimmune disorders, hypersensitivity/anaphylaxis, exposure in pregnancy, overdose). PRO measures include the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue, the 36-item Short Form Health Survey (SF-36), and the CAD symptoms and impact questionnaire (CAD-SIQ), a novel 11-item questionnaire specifically designed for CAD. Interim analyses will occur annually. Final analyses will be performed at study end both at regional and global levels. As of July 13, 2023, 47 of 82 targeted sites have been activated, and 113 of 405 targeted patients (CAD/CAS) have been enrolled, including 13 sutimlimab-treated patients. CADENCE is the first global registry for patients with CAD and will help advance understanding of the natural history and disease process of this rare condition. This registry will also assess the long-term safety and effectiveness of sutimlimab in patients with CAD in a real-world setting, providing clinicians with data that may help improve treatment practices.

Rare case of refractory mixed autoimmune hemolytic anemia in a 6-year-old child: a case report

BackgroundMixed autoimmune hemolytic anemia (AIHA) shows combined clinical and laboratory characteristics of warm and cold AIHA. It is relatively uncommon in children. Consequently, knowledge about mixed AIHA prevalence, clinical presentation, treatment options, and prognosis in children is limited to very few case reports.Case presentationWe describe a six-year-old Asian girl presenting with profound anemia, blood group typing discrepancy and crossmatch incompatibility, post upper respiratory tract infection. Detection of red cell warm and cold reactive autoantibodies, led to the diagnosis of mixed AIHA. Autoantibodies with laboratory evidence of hemolysis persisted despite high dose steroid therapy. Due to the inability to wean further, the patient was subsequently commenced on mycophenolate mofetil to which she seems to be responding.ConclusionsMixed AIHA may be notoriously difficult to diagnose and treat. Detailed clinical and laboratory work-up is essential to establish the diagnosis. To the best of our knowledge, this is the first case report of mixed AIHA following upper respiratory tract infection. Awareness of this occurrence is important, as similar to warm AIHA, mixed AIHA should be treated immediately by early initiation of steroid therapy. In addition, prompt supportive care as well as long-term clinical follow-up are required to improve outcomes of these cases.

Is Splenectomy still the best treatment for Autoimmune hemolytic anemia

Introduction:
 Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases that includes AIHA with warm type antibodies, cold agglutinin disease (CAD), mixed type AIHA, paroxysmal cold hemoglobinuria, and atypical AIHA.
 Currently CAD is defined as chronic, clonal lymphoproliferative disease, while presence of cold agglutinin in gastrointestinal tract is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies against red blood cells (RBCs), these antibodies cause premature destruction of erythrocytes. The pathogenesis of AIHA is complex and still not yet fully understood.
 Aim of study:
 The purpose of the study was to review the literature on the treatment options for Autoimmune Hemolytic Anemia
 Materials and methods: A systemic review was conducted using PubMed, ScienceDirect, Google Scholar databases. The search strategy was based on following terms: Aiha, splenectomy autoimmune anemia, aiha treatment,
 Results and Conclusions:
 Based on the review of the medical literature, we believe that Splenectomy is no longer the most effective method of treating any type of AIHA and the Rituximab treatment presented by us seems to be safer and definitely less burdensome for the patient.
 Of course, splenectomy is still used in AIHA - but nowadays it is more limited due to the very high effectiveness of the described non-surgical treatment

Utility of dithiothreitol in a case of spontaneous autoagglutination due to mixed autoimmune hemolytic anemia in a child – A rare scenario

Utility of dithiothreitol in a case of spontaneous autoagglutination due to mixed autoimmune hemolytic anemia in a child – A rare scenario

Transfusion challenges and use of best match blood transfusion in autoimmune hemolytic anemia patients: Experience from a Tertiary Care Hospital of South India

Background and Objectives: In autoimmune hemolytic anemia (AIHA) patients, there is decreased survival of red blood cells (RBCs) because of increased destruction by patients' autoantibodies. Due to decreased survival of RBCs, there is an increase in erythropoiesis and other biochemical parameters of hemolysis. One of the vital tests in AIHA is direct Coombs test (DCT). In this study, we share our experience on the difficulties faced by us during the compatibility testing and providing transfusion support to these patients. Methods: This is a retrospective study done in the department of transfusion medicine in a tertiary care hospital of South India. Patients from January 2020 to March 2021 with the diagnosis of AIHA requiring transfusion were included in this study. A total of 136 patients with positive DCT with AIHA diagnosis requiring transfusion support were included in our study. Results: Out of 136 cases, 58% (n=79) of patients had incompatibility during cross matching while in 42% (n=57) had cross matched compatible unit. In all incompatible cases best match blood was transfused. Most transfusions were done for patients with DCT Grade 4+. Out of 45 patients with mixed AIHA, 40 (88.8%) patients required a transfusion (P < 0.05). Of that 104 patients with transfusion support, 66 (63%) were with primary AIHA and 38 (36.04%) with secondary AIHA. Conclusion: It is tough and challenging to get compatible units in AIHA patients. Best-matched blood is useful when transfusion becomes essential during life-threatening anemia.

Hyperhemolysis in the Setting of Mixed-Autoimmune Hemolytic Anemia: A Rare Complication of COVID-19

SARS-CoV-2 is a novel human pathogen known for its predilection for the respiratory system. Herein, we present a unique case in which a patient developed hyperhemolysis in the setting of mixed autoimmune hemolytic anemia secondary to SARS-CoV-2. A 33 years-old male with a past medical history of resolved immune thrombocytopenic purpura (ITP) presented to the hospital with symptoms of jaundice after being infected with SARS-CoV-2. On admission, his Hgb was 12.5g/dL. Lab results showed indirect bilirubin of 13mg/ dL, LDH at 759 U/L, Haptoglobin &lt;10 and the percent reticulocyte count was 2.33%. A DAT was also positive for C3, IgG, anti-E, in addition to both warm and cold autoantibodies. PCR was positive for COVID-19. Within two days of admission, his Hgb dropped to 5.9g/dL. A total of seven units of pRBC was required to achieve an Hgb of 6g/dL in 48 hours. Patients with preexisting hematological abnormalities have a propensity to develop AIHA in the setting of the virus. The majority of the cases described in the literature were associated with warm autoimmune hemolytic anemia. Our patient tested positive for both warm and cold antibodies, which may partially explain the mechanism behind hyperhemolysis in our patient.

Characteristics and Outcome of Adults with Severe Autoimmune Hemolytic Anemia Admitted in Intensive Care Unit: Results from a Large French Observational Study

Characteristics and Outcome of Adults with Severe Autoimmune Hemolytic Anemia Admitted in Intensive Care Unit: Results from a Large French Observational Study

P.077 Mixed autoimmune hemolytic anemia: an unusual cause of ischemic stroke and extensive cerebral microbleeds

Background: Mixed autoimmune hemolytic anemia (mAIHA) is a rare autoimmune disorder that results in hemolysis with thrombotic complications like ischemic stroke. This is the first case report of cerebral microbleeds secondary to mAIHA. Methods: A literature review of mAIHA and cerebral microbleeds was conducted using the PubMed and Ovid MEDLINE databases from 1980 to 2021. Results: A 76 year old male with congenital deafness and rheumatoid arthritis presented with diffuse livedo reticularis and abdominal pain. He had fulminant hemolysis with new neurologic deficits and altered mental status. CT/CTA of the head and neck were unremarkable. MR brain revealed extensive cerebral microbleeds and multi-territory ischemic strokes. He was diagnosed with mAIHA, started on pulse methylprednisolone, and had no further microbleeds on follow-up MRI. From his clinical picture, common causes of cerebral microbleeds were ruled out such as cerebral amyloid angiopathy and hypertension. The pathogenesis of his microbleeds may be from concomitant severe hypoxia or a prothrombotic state, both previously reported in the literature. Conclusions: This is the first case report of extensive cerebral microbleeds secondary to mAIHA. When a patient develops acute neurologic deficits in the context of mAIHA, extensive cerebral microbleeds may be present possibly due to concomitant severe hypoxia versus a prothrombotic state.

False-positive fourth-generation HIV test associated with autoimmune hemolytic anemia. Case report

Introduction: The fourth-generation ELISA human immunodeficiency virus (HIV) screening test has a high sensitivity and specificity &gt;99% to detect both antigens and antibodies. Estimates are that only 0.5% yield false positive results.Case description: 61-year-old female patient with a clinical picture consisting of malaise, unquantified fever, asthenia and adynamia. Laboratory tests revealed anemia, so a Coombs test was performed, obtaining a positive result along with other findings of mixed autoimmune hemolytic anemia. Two fourth-generation ELISA HIV screening tests were performed obtaining positive results. Given the national recommendations on the diagnosis of HIV infection, a viral load was performed, which turned out to be negative, so the result was considered a false positive.Discussion: Clinical and biological factors are related to false positive results. There are descriptions about autoimmunity phenomena, such as systemic lupus erythematosus or autoimmune hemolytic anemia, with few cases in older adults.Conclusions: Rapid tests have changed the diagnosis of HIV infection worldwide; however, like any other diagnostic test, they may yield false positive results with differential diagnoses, including autoimmune hemolytic anemia.

Successful treatment of severe idiopathic mixed autoimmune hemolytic anemia with bortezomib and intravenous immunoglobulin

Introduction: Autoimmune hemolytic anemia (AIHA) is a rare and diverse group of acquired hemolytic anemias which results from increased destruction of red blood cells (RBCs) due to autoantibodies directed against antigens on the RBC surface. Currently, there are no clearly defined evidence-based guidelines on the management of AIHA, and current treatment options are based on small retrospective studies, case reports, as well as expert experiences and recommendations. We report a case of severe idiopathic mixed AIHA that responded to a combination of steroids, intravenous immunoglobulin (IVIG) and bortezomib. Case Report: A 25-year-old African American female presented with jaundice, shortness of breath, and abdominal pain. She had splenomegaly on examination and initial work-up was significant for severe anemia (hemoglobin, 3.3 g/dl) and hyperbilirubinemia (total bilirubin, 26.7 mg/dl; direct bilirubin, 21.9 mg/dl). Direct antiglobulin test (DAT) was microscopically positive for anti-IgG and anti-C3d, and cold autoantibodies were identified. An extensive workup for a possible secondary cause of her anemia was non-revealing. She was sequentially treated with prednisone, IVIG, and bortezomib. Marked response was noted as evidenced by improvement in the hemoglobin from a nadir of 3.2 g/dl on admission to 10.1 at discharge. Patient has remained clinically in remission since then. Conclusion: The first line treatment for warm AIHA (w-AIHA) includes glucocorticoids and transfusion of least incompatible RBCs. Steroids are rarely necessary or effective in cold agglutinin AIHA in which case high dose IVIG and plasmapheresis have been used albeit with inconsistent results. Bortezomib is an inhibitor of the 26S proteasome and is approved for the treatment of multiple myeloma. It has been reported to have some activity in rituximabresistant cold agglutinin disease (CAD) due to its activity against the CD20-negative plasma cell compartment that may be responsible for IgG anti-RBC autoantibody production.

Seasonal Variation in Autoimmune Hemolytic Anemia: A National Database Analysis

Background:Autoimmune hemolytic anemia (AIHA) is a decompensated acquired hemolysis caused by host's immune system acting against its own red cell antigens. Serologically, it can be divided to warm hemolytic anemia, cold hemolytic anemia, paroxysmal cold hemoglobinuria and mixed AIHA. Pathogenesis of AIHA comprises of a series of complex interactions between genetics, environmental either conferring to protective or deteriorating effects. Among these, climatic changes appears to be key as it involves many triggers such as viral infections, temperature and other host factors. We reviewed a large national hospitalization database to determine whether rates of autoimmune hemolytic anemia have a seasonal variation over the past decade.Methods:We examined the Nationwide Inpatient Sample (NIS), a nationally representative survey of hospitalizations conducted by the Healthcare Cost and Utilization Project in collaboration with participating states. It is the largest all-payer inpatient dataset in the United States and includes a 20% sample of United States community hospitals that approximates 20% of all US community hospitals. The Nationwide Inpatient Sample (NIS) database was used to estimate annual number of hospitalizations from 2000 - 2012. Identification of autoimmune hemolytic anemia related hospitalizations was based on the designation of the prior validated International Classification of Diseases (9th Edition) Clinical Modification (ICD-9-CM) diagnosis code 283 as the principal discharge diagnosis. The frequency of hospitalization per month cumulative over 13 years was calculated and divided by number of days in that month to determine the mean hospitalizations per day for each month. All calculations were carried out using the weighted estimates approximating nationwide population estimates.Results:An estimated 48,416 hospitalizations with primary diagnosis of autoimmune hemolytic anemia occurred in the US from 2000 to 2012 as per NIS database. More specifically, the mean number of hospitalizations per day in each month is shown in Fig. 1. The mean number of hospitalizations each day was highest in November (141 per day) and thereafter the hospitalization rate dropped to a nadir in May (122 per day). There was a significant rising trend of admissions from June towards winter months with peaks in November as depicted in the Fig.1. In general, the number of hospitalization was maximum in the winter months and minimum in summer months as demonstrated in Fig.2.Conclusion:We identified for the first time in United States an impressive pattern of seasonal variation in hospitalizations for autoimmune hemolytic anemia with a notable increase in winter and fall and a significant drop during summer months. The seasonal pattern may reflect viral or other triggers for immune system activation. Further efforts need to be made to identify triggers and methods to determine the relationship of these variations and reduce this predictive burden on the overall health care system. DisclosuresNo relevant conflicts of interest to declare.

Autoimunitní hemolytická anémie

Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies directed against self red blood cell (RBC) surface antigens. A consequence may be an intravascular hemolysis mediated by activated complement or extravascular hemolysis caused by destruction of complex of RBC with autoantibody in spleen and liver. The basic classification subdivides AIHA in primary/idiopathic and secondary with known underlying disease. A classification according to the thermal range of antibody recognizes warm AIHA, cold aglutinin disease (CAD), mixed AIHA and paroxysmal cold hemoglobinuria. Pathogenesis of AIHA consists of a defective antigen presentation to immunocompetent cells, insufficient process of T-lymphocyte tolerance to autoantigens and induction of autoantibody production by B-lymphocytes. For the diagnosis of AIHA are essential direct and indirect antiglobulin tests. The first-line therapy for warm AIHA is still administration of corticosteroids. For non-responding patients, second-line treatment includes rituximab or splenectomy. Combination of other immunosuppressive drugs represents a third-line treatment for resistant/relapsing patients. Rituximab is a treatment of choice for patients with CAD. Key words: anemia hemolytic - autoimmunity - corticosteroids - diagnosis - pathogenesis - rituximab - splenectomy - treatment.

Immunohematological and clinical characterizations of mixed autoimmune hemolytic anemia.

BACKGROUND AND AIM:Patients with warm autoimmune hemolytic anemia (AIHA) may carry immunoglobulin (Ig) M antibodies that react at room temperature and are nonpathological, but few may have cold agglutinins that react at or above 30°C and are referred to as “mixed” AIHA (MAIHA). Here, we present our experience on characterizing MAIHA both clinically and serologically.MATERIALS AND METHODS:Out of 134 AIHA patients, 13 diagnosed as MAIHA were subjected to detailed immunohematological characterization. Most patients were severely anemic and required urgent transfusions. Resolution of blood group discrepancy, elution, Donath-Landsteiner test, and adsorption study were performed following established protocol. “Best match” blood units were selected and transfused to patients.RESULTS:Eight of the 13 patients had severe hemolysis. The median age of patient was 37 years with a female preponderance and secondary MAIHA was observed in 8 (61.5%) patients. Blood group discrepancy was encountered in 4 (30.8%) patients. Multiple red cell bound autoantibodies and high titer serum-free IgM autoantibodies were detected in all samples. Twenty-nine units of “best match” packed red blood cells were transfused to 12 patients without any adverse reaction. Improvement in hematological and biochemical values was observed in all follow-up patients.CONCLUSION:Patients with MAIHA often present with severe hemolysis necessitating blood transfusions. While red cells are coated with multiple autoantibodies, both warm reactive IgG and cold reactive IgM autoantibodies are present in the serum. These serological complexities not only render a crossmatch incompatibility but often lead to blood group discrepancy. “Best match” blood transfusion is always lifesaving.

Resolving Serological Blood Group Discrepancy and Providing Transfusion Support in a Patient of Mixed Auto Immune Hemolytic Anemia: A Case Report

Resolving Serological Blood Group Discrepancy and Providing Transfusion Support in a Patient of Mixed Auto Immune Hemolytic Anemia: A Case Report

Autoimmune hemolytic anemia: transfusion challenges and solutions

Autoimmune hemolytic anemia: transfusion challenges and solutions Melca M O Barros, Dante M Langhi Jr, Jos&eacute; O Bordin Department of Clinical and Experimental Oncology, Universidade Federal de S&atilde;o Paulo, S&atilde;o Paulo, Brazil Abstract: Autoimmune hemolytic anemia (AIHA) is defined as the increased destruction of red blood cells (RBCs) in the presence of anti-RBC autoantibodies and/or complement. Classification of AIHA is based on the optimal auto-RBC antibody reactivity temperatures and includes warm, cold-reactive, mixed AIHA, and drug-induced AIHA subtypes. AIHA is a rare disease, and recommendations for transfusion are based mainly on results from retrospective data and relatively small cohort studies, including heterogeneous patient samples or single case reports. In this article, we will review the challenges and solutions to safely transfuse AIHA patients. We&nbsp;will reflect on the indication for transfusion in AIHA and the difficulty in the accomplishment of immunohematological procedures for the selection of the safest and most compatible RBC units. Keywords: hemolytic anemia, RBC autoantibodies, autoimmunity, hemolysis, direct &shy;antiglobulin test

Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances.

Diagnosis and treatment of autoimmune hemolytic anemia: classic approach and recent advances.

Thirteen Year Retrospective Analysis Of Adult Patients With Autoimmune Hemolytic Anemia At The Cleveland Clinic: Responses To Therapy

Background and ObjectiveTreatment of autoimmune hemolytic anemia (AIHA) is complicated by disease heterogeneity and a high propensity for relapse. Most cases of AIHA are mediated by warm and cold-reactive autoantibodies, as defined by the direct antiglobulin test (DAT), and the treatment approach differs depending on the subtype. Evidence supporting use of specific AIHA treatments is limited to retrospective studies, small series, or case studies. To address this issue, a retrospective analysis of all patients with AIHA treated at the Cleveland Clinic from January 2000 to April 2013 was performed. MethodsPatients were included if they were ≥ 18 years old and presented with a new diagnosis or relapse of AIHA. Frequencies of complete responses (CR) or partial responses (PR) were recorded, and the median time to relapse measured using the Kaplan-Meier method. PR was defined as a nontransfused hemoglobin of ≥ 10 mg/dL with a hemoglobin increase of ≥ 2 mg/dL, while CR was defined as a nontransfused hemoglobin of ≥ 12 mg/dL, hemoglobin increase ≥ 2 mg/dL, and normalization of hemolytic markers. The duration of high dose and total corticosteroid therapy was recorded. Results180 patients were identified. 122 (69%) presented with warm antibody-mediated AIHA, 42 (24%) with cold antibody-mediated AIHA, 6 (3%) with mixed AIHA, and 8 (4%) with DAT negative AIHA. 97 (54%) were females. 61% of patients were between the ages of 50 and 80. Steroids were used in 82 patients with warm AIHA, 14 patients with cold AIHA, 3 patients with mixed AIHA, and 5 patients with DAT negative AIHA. Steroid response rates were 81% (27% CR, 54% PR) in warm AIHA, 85% (21% CR, 64% PR) in cold AIHA, 66% (33% CR, 33% PR) in mixed AIHA, and 80% (40% CR, 40% PR) in DAT negative AIHA. Median time to relapse was 14.3 months in warm AIHA, 3.6 months in cold AIHA, and 13 months in mixed AIHA; median time to relapse could not be determined in DAT negative AIHA. The mean duration of steroid use was 6.3 months in warm AIHA, 4.3 months in cold AIHA, 5.4 months in mixed AIHA, and 1.5 months in DAT negative AIHA. Rituximab was used in 23 patients with warm AIHA and 14 patients with cold AIHA, with overall response rates of 74% (17% CR, 57% PR) and 80% (27% CR, 53% PR), respectively. The median time to relapse was 8.5 months for warm and 55.2 months for cold AIHA after Rituximab treatment. In 15 patients with warm AIHA, splenectomy induced responses in 83% (33% CR, 50% PR) with a median time to relapse of 37.8 months. In 24 patients with warm AIHA and 7 patients with cold AIHA, treatment of the underlying disorder induced responses in 87% (33% CR, 54% PR) and 86% (29% CR, 57% PR), respectively. Median time to relapse was 22.1 months in warm AIHA and 16.5 months in cold AIHA. Other less commonly used treatments included immunosuppressants, intravenous immunoglobulin, and erythropoietin derivatives, with bortezomib and cold avoidance used in the cold AIHA group. When comparing warm and cold AIHA, no significant difference was found in total response rates to various treatments, including steroids (81% vs. 85%, p = 0.486), Rituximab (74% vs. 80%, p = 0.49), and treatment of the underlying condition (87% vs. 86%, p = 0.662). ConclusionsThis analysis demonstrated a surprisingly high response rate for corticosteroids in all subtypes of AIHA, though most responses in cold AIHA were partial and of relatively short duration. Rituximab was effective in both warm and cold antibody-mediated AIHA, with a high incidence of durable responses in the latter. Definitive treatment of the underlying condition was used less commonly, but was a highly effective approach for treating secondary AIHA. Splenectomy yielded durable remissions in most patients with warm AIHA. Disclosures:No relevant conflicts of interest to declare.

Clinical Heterogeneity Of Autoimmune Hemolytic Anemia: A 35-Years Retrospective Study Of 157 Patients

The clinical presentation of autoimmune hemolytic anemia (AIHA) is greatly heterogeneous, from mild/compensated to life-threatening forms. The aim of this study was to correlate the clinical and serological characteristics of the disease, usually classified as warm (WAIHA), cold (CHD), and mixed, based on the thermal and isotype characteristics of the anti-RBC antibody (IgG, IgM or both, respectively). One-hundred fifty seven AIHA patients (61 M and 96 F, median age 57, range 5-95) referred to our institution from 1978 to September 2012 were investigated. They had been followed-up for a median of 26 months (range 12-271), and 50% were still in follow-up. As regards the thermal characteristics 40% of cases were WAIHA, 32% CHD, 19% mixed forms and 9% atypical (12 DAT negative and 1 DAT positive for IgA only). Considering the severity of anemia at onset 33% of cases had Hb levels<6 g/dl, 34% Hb 6-8 g/dL, 18% Hb 8-10 g/dL, and 15% Hb>10 g/dL. The most severe AIHA cases were mainly mixed (18/30, 60% p=0.001) and atypical (6/13, 46%) forms, whereas only a small fraction of CHD was characterized by a severe onset (8/51, 16% p=0.002). Reticulocytopenia (<100.000 mmc) was more frequently observed in cases with severe onset (14/52, 27%), possibly contributing to the clinical picture. Eleven patients experienced an acute event at the onset of hemolysis and the majority of them (7/11, 63% ) were WAIHA; we recorded 4 deep venous thrombosis (with 2 subsequent pulmonary embolisms), 1 disseminated intravascular coagulation, 3 cardiac ischemic events, 2 acute renal failure and 4 acute infection (3 pneumonias and 1 sepsis); 18 patients died because of AIHA during the follow up. As regard therapy, we considered steroids, splenectomy, cytotoxic drugs and rituximab: 45% of cases (mostly WAIHA) were treated with steroids only, 23% with 2 lines, 10% with 3, and 6% with 4 or more lines; splenectomy was performed in 20 cases, mostly mixed and severe forms (p=0.001); 23 patients were treated with various cytotoxic drugs, and 33 with rituximab (the latter was more frequently administered in clinically severe cases, and in mixed and atypical forms, p=0.009). On the whole, the most severe patients were those who underwent 3 or more lines of therapy, compared with the other cases (14/52 versus 11/105, p=0.015). Finally, 16% of cases have never been treated, mostly CHD with mild anemia. Transfusions were performed in 65 cases, plasma-exchange in 3 (all with Hb<6 g/dL), and erythropoietin administered in 6 cases. Of note, the presence of an Hb value lower than 6 g/dL at onset was a risk factor for the requirement of 3 or more lines of therapy (odds ratio 3.148, CI 95% 1.312-7.552). Response rates to steroid therapy were similar in warm, cold, mixed and atypical AIHAs (on average 70%). Responses to rituximab were similar in cold and other AIHA forms (70-80%). Splenectomy, was ineffective in the 2 CHD who underwent surgery, whereas response rates were 63% in WAIHA and 80% in mixed and atypical cases. In conclusion, AIHAs showed a marked clinical heterogeneity, 1/3 of cases with a severe onset and with life threatening complications. These cases are frequently mixed or atypical forms and refractory to different therapies. Disclosures:No relevant conflicts of interest to declare.