Cold Autoimmune Hemolytic Anemia Research Articles

Cold-antibody Autoimmune Hemolytic Anemia: its Association with Neoplastic Disease and Impact on Therapy.

Cold-antibody mediated autoimmune hemolytic anemia (cAIHA) is subclassified as cold agglutinin disease (CAD), secondary cold agglutinin syndrome (CAS), and paroxysmal cold hemoglobinuria (PCH). This review aims to address the occurrence of neoplastic disorders with these three entities and analyze the impact of such neoplasias on treatment for cAIHA. "Primary" CAD is a distinct clonal B-cell lymphoproliferative disorder in probably all cases, although not classified as a malignant lymphoma. CAS is secondary to malignant lymphoma in a minority of cases. Recent findings allow a further clarification of these differential diagnoses and the therapeutic consequences of specific neoplastic entities. Appropriate diagnostic workup is critical for therapy in cAIHA. Patients with CAD should be treated if they have symptomatic anemia, significant fatigue, or bothersome circulatory symptoms. The distinction between CAD and CAS and the presence of any underlying malignancy in CAS have essential therapeutic implications.

A national survey of current immunohematologic testing practices for the diagnosis of autoimmune hemolytic anemia in India.

Autoimmune hemolytic anemia (AIHA) is a common term for several disorders that differ from one another in terms of etiology, pathogenesis, clinical features, and treatment. Management of patients with AIHA has become increasingly evidence-based in recent years. While this development has resulted in therapeutic improvements, it also carries increased requirements for optimal diagnosis using more advanced laboratory tests. Unfortunately, limited data are available from developing countries regarding the testing and transfusion management of patients with AIHA. The main objective of this survey was to explore the current immunohematologic testing practices for the diagnosis of AIHA in India. This online survey consisted of 30 questions, covering the place of work, the number of AIHA cases encountered in the 3 preceding years, testing method(s), transfusion management, and so forth. Individuals representing 89 laboratories completed the survey; only 78 of which responded that AIHA testing was performed in their facility's laboratory. The majority of respondents agreed that the most commonly affected age-group comprised individuals of older than 20 years, with a female preponderance. Regarding transfusion management, respondents indicated that transfusion with "best-match" red blood cell units remains the most common practice. Column-agglutination technology is used by 92 percent of respondents as the primary testing method. Although a monospecific direct antiglobulin test is available at 73 percent of the sites, most of them have limited access to other resources that could diagnose cold or mixed AIHA. Merely 49 percent of responding laboratories have the resources to perform adsorption studies for the detection of alloantibodies. Furthermore, three-cell antibody screening reagents are unavailable at 32 percent of laboratories. In 72 percent of centers, clinical hematologists would prefer to consult a transfusion medicine specialist before administering treatment to AIHA patients. There is unanimous agreement regarding the need for a national registry. The survey data indicate wide variability in testing practices for patients with AIHA in India. Future studies are needed to focus on the feasibility and cost-effectiveness of different testing strategies for developing countries.

Cold Autoimmune Hemolytic Anemia as First Clinical Manifestations in Systemic Lupus Erythematosus (SLE) in Young Female Patient, a Rare Association: Case Report

Background: Cold autoimmune hemolytic anemia” is very uncommon in systemic lupus erythematous (SLE), and until now a small number of similar reports have been published in scientific papers. Case presentation: Here, we present a nineteen-year-old female patient who admitted with cold type hemolytic anemia, pancytopenia and was later diagnosed to have SLE. Conclusion: Despite the very rare association between SLE and cold autoimmune hemolytic anemia (AIHA), this case report improves clinical practice regarding considering SLE as one of the differential diagnoses in cold AIHA, to provide early diagnosis and optimal management.

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.

Splenic Marginal Zone Lymphoma complicated with cold autoimmune haemolytic anaemia

Splenic Marginal Zone Lymphoma (SMZL) is a distinct subtype of Marginal Zone Lymphoma (MZL) which is categorized under Non-Hodgkin Lymphoma. It is usually benign with the potential to transform into diffuse large B-cell lymphoma. Comorbid cold Autoimmune Haemolytic Anaemia(cAHA) is rare with SMZL. A case of a 53-year-old woman is presented here. She presented with fever and anaemic symptoms. Biochemical, radiological and histological investigations were done, and a diagnosis of SMZL complicated with cAHA was made.

A rare cause of Acquired Hemolytic Anemia in a child; Donath-Landsteiner antibody

Abstract Introduction/Objective INTRODUCTION: The Donath-Landsteiner (DL) antibody is known to cause paroxysmal cold hemoglobinuria (PCH), a rare form of intravascular hemolytic anemia which is precipitated by an IgG biphasic hemolysin with specificity to the P blood group antigen and most commonly reported in children. The DL test is a serologic test specifically examines, the biphasic nature of the antibody activity. Methods/Case Report CASE PRESENTATION: A 4-year-old previously healthy boy presented at an academic medical center with rhinorrhea and nasal congestion. His family reported that his urine became darker almost coke colored after his symptoms started. His initial vitals; temperature of 37.1 C, heart rate of 140, blood pressure of 122/87 and O2 saturation of 96% on room air. Laboratory investigations showed a hemoglobin level of 4.2 g/dL, hematocrit level of 12.5%, platelets count of 229 K/uL, indirect bilirubin of 6.2mg/dL, haptoglobin <30 mg/dL, LDH >1800 U/L. Direct antiglobulin test was positive with complement only. Thermal Amplitude and indirect Donath-Landsteiner tests were both positive. Respiratory viral panel was positive for Rhinovirus. The antibody screen was negative, and the patient was provided supportive care including as needed RBC transfusion, warming of fluids and body. By day day 9 patient Hgb stabilized, LDH, bilirubin and haptoglobin normalized and his urine turned yellow color and was discharged in stable condition. Results (if a Case Study enter NA) NA Conclusion CONCLUSIONS PCH is classified as a cold autoimmune hemolytic anemia caused by an IgG antibody that sensitizes RBCs at cold temperatures by attaching complement to the RBCs, causing intravascular hemolysis upon rewarming. The DL test for PCH involves in vitro testing for hemolysis with the patient's serum, washed group-O cells expressing the P antigen, and fresh normal serum. To prevent autoadsorption of the antibody and hemolysis, blood should be collected in prewarmed tubes that do not contain anticoagulants and kept at 37°C during the collection procedure. A high index of suspicion especially in pediatric population should be maintained after a viral infection. The treatment is usually supportive.

Mutations in Histone Lysine Methyltransferase Genes Are Associated with Autoimmune Cytopenias

Introduction Epigenetic mechanisms are important in regulation of gene expression by modifying chromatin structure to facilitate DNA accessibility (Lau et al Nat Immunol. 2018). DNA methylation and histone modifications are critical for the pathogenesis of hematologic malignancies and autoimmune diseases (Surace et al Front Immunol. 2019) Alterations in enzymes involved in histone modification are associated with immunodeficiencies, including Kabuki syndrome (KS), a rare genetic disorder associated with autoimmune cytopenias, such as immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) (Margot et al J Am Coll Med Genet 2020) caused by loss-of-function KMT2D and KDM6A mutations. Somatic mutations in the KMT2D gene have also been observed in patients with Cold Agglutinin Disease. (Małecka et al Br J Haematol. 2018). Aims: The aims of this study are: 1) to identify the frequency of mutations in histone methyltransferase genes (MT) KMT2D, KMT2A, KMT2C and KDM6A in patients with autoimmune cytopenias, and 2) to compare clinical, laboratory and immunological characteristics, and response to therapy in patients with or without mutation in MT and autoimmune cytopenias (AIC). Methods Data mining software from the electronic medical record was used to identify patients ≥ 18 years with a diagnosis of AIC, including ITP, warm and cold AIHA, autoimmune neutropenia, and Evans Syndrome (ES), who had Next Generation Sequencing (NGS) performed. Cytopenias due to malignancy, nutritional deficiency, medications, pregnancy, or infection were excluded. Patients were categorized into two groups based on the presence or absence of mutation in the MT genes (MT+, MT-) with variant allelic frequency (VAF) > 2%. Demographic, laboratory, and clinical characteristics, treatment outcomes, and NGS sequencing data were collected and compared between groups. Next, KMT2 mutations seen in patients with AIC were cross-referenced against the 1000 Genome Project (1000GP) population database to evaluate the frequency of polymorphisms in the general population (Auton et al Nature 2015). CADD in silico prediction algorithm was used to score the potential deleterious effect of MT mutations (Kirchner Nat Genet. 2014). Chi-Square test was used for categorical variables. Statistical analysis was completed in R software. Results Among 495 patients who underwent NGS, 79 (16%) had a mutation in MT genes. These mutations were present in 36% of patients with AIC as compared to 13% in those without AIC (p=0.0005). Among 55 patients with AIC, mutations in the MT genes were present in 20 patients (MT+), 35 patients did not have these mutations (MT-). KMT2C mutations were seen in 10 (50%) patients, KMT2D mutations in 9 patients (45%, one patient had two KMT2D mutations), 1 patient (5%) had both KMT2C & KMT2D variants (Figure 1). The median VAF was 39.5% (IQR, 15.45 - 49.80). The MT+ group had a significantly higher proportion of Hispanic (60% vs 31%) and non-Hispanic White patients (25% vs 14%), p=0.038, Table 1. The median age at diagnosis for the MT+ cohort was younger compared to MT- (45.5 vs 58 years old, respectively), though not statistically significant. AIC diagnoses in both groups were ITP (44%) wAIHA (22%) cAIHA (9%) Autoimmune Neutropenia (2%), and ES (24%). Compared to the MT- group, the MT+ group had lower IgG levels (p=0.0041) and absolute lymphocyte count (p=0.041). MT+ patients with AIHA were more likely to have positive Direct Coombs and complement involvement. No significant differences were found in median nadir hemoglobin and platelet counts, need for therapy, or median number of lines of therapy. Best overall response to therapy was similar in the two groups (93%), with more complete responses in MT- group (55% vs 33%) though not statistically significant. Next, we assessed KMT2 polymorphisms in the general population. Most of the polymorphisms were not present in the 1000GP database and none had a frequency > 0.001. The average Phred score was 19.8; 12/20 patients had Phred score > 20, suggesting that most mutations are in the top 1% of the deleterious variants. Conclusion We report for the first time that patients with autoimmune cytopenias have a high frequency of variants in MT genes. Median allelic frequency close to 50% suggests potential germline predisposition to immune dysregulation and autoimmunity however further studies are needed to better understand the impact of these observations.

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.

Autoimmune Haemolytic Anaemia, Acute Pericarditis with Cardiac Tamponade as Presenting Manifestations in Systemic Lupus Erythematosus- A Rare Case Report

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that affects mostly young women in which tissue-binding autoantibodies and immune complexes cause damage to organs and tissues. SLE is characterised by aberrant immunological responses that result in the release of higher levels and immunogenic nucleic acids, proteins, and other self-antigens. Autoimmune Haemolytic Anaemia (AIHA) is a condition in which antibodies against red blood cells are present. It is classified as a warm and cold antibody AIHA. The causes of warm antibody AIHA are autoimmune illnesses, infections, or even malignancy. The presence of Immunoglobulin G (IgG) antibodies can indicate warm autoimmune haemolytic anaemia (warm agglutinin anaemia), which is characterised by fatigue and other constitutional symptoms. Although, autoimmune haemolytic anaemia can be a component of the SLE spectrum, warm autoimmune haemolytic anaemia as the first manifestation of SLE is exceedingly rare. This case report describes a case of a 23-years-old female who presented to the hospital with complaints of breathlessness and chest pain. After evaluation she was found to have pericardial tamponade and AIHA. Pericardiocentesis was done and further investigations confirmed the diagnosis of SLE. She was treated with injectable methylprednisolone, injectable antibiotics, Tab. hydroxychloroquine, Tab. febuxostat ,Tab. colchicine, oral antidiuretic, oral levothyroxine and other supportive management. The lack of unambiguous pathognomonic characteristics or tests, coupled with the variable presentation of SLE, makes diagnosis tricky. Overall, AIHA can be an initial presentation as well as a part of other disease processes, emphasising the significance of a comprehensive work in patients with AIHA.

Autoimmune Haemolytic Anaemia, Acute Pericarditis with Cardiac Tamponade as Presenting Manifestations in Systemic Lupus Erythematosus- A Rare Case Report

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder that affects mostly young women in which tissue-binding autoantibodies and immune complexes cause damage to organs and tissues. SLE is characterised by aberrant immunological responses that result in the release of higher levels and immunogenic nucleic acids, proteins, and other self-antigens. Autoimmune Haemolytic Anaemia (AIHA) is a condition in which antibodies against red blood cells are present. It is classified as a warm and cold antibody AIHA. The causes of warm antibody AIHA are autoimmune illnesses, infections, or even malignancy. The presence of Immunoglobulin G (IgG) antibodies can indicate warm autoimmune haemolytic anaemia (warm agglutinin anaemia), which is characterised by fatigue and other constitutional symptoms. Although, autoimmune haemolytic anaemia can be a component of the SLE spectrum, warm autoimmune haemolytic anaemia as the first manifestation of SLE is exceedingly rare. This case report describes a case of a 23-years-old female who presented to the hospital with complaints of breathlessness and chest pain. After evaluation she was found to have pericardial tamponade and AIHA. Pericardiocentesis was done and further investigations confirmed the diagnosis of SLE. She was treated with injectable methylprednisolone, injectable antibiotics, Tab. hydroxychloroquine, Tab. febuxostat ,Tab. colchicine, oral antidiuretic, oral levothyroxine and other supportive management. The lack of unambiguous pathognomonic characteristics or tests, coupled with the variable presentation of SLE, makes diagnosis tricky. Overall, AIHA can be an initial presentation as well as a part of other disease processes, emphasising the significance of a comprehensive work in patients with AIHA.

Cold agglutinin autoimmune haemolytic anaemia as an initial presentation of diffuse large B cell lymphoma

Cold agglutinin disease, commonly affecting females in the their seventh decade of life, is otherwise a rare entity and has an incidence of one case per million people per year. Cold reactive antibody is associated with autoimmune haemolytic anaemia (AIHA) in approximately 20% of the cases. Although the occurrence of AIHA in patients with non-Hodgkin's lymphomas is well known, aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL) initially presenting as cold agglutinin AIHA is extremely rare. Here, we describe a case of DLBCL presenting few months before the diagnosis as cold antibody-AIHA.

The role of serological and molecular testing in the diagnostics and transfusion treatment of autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare autoimmune disease characterised by haemolysis associated with the presence of immunoglobulins and/or components of the complement system on red blood cells (RBCs). It is classified into warm or cold antibody-mediated AIHA according to the temperature at which autoantibodies bind optimally to RBCs. Clinicians should be familiar with the procedural tests used for a complete laboratory investigation of AIHA. Good collaboration between clinicians and laboratory specialists with correct sample handling and an exact diagnostic work-up is extremely important for the correct classification and proper therapeutic management of AIHA. Specialised serological test procedures are very complex. Problems with serological testing may be excluded with the molecular testing, which has now become a gold standard to predict a patient's phenotype in order to secure the right antigen-matched blood for AIHA patients. More recently, genotyping has been used instead of serological typing and complex adsorption tests. This paper offers a description of various tests for differentiating between types of AIHA. A diagnostic algorithm and the problems of laboratory investigation are also presented, and an application of molecular methods for the blood group typing in AIHA is elaborated.

A case report of cold autoimmune haemolyticanaemia in pulmonary tuberculosis

Autoimmune hemolyticanemia (AIHA) can be caused by a variety of etiologies. Approximately one-half of warm AIHAs are idiopathic, while the nonidiopathicetiologies include lymphoproliferative disorders, autoimmune disease, and infection-induced AIHA. AIHA may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Here we reported an extraordinary case of Mycobacterium tuberculosis infection presented with high titer cold-agglutinin autoimmune hemolysis in an immunocompetent patient. Although being risk factors for mortality, infections are an underestimated issue in AIHA. No antecedent case of pulmonary tuberculosis associated with cold agglutinin disease has been reported from Malaysia. Bangladesh Journal of Medical Science Vol. 21 No. 03 July’22 Page: 754-757

Rare case of self-limiting haemolysis associated with Dengue fever in a Sri Lankan female – case report

A 61-year old female with dengue haemorrhagic fever developed anaemia and rising transaminase levels on the 6th day of illness. She was found to have haemolysis with a negative direct antiglobulin test (DAT), and no red cell fragmentation. She recovered with supportive care. Haemolysis with associated Haemolytic uraemic syndrome (HUS), Disseminated intravascular coagulation (DIC) and cold Auto-immune haemolytic anaemia (AIHA) is reported previously; DAT negative haemolytic anaemia associated with dengue fever has not. This case suggests a need for further studies on other immune mechanisms that can lead to haemolysis with dengue fever.

Thrombotic risk in autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is a type of anemia caused by the destruction of red blood cells due to autoantibodies targeting membrane proteins. AIHA is divided into two types based on the thermal amplitude: warm AIHA (at 37°C) and cold AIHA (at <37°C). Anemia and jaundice are the major symptoms of AIHA, and in cold agglutinin disease the peripheral circulation disturbance deteriorates patients' quality of life. Cumulative evidence has revealed that both types of AIHA increase the risk of thrombosis and intravascular hemolysis appears to be the most critical factor in the pathogenesis. Complement activation plays an important role in the intravascular hemolysis of AIHA, though the coagulation and hemostatic systems and the crosstalk between these systems also contributes significantly to the pathogenesis of thrombosis. Future treatment of AIHA should be targeted at not only alleviating anemia but also reducing thrombotic risk.

Advances in understanding the pathogenesis and treatment of autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is caused by damaged red blood cells due to auto-antibodies targeting its membrane proteins. The heterogeneous group of diseases is divided into two types depending on the thermal amplitude of autoantibodies: warm and cold AIHA. Cold AIHA includes cold agglutin disease and paroxysmal nocturnal hemoglobinuria. AIHA is also divided into primary and secondary AIHA depending on its etiology. Recent advances in understanding the pathogenesis have revealed that AIHA brings not only anemia but also thromboembolic risk or impaired quality of life (QOL). This review describes its pathogenesis, diagnostic approach, and treatment strategies based on the latest information.

COVID-19 and Immune-Mediated RBC Destruction.

ObjectivesTo summarize the epidemiologic, clinical, and laboratory characteristics of autoimmune hemolytic anemia (AIHA) secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination.MethodsWe conducted a systematic review using standardized keyword search to identify all reports of SARS-CoV-2 infection or vaccination and AIHA across PubMed, Web of Science, Scopus, and Google Scholar through September 24, 2021.ResultsFifty patients (mean [SD] age, 50.8 [21.6] years) diagnosed with coronavirus disease 2019 (COVID-19) and AIHA were identified. AIHA subtypes and number of patients were as follows: cold AIHA (n = 18), warm AIHA (n = 14), mixed-type AIHA (n = 3), direct antiglobulin test (DAT)–negative AIHA (n = 1), DAT-negative Evans syndrome (n = 1), Evans syndrome (n = 3), and subtype not reported (n = 10). Mean (SD) hemoglobin at AIHA diagnosis was 6.5 [2.8] g/dL (95% confidence interval, 5.7-7.3 g/dL). Median time from COVID-19 symptom onset to AIHA diagnosis was 7 days. In total, 19% (8/42) of patients with COVID-19–associated AIHA with reported outcomes were deceased. Four patients (mean [SD] age, 73.5 [16.9] years) developed AIHA following SARS-CoV-2 vaccination: Pfizer-BioNTech BNT162b2 vaccine (n = 2); Moderna mRNA-1273 vaccine (n = 1); undisclosed mRNA vaccine (n = 1). AIHA occurred after 1 dose in 3 patients (median, 5 days).ConclusionsSARS-CoV-2 infection and vaccination are associated with multiple AIHA subtypes, beginning approximately 7 days after infectious symptoms and 5 days after vaccination.

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

Hairy cell leukemia unmasked by COVID-19 associated autoimmune hemolytic anemia

Hairy cell leukemia (HCL) belongs to a heterogeneous group of B-cell malignancies, which can occasionally be detected in asymptomatic patients. Herein, we report a case of HCL discovered due to the management of the hemolytic episode of cold-antibody autoimmune hemolytic anemia (cAIHA)&nbsp; developed during the course of a mild form of coronavirus disease 2019 (COVID-19).&nbsp; Neither the AIHA nor the underlying HCL did affect the course of COVID-19, but the indolent course of HCL showed to have been changed into a clinically overt disease.

WARM AGGLUTIN AUTOIMMUNE HEMOLYTIC ANEMIA ASSOCIATED WITH EPSTEIN BARR VIRUS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Autoimmune hemolytic anemia (AIHA) is a relatively rare disorder (1-3 per 100 000) characterized by antibody production against autologous erythrocytes [1]. We present a novel case of warm agglutinin, autoimmune hemolytic anemia associated with Epstein-Barr Virus (EBV). CASE PRESENTATION: A 79-year-old woman with hypothyroidism was referred from the outpatient clinic after labs showed hemoglobin (Hgb) of 6.7 mg/dL. She complained of fatigue and dyspnea for 5 days. She had yellowing of skin and dark urine for 2 days. Vitals showed a blood pressure of 87/27 mmHg with a heart rate of 87 bpm. Repeat Hgb was 4.7 g/dL associated with mean corpuscular volume 111.6 fL. White cell count was elevated at 18. Leukocyte Alkaline Phosphatase score was elevated at 50. Direct Coombs test was positive with IgG and anti-C3 with warm agglutins. Haptoglobin was <10mg/dL, Lactate dehydrogenase 900U/L, and ferritin 1747. She received 3 units of packed red blood cells (RBC) and was started on corticosteroids. Peripheral blood smear showed left shift with increased bands, and megaloblastic granulocytes. Serum B12 level was 63ng/mL (N >200). Intrinsic factor was within normal limits. Ebstein Barr Virus IgG titers were elevated at 50 times limit upper limit of normal. All other tests for infectious causes of AIHA were negative. She was not on any medications known to cause AIHA. The patient reported resolution of symptoms by admission day 2. Hgb improved to baseline at 9.4 mg/dL and repeat MCV was 94.8 fL. The patient was subsequently discharged with B12 supplementation and continued to be symptom-free 4 weeks later. DISCUSSION: AIHA has a broad differential, with etiologies including medications, viruses, and hematological malignancies. EBV has a well-established connection with cold agglutin AIHA. IgM antibodies formed against EBV can cross-react against erythrocytes, reacting at 1-3 degrees Celsius, hence classified as cold agglutinin hemolytic anemia. However, it is not known if EBV can also induce warm agglutination. An extensive literature review returned a single report of fatal AIHA due to IgG warm agglutination exacerbated by EBV [2]. AIHA may have also be exacerbated by irregular erythropoiesis. Megaloblastic erythrocytes may have unique membrane antigens that present easier targets for circulating antibodies, thus driving hemolysis [3].Macrocytosis was likely due to B12 deficiency in this case, however other autoimmune diseases like pernicious anemia may be associated with AIHA, and warrant investigation. LAP score was also done to differentiate between reactive leukocytosis vs hematological malignancies such as chronic myelogenous leukemia, which also causes AIHA. CONCLUSIONS: EBV is classically associated with cold agglutin AIHA, although this case suggests that warm agglutination is possible. Macrocytic anemia may also worsen AIHA. Further studies are needed to delineate causation. REFERENCE #1: Hill A, Hill QA. Autoimmune hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2018;2018(1):382-389. doi:10.1182/asheducation-2018.1.382 REFERENCE #2: Fadeyi EA, Simmons JH, Jones MR, Palavecino EL, Pomper GJ. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus. Lab Med. 2015 Winter;46(1):55-9. doi: 10.1309/LM9OWRF64OGQODEA. PMID: 25617394. REFERENCE #3: Vucelic V, Stancic V, Ledinsky M, Getaldic B, Sovic D, Dodig J, Grbac L, Gacina P, Rincic G, Carzavec D. Combined megaloblastic and immunohemolytic anemia associated--a case report. Acta Clin Croat. 2008 Dec;47(4):239-43. PMID: 19388472. DISCLOSURES: No relevant relationships by Mateus Fernandes, source=Web Response