Cold autoimmune hemolytic anemia with myelodysplastic syndrome: Not just an “Open and Shut case”

Myelodysplastic syndromes (MDSs) are clonal hematopoietic stem cell neoplasms characterized by bone marrow failure leading to ineffective hematopoiesis, dyspoiesis, and cytopenias with a risk of progression to acute leukemia. Immunological syndromes have been reported to occur along with MDS in literature. However, cold autoimmune hemolytic anemia (AIHA) has rarely been reported in association with MDS. Herein, we report a case of an elderly male who presented with fever and cytopenias. He was being treated as a case of megaloblastic anemia in the past with no response to therapy. At present admission, the peripheral blood smear examination revealed red cell agglutination, thrombocytopenia with 4% blasts. Cold agglutinin disease was confirmed by a thermal agglutination test and bone marrow evaluation showed adequate megakaryocytes with 10% blasts; consistent with the diagnosis of MDS with excess blasts (MDS-EB2). Cytogenetic studies revealed multiple abnormalities. This report is being discussed in view of its rarity of presentation of cold AIHA with MDS.

Enfermedad por aglutininas frías: proceso diagnóstico, tratamiento y seguimiento de un paciente / Cold agglutinin disease: diagnosis, treatment and follow-up of a patient

La enfermedad por crioaglutininas es una anemia hemolítica autoinmune que se caracteriza, en la gran mayoría de los casos, por la hemólisis mediada por autoanticuerpos de tipo IgM y complemento C3d, contra los antígenos de la membrana del eritrocito, que conduce a hemólisis extravascular con propensión a la trombosis, y que afecta principalmente al sexo femenino y personas mayores. Su diagnóstico se realiza con la prueba de Coombs directo y fraccionado, y la titulación de aglutininas frías >1:64 a 4 °C. Se describe el caso clínico de una mujer de 89 años con un síndrome constitucional y una anemia de 3 años de evolución, en quien se determinó el diagnóstico de enfermedad por aglutininas frías. Asimismo, se describe el abordaje diagnóstico, el tratamiento instaurado, y se hace una breve revisión de la literatura publicada

Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia characterized in the vast majority of cases by hemolysis mediated by IgM autoantibodies and complement C3d against erythrocyte membrane antigens, leading to extravascular hemolysis with propensity to thrombosis, affecting mainly females and older individuals. It is diagnosed by direct and fractionated Coombs test and a cold agglutinin titer >1:64 at 4 °C. We describe the case of an 89-year-old woman with a constitutional syndrome and a 3-year history of anemia, who was diagnosed with cold agglutinin disease. Also, we include the diagnostic and treatment approach, and a brief review of the literature

Cold agglutinin disease related mismatch between hematocrit and hemoglobin values

Autoimmune hemolytic anemia is a disease characterized by destruction of red blood cells (RBC) and anemia, caused by production of antibodies released against the body’s own RBCs. While this condition is more commonly idiopathic, it may accompany autoimmune diseases as well. Cold agglutinin disease (CAD) is a rare subtype of acquired autoimmune hemoliytic anemia, however, is an idiosyncratic clinical and pathological terminology, usually seen in older ages. This condition is caused by IgM antibodies called “cold agglutinins” formed against I antigens on RBC membranes which cause agglutination of RBCs at lower temperatures. In this case, a 56 year old male patient who was diagnosed with CAD secondary to Epstein-Barr virus (EBV) infection is being presented.

Primera serie de casos reportada en Colombia de la enfermedad por aglutininas frías primaria y secundaria. Experiencia de un centro de referencia en Medellín entre 2010 y 2017 / First case series reported in Colombia of primary and secondary cold agglutinin disease. Experience of a reference center in Medellín between 2010 and 2017

RESUMEN Introducción: la enfermedad por aglutininas frías (EAF) es un trastorno hematológico primario o secundario, caracterizado por la anemia hemolítica autoinmune causada por los anticuerpos IgM a bajas temperaturas. Clínicamente, presenta parestesias y acrocianosis inducidos por frío y fiebre, aunque también puede ser asintomática y solo identificarse por alteraciones en el hemograma. Objetivo: describir las manifestaciones clínicas y de laboratorio, las causas primarias y secundarias de la EAF y compararlas con series de casos descritos en la literatura. Materiales y métodos: análisis retrospectivo de datos clínicos de pacientes del Hospital Universitario San Vicente Fundación de Medellín con resultados positivos para aglutininas frías. Dichos análisis se realizaron en el laboratorio de hematología de la Universidad de Antioquia, consideramos como positivo título ≥ 1: 64 o con la prueba de Coombs directa y positiva para anticuerpos fríos. Resultados: se incluyen los títulos de crioaglutininas de 23 casos con EAF: 6 formas primarias, 4 asociadas con los linfomas no Hodgkin (LNH), 8 secundarias a enfermedades infecciosas y autoinmunes y, 5 asociados con enfermedades misceláneas. Discusión y conclusiones: esta es la primera serie de casos en Colombia de EAF. La edad y género fueron similares a los datos reportados en la literatura. Observamos un mayor número de pacientes que presentaban anemia hemolítica y con síntomas asociados al frío. La relación hemoglobina hematocrito fue 1:2. Dentro de las causas secundarias destacamos las vasculitis, el lupus y la malaria. De las causas primarias las más frecuentes fueron los LNH, específicamente, el linfoplasmocítico. El tratamiento más utilizado para pacientes con EAF primaria incluyo rituximab.

SUMMARY Introduction: Cold agglutinin disease (CAD) is a primary hematologic disorder or can be secondary to another disease. CAD is characterized by autoimmune hemolytic anemia associated with IgM type antibodies, at low temperatures. Clinically CAD is associated with cryoparesthesia and acrocyanosis induced by cold and fever, or it can be asymptomatic and can be detected by abnormalities on cell blood counts. Objective: To describe the clinical and laboratory data and the etiology of CAD. Comparison between this case series and those described in the literature. Materials and Methods: Retrospectively, we analyzed clinical data of patients from Hospital Universitario San Vicente Fundación with positive results for cold agglutinin assays made in the hematology lab from Universidad de Antioquia. We consider patients with titers ≥ 1:64 or Coombs test positive for cold antibodies. Results: We describe clinical and laboratory findings included crioagglutinin titers of 23 cases with CAD: 6 of them with primary CAD, 4 with non-Hodgkin Lymphoma (NHL), 8 patients with CAD associated with infectious and autoimmune disease and 5 with CAD miscellaneous diseases. Discussion and Conclusions: This is the first CAD case series described in Colombia. Age and gender were like others case series. Most of patients presented with hemolityc anemia and cold related symptoms. The hemoglobin/ hematocrit ratio was 1:2. Secondary causes were vasculitis, lupus and malaria. Primary CAD were related to NHL, specifically limphoplasmocytic Most of the treatments of primary CAD included rituximab.

Childhood pneumonia: read the smear and clinch the diagnosis

Childhood pneumonia has a myriad of disease causing organisms. Identifying the etiology often helps us predict the natural course of the illness. We would like to share an interesting child with pneumonia by the hematological manifestation of the disease. Case report of this study is a 8 year old boy who presented with high grade fever for eleven days associated with cough. History of skin rashes which worsened following therapy with penicillin. On Examination child had maculopapular rashes predominantly over the trunk with decreased air entry in the left hemithorax. Chest x-ray done showed left lower lobe consolidation hence treated with cephalosporins and macrolide. Counts revealed falling trend in haemoglobin with high MCV count. Peripheral smear done showed agglutinated RBC'S and occasional nucleated RBC's. Direct Coombs test was positive. With these haematological manifestations child was diagnosed to have Mycoplasma pneumonia which was proven by positive antibodies against Mycoplasma. Child recovered completely and haematological manifestations became passive after four weeks. Cold agglutinin disease is poorly understood affecting 15% of patients with Autoimmune hemolytic anemia. Respiratory tract involvement and extrapulmonary complications manifest in 3-10% and 25% respectively. Antibodies (IgM) against the I antigen on human erythrocyte membranes appear during the course of M. pneumoniae infection and produce a cold agglutinin response. AIHA typically occurs during 2-3rd week after febrile illness with sudden onset of hemolysis which is self-remitting within 4-6 weeks. The conclusion of this study is extra-pulmonary manifestations in a child with pneumonia help in diagnosing the etiology. This in turn helps us like provide rationale management and Predict the natural course of the illness.

Clinical characteristics and treatment outcomes of primary autoimmune hemolytic anemia: a single center study from South India

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is a less recognized, potentially fatal condition. There is a scarcity of data on clinicoserological characteristics and response to therapy concerning this disease from South India. METHODS: Data for 33 patients with primary AIHA recorded from July 2009 to June 2015 were retrospectively analyzed for clinical presentation, response to frontline therapy, durability of response, time to next treatment (TTNT), and response to second-line agents. RESULTS: The median follow-up period was 50 months. Among 33 patients, 48% of the cases were warm autoimmune hemolytic anemia (WAIHA), 46% were cold agglutinin disease (CAD), and 6% were atypical. Three-fourth of patients had severe anemia (<8 g/dL hemoglobin [Hb]) at onset; younger patients (age <40 yr) had more severe anemia. All of the patients who required treatment received oral prednisolone at 1.5 mg/kg/d as a frontline therapy, and the response rate was 90% (62% complete response [CR] and 28% partial response [PR]). The overall response to corticosteroids in WAIHA and CAD was 87% and 92%, respectively. The median corticosteroid duration was 14 months, and 50% of the patients required second-line agents. Fourteen patients received azathioprine as a second-line agent, and 11 of these patients responded well, with half of them not requiring a third agent. Four patients developed severe infections (pneumonia, sepsis, and soft tissue abscess) and two had life-threatening venous thrombosis. One case of death was recorded. CONCLUSION: AIHA is a heterogeneous disease that requires care by physicians experienced in treating these patients.

Therapeutic Plasma Exchange for a Patient with Severe Cold Agglutinin Disease / 대한수혈학회지

Cold agglutinin disease is a kind of autoimmune hemolytic anemia, caused by cold agglutinin, serum autoantibodies activated at reduced body temperatures to produce red blood cell agglutination and hemolysis. In this paper we described a case of severe hemolytic anemia in a cold agglutinin disease patient treated with therapeutic plasma exchange. Therapeutic plasma exchanges were performed four times every other day. Over the same period, a total of 8 units of washed red blood cells were transfused. Then hemoglobin was increased from 4.0 g/dL to 7.8 g/dL. On the 12th hospital day hemoglobin level was decreased again to 4.2 g/dL and fludarabine chemotherapy was started on the 14th hospital day. The patient's symptoms were relieved and she was discharged on the 30th hospital day. As in this case, therapeutic plasma exchange could be considered as secondary therapy for temporary improvement of acute severe hemolytic anemia in cold agglutinin disease.

A Case of Cold Agglutinin Disease Accompanied by Bacterial Pneumonia That Was Treated with Rituximab / 대한수혈학회지

Cold agglutinin disease (CAD) is a small group of disorders that is characterized by cold-reactive autoantibodies that bind to erythrocyte carbohydrate antigens, and this causes hemagglutination and complement-mediated hemolysis. Autoimmune hemolytic anemia (AIHA) is an immune disorder that is mediated via auto-antibodies produced by lymphoid B cells against red blood cells. The disorder may be a primary (idiopathic) or secondary disease with an underlying autoimmune disease, a lymphoproliferative disorder or infection. The mainstay of initial treatment is immunosuppression with glucocorticosteroids. For those who do not have satisfactory response to initial glucocorticosteroids or they have a relapse after initially successful treatment, splenectomy or other immunosuppressive agents such as azathioprine, cyclosporine and intravenous immunoglobulin (IVIG) could be the next available options. More recently, rituximab, which is a human-murine chimeric monoclonal antibody specific for the CD20 antigen found on the surface of B lymphocytes, is also available. We report here on the successful use of rituximab for the treatment of a Korean elderly patient with CAD and the patient presented with recurrent AIHA.

Cold agglutinin disease (CAD)with autoimmune haemolytic anaemia: a case report of a coronary artery disease patient

Cold agglutinin disease (CAD) with autoimmune haemolytic anemia is characterized by the production of harmful cold autoantibodies associated with increased red cell destruction during exposure to cold. The treatment of CAD is very difficult and a great effort is required to obtain therapeutic success. Cyclophosphamide is a potent immunosuppressive agent which is widely used in all bone marrow transplantation conditioning regimens for patients with acquired severe aplastic anemia. In this report, we describe the case of a coronary artery disease patient with severe CAD, but without lymphoproliferative disease, in which general measures and immunosuppressive therapies were adopted, there by avoiding blood transfusions.

A doença por aglutininas a frio (CAD) cursando com anemia hemolítica auto-imune (AHAI) é decorrente da produção de autoanticorpos que reagem muito bem a baixas temperaturas, dirigidos contra hemácias autólogas. A habilidade desses anticorpos em destruir as hemácias encontra-se diretamente relacionada à sua capacidade em fixar complemento durante a exposição do paciente a baixas temperaturas. A AHAI por anticorpos frios pode ser idiopática - ausência de doença de base - ou secundária, geralmente associada a desordens linfoproliferativas de células B ou determinados processos infecciosos. A hemólise é intravascular, através de aglutininas da classe IgM, com teste direto da antiglobulina humana positivo para complemento. O tratamento da CAD é difícil, exigindo um esforço contínuo, necessário para se obter sucesso terapêutico. A ciclofosfamida é um agente imunossupressor potente, amplamente utilizado em transplantes de medula óssea, particularmente nos portadores de anemia aplástica. Descrevemos o caso de um coronariopata portador de CAD severa, cuja exploração diagnóstica excluiu doença linfoproliferativa. Adotamos medidas gerais de suporte e terapia imunossupressora, coibindo o uso de hemotransfusões.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

A Case of Acute Respiratory Distress Syndrome by Nosocomial Mycoplasma Pneumonia Associated with Cold Agglutinin Disease in Primary CNS Lymphoma / 감염과화학요법

Although Mycoplasma pneumonia is frequently observed in immunocompromized patient if, rarely results in acute respiratory distress syndrome (ARDS). The cold agglutinin is positive in 33-76% of patients with M. pneumonia infection. We experienced a case of ARDS due to mycoplasma pneumonia associated with cold agglutinin disease in primary CNS lymphoma. He was a 60-year old primary CNS lymphoma patient with mycoplasma pneumonia and cold agglutinin disease who rapidly progressed to ARDS after 1 cycle of chemotherapy. He completely recovered with roxithromycin, levofloxacin, and ventilator supports. After recovery 2nd cycle of combination chemotherapy and brain radiation therapy was given and, CNS lymphoma is in complete remission until now.

Cold Agglutinin Disease due to Anti-Pr Cold Autoantibody in a Patient with Bone Marrow Transplantation / 대한수혈학회지

Cold agglutinin disease (CAD) is a most common autoimmune hemolytic anemia (AIHA) induced by cold antibody. CAD represents approximately 16-32% of AIHA cases and causative cold autoantibodies commonly show specificity against the I antigen. We report a case of cold agglutinin disease with anti-Pr cold autohemolysin. A 20 year old woman with a history of bone marrow transplantation was admitted with nausea, vomiting, and pallor. Direct antiglobulin tests were positive with IgG and C3d specific AHG reagents. Cold agglutinin titer was as high as 1:1024 at 4degrees C, 1:16 at room temperature, negative at 37degrees C. The agglutinin titer was diminished after treatment with protease, ficin and immunohematologic results of cold agglutinin was compatible with anti-Pr specificity. In unexpected antibody identification test, anti-M which showed reactivity at anti-human globulin phase was identified. Washed and prewarmed 16 units of A+, M antigen negative red blood cells were transfused. After two weeks, patient was improved with steroid therapy and experienced relief of fever and hemolysis, and she was discharged.