Síndrome de Evans y embarazo: reporte de un caso / Evans syndrome and pregnancy: a case report

Resumen El síndrome de Evans es una enfermedad conformada por la presencia simultánea o secuencial de trombocitopenia inmunitaria y anemia hemolítica autoinmunitaria, que puede ser primaria o secundaria a otra patología. Es una afección poco frecuente, por lo que es necesario tener una alta sospecha, y descartar otras patologías que cursan con dichas alteraciones hematológicas, para hacer el diagnóstico. Su manejo representa un desafío terapéutico dado su curso crónico y recidivante. La presentación durante el embarazo se asocia a morbilidad materna y fetal. A continuación presentamos el caso de una gestante en quien se pesquisó trombocitopenia severa aislada al ingreso al control prenatal, y que en el curso del embarazo desarrolló AHAI conformando un síndrome de Evans, que se consideró secundario a LES incompleto al realizar el estudio reumatológico. Debido a la pobre respuesta al tratamiento médico con corticoides e inmunosupresores, la mayor parte del embarazo se mantuvo hospitalizada para observación, ajuste y cambio de terapia, siendo necesario recurrir a manejo quirúrgico con esplenectomía.

Abstract Evans syndrome is a rare entity formed by the simultaneous or sequential presence of immune thrombocytopenia and autoimmune hemolytic anemia, which can be primary or secondary to another pathology. The presentation of this disease during pregnancy is associated with maternal and fetal morbidity. The syndrome's diagnosis requires a high suspicion and the ruling out of other pathologies that can happen with the same hematological alterations. The management represents a therapeutic challenge because of its chronic and recurrent course. Below we present the case of a pregnant woman in whom isolated severe thrombocytopenia was detected at admission for prenatal control, and who developed AIHA during the pregnancy, forming Evans syndrome, which was considered secondary to incomplete SLE when performing the rheumatological study. Due to the poor response to medical treatment with corticosteroids and immunosuppressants, the patient was hospitalized for most of her pregnancy for observation, adjustment and change of therapy, and even it was necessary resort to surgical management with splenectomy.

Anemia hemolítica autoinmune por crioaglutininas y crisis aplásica en una paciente con hemoglobinopatía SC / Autoimmune hemolytic anemia with cryoagglutinins and aplastic crisis in a patient with SC hemoglobinopathy

La infección por parvovirus B19 humano, es la causa de la mayor parte de los casos de crisis aplásica transitoria que aparecen de forma brusca en pacientes con enfermedades hemolíticas crónicas, como es el caso de la drepanocitosis. Por otra parte, se han descrito unos pocos casos de infección aguda, por parvovirus B19 humano como causa de anemia hemolítica autoinmune, por medio de la formación de anticuerpos dirigidos contra los glóbulos rojos. La asociación entre drepanocitosis y anemias hemolíticas autoinmunes es poco frecuente. Se reporta un caso poco usual de una paciente adulta, con antecedentes de hemoglobinopatía S/C que presentó una crisis aplásica y posteriormente apareció una anemia hemolítica autoinmune diagnosticada en el Instituto de Hematología e Inmunología. Se trató con dosis inmunosupresoras de esteroide, con lo que se alcanzó la remisión de la anemia hemolítica autoinmune(AU)

Infection with human B19 parvovirus is the cause of most cases of transient aplastic crisis that appear in patients with chronic hemolytic diseases, as in the case of sickle cell disease. On the other hand, a few cases of acute infection by human parvovirus B19 have been described as a cause of autoimmune hemolytic anemia, through the formation of antibodies directed against red blood cells. The association between sickle cell disease and autoimmune hemolytic anemia is rare. We report an unusual case of an adult patient, with a history of S C hemoglobinopathy who presented an aplastic crisis and subsequently an autoimmune hemolytic anemia diagnosed at the Institute of Hematology and Immunology, treated with high steroids doses, reaching the remission of autoimmune hemolytic anemia and constitutes the first report in Cuba(AU)

Anticuerpos contra la cardiolipina en glomerulonefritis postestreptocócica concurrente con anemia hemolítica autoinmunitaria: a propósito de un caso / Anticardiolipin antibodies in concurrent poststreptococcal glomerulonephritis and autoimmune hemolytic anemia: A case report

En este artículo, presentamos el caso de una paciente con glomerulonefritis aguda postestreptocócica (GNAPE) y anemia hemolítica autoinmunitaria (AHAI). Además de los signos típicos de la GNAPE, la paciente tuvo un resultado positivo en la prueba de antiglobulina directa y anticuerpos contra la cardiolipina sin que presentara las manifestaciones clínicas típicas del síndrome antifosfolipídico. Este caso genera dudas respecto de la relación entre el estreptococo y el desarrollo de anemia hemolítica autoinmunitaria en los niños. Este caso destaca la posibilidad de que las infecciones estreptocócicas de nuestra paciente podrían haber causado la anemia, ya sea en el contexto de anticuerpos antifosfolipídicos preexistentes o por haber desencadenado el desarrollo de anticuerpos patogénicos, que luego lleva a la presentación clínica de hemólisis. Se presume que, en la paciente, los anticuerpos contra la cardiolipina inducidos por la infección estreptocócica podrían tener una función directa en la presentación clínica de AHAI.

We present a case of acute post-streptococcal glomerulonephritis (APSGN) with autoimmune hemolytic anemia (AIHA). Along with the classic findings of APSGN, the patient had a positive direct antiglobulin test and an anticardiolipin antibody without any typical clinical manifestations of antiphospholipid syndrome (APS). This case raises questions of the relationship between Streptococcus and the development of autoimmune hemolytic anemia in children. Our case highlights the possibility that the streptococcal infections in this patient might be responsible for her anemia, either in setting of underlying antiphospholipid antibodies, or in having triggered the development of pathogenic antibodies, which subsequently leads to the clinical evolution of hemolysis. It is presumed that in our case, the anticardiolipin antibody induced by streptococcal infection may play a direct role in the clinical evolution of AIHA.

Síndrome de aglutininas frías y púrpura trombocitopénica autoinmune: Un caso inusual de síndrome de Evans / Cold agglutinins syndrome and autoimmune thrombocytopenic purpura: An unusual case of Evans syndrome

El síndrome de Evans es un trastorno poco frecuente en el que se observan trombocitopenia y anemia, ambas de etiología autoinmune; las que pueden ocurrir de manera simultánea o sucesiva. Se presenta un caso poco usual de anemia hemolítica autoinmune por anticuerpos fríos asociada a púrpura trombocitopénica autoinmune. Paciente femenina de 22 años de edad con diagnóstico de púrpura trombocitopénica autoinmune, después de 7 años de evolución y un año en remisión, presentó una anemia hemolítica autoinmune por anticuerpos fríos, refractaria al tratamiento con esteroides y alcaloides de la Vinca, que requirió transfusiones de concentrado de eritrocitos y logró la remisión con la administración de anticuerpo monoclonal anti CD 20. Los restantes estudios de autoinmunidad fueron negativos. Actualmente se mantiene asintomática y sin tratamiento inmunosupresor(AU)

Evans syndrome is a rare disorder in which thrombocytopenia and anemia are observed, both of autoimmune aetiology, which may occur simultaneously or successively. A rare case of cold autoimmune hemolytic anemia associated to autoimmune thrombocytopenic purpura is presented. A 22-year-old female patient with diagnosis of autoimmune thrombocytopenic purpura, after 7 years of evolution and one year in remission, has a cold autoimmune hemolytic anemia, refractory to steroid treatment and vinca alkaloids, which requires transfusions of packed erythrocytes and achieves remission with anti CD 20 monoclonal antibody. The remaining studies of autoimmunity are negative. Currently the patient is asymptomatic and without immunosuppressive therapy(AU)

Pure red-cell aplasia and autoimmune hemolytic anemia in a patient with acute hepatitis A

Pure red cell aplasia (PRCA) and autoimmune hemolytic anemia (AIHA) have rarely been reported as an extrahepatic manifestation of acute hepatitis A (AHA). We report herein a case of AHA complicated by both PRCA and AIHA. A 49-year-old female with a diagnosis of AHA presented with severe anemia (hemoglobin level, 6.9 g/dL) during her clinical course. A diagnostic workup revealed AIHA and PRCA as the cause of the anemia. The patient was treated with an initial transfusion and corticosteroid therapy. Her anemia and liver function test were completely recovered by 9 months after the initial presentation. We review the clinical features and therapeutic strategies for this rare case of extrahepatic manifestation of AHA.

Concentración de autoanticuerpos IgG en hematíes y respuesta al tratamiento en la anemia hemolítica autoinmune / Concentration of IgG autoantibodies on red blood cells and response to treatment in autoimmune hemolytic anemia

Introducción: no existen suficientes evidencias que relacionen la respuesta al tratamiento con el patrón de autoanticuerpos o su concentración en los hematíesde los pacientes con anemia hemolítica autoinmune. Objetivo: en este trabajo se investigó la asociación entre la respuesta al tratamiento y la remisión de la enfermedad con la concentración de autoanticuerpos IgG en los hematíes al inicio de la enfermedad. Métodos: se realizó un estudio retrospectivo de 44 pacientes adultos con anemia hemolitica autoinmune caliente idiopática por presencia únicamente de autoanticuerpos IgG donde se relacionó la respuesta al tratamiento con el patrón de inmunoproteínas en los hematíes, la concentración de autoanticuerpos IgG en los hematíes, las cifras de hemoglobina y el conteo de reticulocitos. Resultados: no se observó asociación entre el patrón de inmunoproteínas en los hematíes, las cifras de hemoglobina, el conteo de reticulocitos y la cuantificación de IgG en los hematíes, con la respuesta al tratamiento con prednisona, la administración de tratamiento de segunda línea ni con la remisión de la enfermedad, aunque el número de moléculas de IgG por hematíe fue 1,4 veces superior en los pacientes sin remisión en relación con los casos con remisión de la enfermedad. Conclusiones: el patrón de inmunoproteínas en los hematíes, las cifras de hemoglobina, el conteo de reticulocitos y la cuantificación de IgG en los hematíes al inicio de la enfermedad, no es un marcador pronóstico de respuesta al tratamiento

Introduction: there is not enough evidence that relates the response to treatment with the pattern of autoantibodies or their concentration on red blood cells in patients with autoimmune hemolytic anemia. Objective: to investigate the association of the response to treatment and the remission of the disease with the concentration of IgG autoantibodies on red blood cells at the beginning of the disease. Methods: a retrospective study in 44 adult patients with idiopathic warm autoimmune hemolytic anemia with only IgG autoantibodies was carried out in order to relate the response to treatment to the immunoprotein pattern of red blood cells, the IgG autoantibodies concentration on red blood cells, the hemoglobin level and the reticulocyte count. Results: association was not observed between the immunoprotein pattern, the hemoglobin level, the reticulocyte count and the quantitation of IgG on red blood cells, with the response to treatment with prednisone, administration of second-line treatment and the remission of the disease; although, the number of IgG molecules on red blood cells was 1,4 times higher in patients with no remission of the disease to those with remission. Conclusions: the immunoprotein pattern, the hemoglobin level, the reticulocyte count and the quantitation of IgG on red blood cells at the beginning of the disease are not a prognostic marker of the response to treatment

Anemia hemolítica autoinmune en un niño con hepatitis de células gigantes / Autoimmune hemolytic anemia in an infant with giant cell hepatitis

La asociación de anemia hemolítica autoinmune (AHAI) con hepatitis de células gigantes (HCG) es un transtorno raro en la infancia. Son pocos los casos reportados y la gran mayoría fallecen a pesar de transplante hepático. La AHAI usualmente precede el desarrollo de la afección hepática. El diagnóstico temprano de esta asociación y el inicio de terapia inmunosupresora previene la progresión de la enfermedad...

Caracterización de los autoanticuerpos en la anemia hemolítica autoinmune secundaria al tratamiento con interferón alfa / Characterization of autoantibodies in autoimmune hemolytic anemia following treatment with interferon alfa

Se estudiaron 13 pacientes con leucemia mieloide crónica y anemia hemolítica autoinmune inducida por el interferón alfa, a quienes se les realizó la detección de inmunoproteínas y la caracterización de las subclases de IgG en los hematíes mediante la prueba de antiglobulina directa (PAD) y la técnica de microplacas. Se aplicó además un ELISA para la cuantificación de inmunoglobulinas en los hematíes. Se detectó la presencia de IgG y C3 en el 53,84 por ciento de los casos, IgG sola en el 23,07 por ciento y en el 15,38 por ciento se identificaron autoanticuerpos IgG e IgA. En 11 pacientes se demostró la presencia de IgG1 y en un caso se identificaron además autoanticuerpos de la subclase IgG3. El ELISA detectó autoanticuerpos en concentraciones de 183 moléculas de IgG por hematíe en un paciente con PAD negativa. En los pacientes con hemólisis de alto grado se encontró una concentración de autoanticuerpos entre 1 500 y 3 180 moléculas de IgG por hematíe, mientras que en los casos con hemólisis de bajo grado se comportó entre 183 y 1 000 moléculas. Se observó una correlación negativa entre las cifras de Hb y los valores de haptoglobina plasmática con el número de moléculas de IgG por hematíe y una correlación positiva entre este último con el conteo de reticulocitos

We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 percent of cases, IgG alone in 23.07 percent and in 15.38 percent were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count

Livedo reticular associado com Anemia Hemolítica Autoimune: remissão prolongada induzida pelo Transplante de Células-Tronco do Sangue Periférico com recaída após 10 anos e restauração dos níveis de hemoglobina por rituximabe / Livedo reticularis associated with autoimmune hemolytic anemia: prolonged remission induced by peripheral blood stem cell transplantation relapse after 10 years and restoration of hemoglobin levels by rituximab

A anemia hemolítica autoimune (AHAI) é uma doença na qual são produzidos anticorpos diretamente contra as glicoproteínas adsorvidas na superfície da membrana dos eritrócitos. Algumas medicações e outras associações têm sido implicadas. Descrevemos e discutimos um caso de livedo reticular associado à AHAI tratado com transplante de células-tronco de sangue periférico (TCTSP) e que entrou em total remissão por 10 anos. Após esse período, a paciente apresentou recaída, foi tratada com anticorpo anti-CD20 (rituximabe), e atualmente encontra-se em total remissão. O papel do TCTSP e o uso de rituximabe no tratamento de AHAI serão discutidos neste relato de caso.

Autoimmune hemolytic anemia (AIHA) is a disease where patients produce antibodies against erythrocytes directed towards membrane glycoproteins adsorbed onto the erythrocyte surface. Drugs and other associations have been implicated. It is described and discussed a case of livedo reticularis associated with AIHA treated with peripheral blood stem cell transplantation (PBSCT) that went into full remission for 10 years. After that period the patient relapsed and was treated with antibody anti-CD20, rituximab, and is now in full remission. The role of PBSCT and rituximab in the treatment of AIHA will be discussed.

Síndrome de Evans de aparición súbita en el embarazo / Evans syndrome of sudden onset in pregnancy

La trombocitopenia complica hasta el 10 por ciento de los embarazos. El síndrome de Evans es la coexistencia de la trombocitopenia inmune con anemia hemolítica autoinmune. Se presenta un caso de síndrome de Evans durante el embarazo, complicado por preclampsia y neutropenia fetal. Una mujer de 20 años de edad, previamente sana, primigesta, que presentó a las 34 semanas de gestación dolor epigástrico, trombocitopenia y pre eclampsia. Se le realizó parto por cesárea, por presentar síndrome de HELLP. A los 25 días de postparto, reingresó al Hospital con trombicitopenia severa, plaquetas 2000 x mm3 , anemia hemoglobina 5,3g/dl y fiebre. El Coombs directo fue positivo y el análisis posterior demostró la presencia de anticuerpos anti-plaquetarios, y anticardiolipina. Recibió transfusiones de sangre y plaquetas. Se le trató con prednisona, plasmaferesis, azatioprima y finalmente, resolvió su cuadro clínico después de 10 días de internamiento en una unidad de cuidado intensivo.

[Pyoderma gangrenosum in a patient with autoimmune haemolytic anemia]

Pyoderma gangrenosum [PG] is an uncommon, non-infectous, neutrophilic, ulcerative disease with typically starts with pustules which rapidly evolve to painful ulcers with undermined violaceous borders. The diagnosis of PG is based on clinical features and requires exculusion of other conditions that produce ulcerations. PG is associated with a variety of systemic diseases that the most commonly of them is include inflammatory bowel diseases, leukaemia, myeloma, monoclonal gammopathies, chronic active hepatitis, systemic lupus erythmatous and arthritis. Two cases of PG with haemolytic anemia have been reported and this patient is third one. Patient was a 19-year-old girls, with haemolytic anemia from 15 years ago. Who was referred with an ulcer, 2x3 cm in diameter, on her lower right leg with violaceous border and on her lower left leg with painful haemorrhagic bulla 4x6 cm in diameter. Because, PG in many cases is associated with an underlying disease in these patients, search for finding possible underlying diseases is necessary

Clinical course of autoimmune hemolytic anemia: an observational study

OBJECTIVE: Autoimmune hemolytic anemia is characterized by the production of autoantibodies against erythrocyte membrane antigens. This study was carried out to identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG) Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS: We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS: The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients), followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkin's lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months). Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION: Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

Autoimmune hemolytic anemia complicating disseminated childhood tuberculosis.

An 8-year-old girl presented with severe autoimmune hemolytic anemia (AIHA) in association with mediastinal widening. Biopsy of mediastinal lymph node confirmed the diagnosis of tuberculosis. A diagnosis of disseminated tuberculosis in association with AIHA was made, and the patient was treated with steroids and antitubercular therapy. This is the first report case of AIHA in association with childhood tuberculosis; we also discuss other reported cases of AIHA in association with adult tuberculosis in English literature.

Myelopathy during treatment of autoimmune hemolytic anaemia.

A specific neurological syndrome resembling, subacute combined degeneration of spinal cord, has been observed to occur during treatment of autoimmune hemolytic anaemia (AHA). We propose that folate administration can precipitate this neurological syndrome in patients with subclinical deficiency of vitamin B12, a phenomenon more likely to occur in tropical countries. Such cases have not been previously reported.

Linear scleroderma and autoimmune hemolytic anaemia.

Coexistence of localized scleroderma with other autoimmune disorders is not seen frequently. It has been reported to occur with myasthenia gravis, hemiatrophy and systemic lupus erythematosus. In this report we describe an association wherein linear scleroderma coexisted with autoimmune haemolytic anaemia.