[Cold agglutinin syndrome associated with infectious mononucleosis: A case report]. / Síndrome por aglutininas frías secundario a mononucleosis infecciosa: reporte de un caso.

Background: Cold agglutinin syndrome (CAS) is a hemolytic anemia mediated by antibodies, mainly IgM, whose maximum activity occurs at 4 °C. It happens secondary to infectious, autoimmune or neoplastic diseases, due to the formation of antibodies that cross-react against erythrocyte antigens, particularly of the I system. Here, we describe a case of CAS associated to Epstein-Barr virus (EBV) reactivation in a patient with primary human immunodeficiency virus (HIV) infection. Clinical case: 22-year old man with no medical history, hospitalized due to mononucleosis and anemic syndrome. Hemoglobin of 3.7 g/dL and elevation of lactate dehydrogenase were documented. In the peripheral blood smear it was observed spherocytosis, polychromasia and nucleated erythrocytes. EBV infection was confirmed with serology and viral load, as well as seronegative HIV infection with positive viral load. The C3d monospecific direct antiglobulin test was positive and an irregular antibody screening revealed the presence of an anti-I antibody. The patient received transfusion support and conservative treatment, with remission of the symptoms 2 weeks after admission. Conclusions: Cold agglutinin syndrome is a rare, potentially fatal complication of infectious mononucleosis, which should be considered in the face of findings suggestive of hemolysis in order to initiate support measures in a timely manner.

Introducción: el síndrome por aglutininas frías (SAF) es una anemia hemolítica mediada por anticuerpos principalmente de tipo IgM, cuya máxima actividad se da a 4 °C. Se presenta en el contexto de enfermedades infecciosas, autoinmunes o neoplásicas por la formación de anticuerpos que tienen reacción cruzada contra antígenos eritrocitarios, particularmente del sistema I. En este trabajo presentamos un caso de SAF asociado a reactivación del virus de Epstein-Barr (VEB) en un paciente con primoinfección por el virus de la inmunodeficiencia humana (VIH). Caso clínico: hombre de 22 años, sin antecedentes patológicos, hospitalizado por síndrome mononucleósico y anémico. Presentó hemoglobina de 3.7 g/dL y elevación de lactato deshidrogenasa. En el frotis de sangre periférica se observó esferocitosis, policromasia y eritrocitos nucleados. Se confirmó infección por VEB con serología y carga viral, así como infección por VIH seronegativa, con carga viral positiva. La prueba de antiglobulina directa monoespecífica a C3d fue positiva y el rastreo de anticuerpos irregulares demostró un anticuerpo anti-I. El paciente recibió soporte transfusional y tratamiento conservador, con remisión del cuadro a las 2 semanas de su ingreso. Conclusiones: el SAF es una complicación poco frecuente de la mononucleosis infecciosa, potencialmente mortal, la cual debe ser considerada ante hallazgos sugestivos de hemólisis con la finalidad de iniciar medidas de soporte de forma oportuna.

Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.

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 imunomediada medicamentosa em uma cadela / Immune-mediated hemolytic anemia in a bitch triggered by drugs

Background: Immune-mediated hemolytic anemia (IMHA) is characterized by an autoimmune response with production of auto-antibodies and destruction of erythrocytes resulting in anemia. Primary IMHA is referred to a condition when the cause is unknown (idiopathic), whereas secondary IMHA involves changes in red blood cells caused by the action of drugs, neoplasms, or infectious diseases. The diagnosis can be made through changes in the blood count, usually of a regenerative character, Coombs test, and autoagglutination test. The present study aimed to report a case of drug-induced hemolytic anemia, with emphasis on the clinical signs, diagnostic methods, and treatment, in a female dog. Case: A 9-year-old mixed-breed bitch weighing 29.6 kg was referred to the Veterinary Medical Teaching Hospital (HCVUFRGS) with a previous diagnosis of gallbladder mucocele that was unresponsive to clinical treatment. After laboratory tests, cholecystectomy was performed, and the procedure required conversion from laparoscopic to open cholecystectomy. Therapy included administration of amoxicillin, dipyrone, tramadol hydrochloride, and meloxicam. Three days after surgery, the dog presented with apathy, lethargy, hyporexia, and a pale and subicteric mucosa. The patient developed hypochromic macrocytic anemia with reticulocytosis, spherocytosis, anisocytosis, and leukocytosis with neutrophilia. The result of the autoagglutination test was positive, confirming the diagnosis. All medications were suspended, and immunosuppressive treatment with dexamethasone was included, with a subsequent switch to prednisolone. After 10 days of treatment, the patient experienced significant improvement, and therapy was discontinued. Discussion: Based on the patient's history, the cause of the IMHA was secondary to drug administration, and it is not possible to distinguish if it was due to one or a combination of drugs, as they were all started and stopped simultaneously. The patient had hypothyroidism, which may have contributed to the production of antibodies against TSH receptors, blocking the hormone's action, thereby causing tissue damage due to T cell-mediated cytotoxicity and the effect of cytokines. The pale and subicteric mucosa, apathy, weakness, lethargy, exercise intolerance, and dyspnea resulted from extravascular hemolysis and bilirubin released from erythrocyte rupture with a subsequent decrease in the number of red blood cells, leading to oxygen transport deficiency. The diagnosis is based on the blood count and results of autoagglutination supported by the response to immunosuppressive therapy. Anemia results in increased production and release of precursor cells from the bone marrow, accompanied by reticulocytosis and increased mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). The treatment of IMHA consists of supportive care and immunosuppressive therapy with corticosteroids to ensure suppression of the immune system, preventing response against erythrocytes. Initially, tramadol hydrochloride, dipyrone, and amoxicillin with potassium clavulanate were suspended to interrupt the cause of IMHA, and administration of dexamethasone in an immunosuppressive dose was started. Therefore, it is important to include drug-induced IMHA in the differential diagnosis of patients who present with anemia after using medications. Early diagnosis, initiation of therapy, and adequate care were important factors for the recovery of the animal.

[Autoimmune hemolytic anemia. Review of 43 cases]. / Anemia hemolítica autoinmune en Chile: un análisis retrospectivo de 43 pacientes.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is an uncommon disease. In its presentation, it can be severe and even lethal. There is only one clinical report concerning this pathology in Chile. OBJECTIVE: To describe the clinical characteristics and evolution of adult AIHA inpatients. MATERIALS AND METHODS: Retrospective review of clinical records of adult AIHA inpatients between January 2010 and June 2018 was done. Demographic, clinical, laboratory and therapeutic information was analyzed. A descriptive, analytical and survival analysis was performed. RESULTS: Forty-three adult patients diagnosed with AHIA were hospitalized in a period of 8 years. Median age was 63 years (range 22-86 years), mostly women (72%). Warm antibodies were detected in 36 cases (84%) and cold antibodies in seven. Seventy two percent of the patients had an underlying cause, and 58% were secondary to lymphoproliferative neoplasms. All patients except two, received steroids as initial treatment, with response in 37 (90%) of them. Three refractory patients received rituximab, with response in all of them, and relapse in one. Median follow-up was 38 months (range 2-98 months). Five year overall survival was 72%. CONCLUSION: AHIA in adults inpatients is a heterogeneous disease, mainly due to warm antibodies, and to secondary etiology.

Anemia hemolítica autoinmune en Chile: un análisis retrospectivo de 43 pacientes / Autoimmune hemolytic anemia: review of 43 cases

Background: Autoimmune hemolytic anemia (AIHA) is an uncommon disease. In its presentation, it can be severe and even lethal. There is only one clinical report concerning this pathology in Chile. Objective: To describe the clinical characteristics and evolution of adult AIHA inpatients. Materials and Methods: Retrospective review of clinical records of adult AIHA inpatients between January 2010 and June 2018 was done. Demographic, clinical, laboratory and therapeutic information was analyzed. A descriptive, analytical and survival analysis was performed. Results: Forty-three adult patients diagnosed with AHIA were hospitalized in a period of 8 years. Median age was 63 years (range 22-86 years), mostly women (72%). Warm antibodies were detected in 36 cases (84%) and cold antibodies in seven. Seventy two percent of the patients had an underlying cause, and 58% were secondary to lymphoproliferative neoplasms. All patients except two, received steroids as initial treatment, with response in 37 (90%) of them. Three refractory patients received rituximab, with response in all of them, and relapse in one. Median follow-up was 38 months (range 2-98 months). Five year overall survival was 72%. Conclusion: AHIA in adults inpatients is a heterogeneous disease, mainly due to warm antibodies, and to secondary etiology.

Health-Related Quality of Life and Behavioral Functioning after Intrauterine Transfusion for Alloimmune Anemia.

OBJECTIVE: To assess health-related quality of life (HRQOL) and behavioral functioning in children and adolescents treated before birth with intrauterine intravascular blood transfusion for alloimmune anemia. STUDY DESIGN: Cross-sectional cohort study conducted at the Dutch referral center for the management of fetal alloimmune anemia. Follow-up data were available for 285 children at a mean age of 10.5 years (range, 3-21.5 years) with a response rate for questionnaires of 97%. Child-, adolescent-, and parent-rated HRQOL was evaluated with The Netherlands Organization for Applied Scientific Research Child/Adult Quality of Life Questionnaire (TACQOL/TAAQOL). Parents reported on behavioral functioning with the Strengths and Difficulties Questionnaire. Scores were compared with Dutch norm data. RESULTS: Significantly lower scores were reported by parents of children 6-11 years of age compared with Dutch norms on 3 scales: cognitive functioning, social functioning, and positive emotions (P < .00, P = .02, and P = .04). In children aged 8-11 years only the cognitive functioning scale score was significantly lower compared with Dutch norms (P = .01). The children aged 12-15 years reported higher scores on the negative emotions scale (P = .02). When corrected for multiple testing, only the parent-rated cognitive functioning scale remained significant (P < .001). Regarding the HRQOL scores of adolescents aged ≥16 years, no differences were detected. Overall, behavioral difficulties were reported in 37/246 (15%) children aged 3-16 years, and were associated with maternal educational levels (P < .001). CONCLUSION: Parents reported lower scores on cognitive functioning in their children aged 6-11 years compared with norms. Behavioral difficulties were more prevalent than norms, and were associated with maternal educational level. Outcomes of children after intrauterine intravascular blood transfusion were quite good overall.

Síndrome de Evans Fisher / Evans Fisher Syndrome

El síndrome de Evans Fisher fue descrito en 1951 por Robert Evans, definido como un trastorno inmunológico atípico y poco frecuente causado por anticuerpos contra antígeno de membrana, de hematíes y plaquetas cursando con manifestaciones hemorrágicas en piel y mucosas generalmente de evolución no siempre favorable, con tendencia a la cronicidad y frecuentes remisiones. Se presentó un paciente cuyo diagnóstico se realizó al determinar la presencia de anticuerpos contra las células sanguíneas antes mencionadas en la infancia (a los 9 meses) con una evolución desfavorable que la llevó a varios ingresos en cuidados intensivos, ahora con 15 años y 11 semanas de gestación. Cursó con episodios importantes de hemólisis, el tratamiento esteroideo no fue efectivo y fue necesario de la hemoterapia ir a la interrupción de la gestación en aras de preservar la vida de la madre.(AU)

Evans Fisher Syndrome was described in 1951 by Robert Evans, defined as an atypical immune disorder and infrequent caused by antibodies against membrane antigen of red cells and platelets with hemorrhagic manifestations in skin and mucous membranes, generally evolving not always favorable prone chronicity and frequent referrals. A patient whose diagnosis was made to determine the presence of antibodies against blood cells mentioned before in childhood (at 9 months) with an unfavorable evolution that led to several admissions at intensive care. Now the patient is 15 years and has 11 weeks of gestation and presented important episodes of hemolysis, steroid treatment was not effective so to interrupt the pregnancy was necessary in order to preserve the life of the mother.(AU)

Tratamiento de las anemias hemolíticas autoinmunes / Treatment of autoimmune hemolytic anemias

El tratamiento de las anemias hemolíticas autoinmunes (AHAI) se basa en la evaluación clínica individual, las características inmunoquímicas de los anticuerpos que las generan y su carácter idiopático o secundario. El tratamiento de las AHAI primarias varía de acuerdo con su clasificación inmunohematológica; en las generadas por anticuerpos calientes el tratamiento de primera línea son los esteroides. Después de la remisión inicial, se disminuye lentamente la dosis hasta alcanzar la de mantenimiento requerida; en los pacientes corticorresistentes y corticodependientes suele emplearse la esplenectomía y el Rituximab (anticuerpo monoclonal anti CD 20), y en menor medida, algunas drogas inmunosupresoras como la azatioprina o la ciclofosfamida. Los pacientes con AHAI por aglutininas frías son refractarios al tratamiento con esteroides y la esplenectomía; los que presentan anemia estable poco sintomática suelen requerir como único tratamiento evitar la exposición al frío, y de requerir tratamiento adicional, el más efectivo es el Rituximab, aunque también se pueden emplear inmunosupresores como la ciclofosfamida y el clorambucil. La hemoglobinuria paroxística a frío generalmente no requiere tratamiento. Las AHAI mixtas se tratan de forma similar a las calientes, mientras que las secundarias a drogas suelen responder satisfactoriamente a la suspensión de la droga y al tratamiento con esteroides. En todos los tipos de AHAI deben evitarse las transfusiones de sangre, excepto cuando hay peligro para la vida, en cuyos casos deben administrarse pequeños volúmenes de concentrados de eritrocitos, en infusión lenta y a 37(0) C a los pacientes con anticuerpos fríos

The treatment of autoimmune hemolytic anemias (AIHA) is based on the individual clinical evaluation, immunochemical characteristics of the involved antibodies and the absence or presence of an underlying condition. The treatment of AIHAs varies according to its immunohematological classification. The steroids are the first line therapy for AIHA due to warm antibodies (wAIHA). After the initial remission, the doses should be reduced slowly, until the required maintenance level is reached; steroid-dependent or steroid resistant patients often require splenectomy or treatment with Rituximab (anti CD20 monoclonal antibody) and with less frequency, immunosuppressive drugs as azathioprine or cyclophosphamide. Patients with cold AIHA agglutinins (cAHAI) are resistant to steroids and splenectomy; patients with asymptomatic or stable anemia do not require treatment. Rituximab is the most effective treatment for symptomatic cases, although immunosuppressants such as cyclophosphamide and chlorambucil could be used. Paroxysmal cold hemoglobinuria do not usually require treatment. Mixed type AIHAs may be treated similarly to those with wAIHA. Drug induced AIHAs usually respond to discontinuing the offending drug and steroids treatment. Transfusion should be avoided in AIHAs, except in life threatening situations; if it is required, small volumes of erytrhocyte concentrates should be administered, slowly, in cAIHA; the blood should be prewarmed at 37(0) C

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(AU)

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(AU)

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

Simultaneous romiplostin, eltrombopag, and prednisone were successful in severe thrombocytopenia of Evans syndrome refractory to hydrocortisone, splenectomy, intravenous IgG, and rituximab.

A 58-year-old woman presented with rheumatoid arthritis-associated Evans syndrome (simultaneous autoimmune hemolytic anemia and autoimmune thrombocytopenic purpura); she was treated unsuccessfully with steroids, romiplostin, rituximab, immunoglobulin G, and splenectomy. The platelet count responded to the combined use of prednisone, eltrombopag, and romiplostin. It may be more reasonable to use combined treatments than sequential monotherapies.

Giant cell hepatitis with autoimmune hemolytic anemia in early childhood: long-term outcome in 16 children.

OBJECTIVE: To assess the outcome of giant cell hepatitis combined with autoimmune hemolytic anemia in early childhood. STUDY DESIGN: We report on 16 children with this disease evaluated over a 28-year period. RESULTS: Children (nine boys; median age, 6 months) presented with jaundice, hepatomegaly, elevated aminotransferases, a positive Coombs test, and diffuse giant-cell transformation of hepatocytes on histology. Treatment with prednisone and azathioprine, plus, in three children, cyclosporine, resulted in complete remission in eight, partial remission in six, and failure in two. Relapses of hepatitis and/or anemia occurred in 11 and 10 children, respectively, requiring prolonged high levels of immunosuppression, and splenectomy or Rituximab, respectively. Treatment was stopped after a mean duration of 6 years, with no relapse, in seven children, with a median follow-up of 14 years. One child is alive 9 years after liver transplantation. Four children died of sepsis or multiple organ failure. CONCLUSIONS: Giant cell hepatitis combined with autoimmune hemolytic anemia requires rigorous treatment. Immunosuppressive therapy results in remission in most cases. A complete cure can be expected after several years of intensive treatment. Liver transplantation may be associated with prolonged survival.

Warm autoimmune hemolytic anemia: recent progress in understanding the immunobiology and the treatment.

Autoimmune hemolytic anemia (AIHA) is defined as a condition associated with the increased destruction of red blood cells (RBCs) associated with the presence of IgG anti-RBC autoantibodies. The etiology underlying the pathogenesis of such autoantibodies is still uncertain. In the present article, we will discuss the postulated mechanisms that produce a breakdown of immunologic tolerance leading to warm AIHA including the possible roles of RBC autoantigens and the complement system, the lack of effective presentation of autoantigens, functional abnormalities of B and T cells resulting in polyclonal lymphocyte activation and alteration of cytokine production, and the role of immunoregulatory T cells. Because warm AIHA is a relatively rare clinical entity, current recommended therapeutic strategies for patients with warm AIHA are mainly based on results from small cohort studies. Clinicians must also balance the risk of withholding RBC transfusions against the possible benefit of ameliorating the hemoglobin level with such transfusions particularly in critically ill patients with warm AIHA. Glucocorticoids are the first-line treatment for patients with warm AIHA resulting in an 80% clinical response after 3 weeks of treatment. The latter, however, also may cause adverse events such as excessive weight gain, neuropsychiatric disorders, endocrine, or cardiovascular events. Splenectomy should be considered for patients who do not show a satisfactory response to glucocorticoids and may offer a success rate of up to 70% in patients with idiopathic warm AIHA. Rituximab treatment in patients with refractory warm AIHA has been well tolerated with an overall median response rate of approximately 60%. Danazol, intravenous immunoglobulin, alemtuzumab, as well as other immunosuppressive drugs have also been successfully used in patients with warm AIHA, refractory to glucocorticoids, splenectomy, and rituximab.

A life-threatening case of autoimmune hemolytic anemia successfully treated by plasma-exchange.

A case of severe AIHA caused by pan-agglutinant IgG-class antibodies was resolved with therapeutic plasma exchange, transfusions and steroids to maintain acceptable hemoglobin levels, remove free hemoglobin, reduce the title of autoantibodies and sustain cardiopulmonary functions.