Thrombotic microangiopathy in patients with sickle cell disease / Microangiopatia trombótica em pacientes com doença falciforme

ABSTRACT Objective: To describe two cases of patients who had thrombotic microangiopathy (TMA) associated with sickle cell disease (SCD). Case description: Both patients started with a painful crisis and had acute chest syndrome during hospitalization. They showed significant worsening of hemolytic anemia, with very high levels of lactate dehydrogenase, thrombocytopenia, lowered level of consciousness, organ damage and the presence of schistocytes in peripheral blood. Due to the possibility of TMA, despite the very rare association with SCD, they were treated with fresh frozen plasma replacement and plasmapheresis, with good response. Comments: TMA is a serious, life-threatening disease, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage. The association of SCD and TMA is difficult to diagnose, since they can share a similar clinical presentation. Recognizing this association and promptly instituting treatment may impact the survival of these patients.

RESUMO Objetivo: Descrever dois casos de pacientes que apresentaram microangiopatia trombótica (MAT) associada à doença falciforme (DF). Descrição do caso: Ambos os pacientes iniciaram com crise dolorosa e apresentaram síndrome torácica aguda durante a internação. Eles apresentaram piora significativa da anemia hemolítica, com níveis muito elevados de lactato desidrogenase, trombocitopenia, rebaixamento do nível de consciência, lesão de órgãos e presença de esquistócitos no sangue periférico. Diante da possibilidade de MAT, apesar da associação muito rara com DF, eles foram tratados com reposição de plasma fresco congelado e plasmaférese, com boa resposta. Comentários: A MAT é uma doença grave e com risco de vida, caracterizada por anemia hemolítica microangiopática, trombocitopenia e danos a órgãos. A associação de DF e MAT é de difícil diagnóstico, pois as duas podem ter apresentação clínica semelhante, portanto reconhecer essa associação e instituir o tratamento prontamente pode ter grande impacto na sobrevida desses pacientes.

Diferencias en los resultados quirúrgicos en pacientes con anemia preoperatoria tratada con hierro o sin hierro previo a la cirugía / Differences in surgical results for patients with pre-operative anemia treated with or without iron before surgery

Objetivos: conocer las diferencias en los resultados quirúrgicos en pacientes con anemia preoperatoria tratada con hierro carboximaltosa (HC) o sin hierro previo a la cirugía.Métodos: estudio observacional retrospectivo de dos cohortes de pacientes. Grupo sin HC preoperatorio (antes de la implementación del programa de Prehabilitación Quirúrgica) y grupo con HC (posterior a la implementación del programa). Revisión de historias clínicas electrónicas. Variables de resultado: número de transfusiones de hemoderivados necesarias después de la cirugía, complicaciones posquirúrgicas y días de estancia hospitalaria. Comparación de variables de estudio mediante prueba Chi cuadrado y t de Student. Programa estadístico SPSS v.26.Resultados: se incluyeron 152 pacientes, 92 del grupo HC (2020-2022) y 56 del grupo sin HC (2019). El 60,5% (n= 92) fue mujer. Edad media (desviación estándar) de 63,91 (13) años. Las cirugías incluidas fueron: colectomía (n= 77; 64,5%), mastectomía (n= 55; 23%) e histerectomía (n= 20; 12,5%). Se encontraron resultados estadísticamente significativos entre la necesidad de transfusiones sanguíneas (p< 0,001; OR 15,91 [4,44-57,01]), las complicaciones posoperatorias (p< 0,001; OR 7,36 [3,35-16,16]), y la estancia media hospitalaria (p< 0,001), que fue de 4,14 días en el grupo HC frente a nueve días en el grupo control sin HC.Conclusiones: el tratamiento con HC reduce el número de transfusiones sanguíneas, las complicaciones posquirúrgicas y los días de estancia hospitalaria. (AU)

Objectives: to understand the differences in surgical results in patients with preoperative anemia treated with Ferric carboxymaltose (FCM) or without iron before surgery.Methods: a retrospective observational study of two patient cohorts: a Group without preoperative FCM (before the implementation of the Surgical Prehabilitation program), and a Group with FCM (after the implementation of the program). A review of electronic clinical records; the outcome variables were the number of transfusions of blood products required after surgery, postsurgical complications, and days of hospital stay. There was a comparison of study variables through Chi square and Student’s t tests; the SPSS statistical program, v. 26, was used.Results: the study included 152 patients, 92 in the FCM Group (2020-2022) and 56 in the Group without FCM (2019); 60.5% (n= 92) were female. Their mean age (standard deviation) was 63.91 (13) years. The surgical procedures included were: colectomy (n= 77; 64.5%), mastectomy (n= 55; 23%) and hysterectomy (n= 20; 12.5%). Statistically significant outcomes were found between the need for blood transfusions (p< 0.001; OR 15.91 (4.44-57.01)), postsurgical complications (p< 0.001; OR 7.36 (3.35-16.16)), and the mean hospital stay (p< 0.001), which was 4.14 days in the FCM group vs. nine days in the control group without FCM.Conclusions: treatment with FCM reduced the number of blood transfusions, postsurgical complications, and days of hospital stay. (AU)

An atypical case of refractory passenger lymphocyte syndrome after renal transplantation / Un caso atípico de síndrome de linfocitos pasajeros refractarios después del trasplante renal

Background Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited. Case presentation A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA. Conclusion PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss (AU)

Antecedentes El síndrome de linfocitos pasajeros (PLS) causa hemólisis inmunomediada en receptores de trasplantes sólidos y de médula ósea. Los anticuerpos derivados del donante contra el eritrocito receptor impulsan la patogénesis. Es una entidad rara en el trasplante de riñón y la mayoría de los casos son autolimitados. Presentación del caso Una mujer de 36 años presentó fatiga 13 días después del trasplante renal de donante vivo. La operación transcurrió sin incidentes y fue dada de alta con las funciones normales del injerto el día 11 del trasplante. Los hallazgos coincidían con la enfermedad por crioaglutininas en el momento de su ingreso. Sin embargo, la prueba de crioaglutininas fue negativa. Finalmente, le diagnosticaron PLS. La paciente también presentó hemólisis intravascular refractaria y hemoglobinuria franca. La hemólisis fue resistente a los esteroides, la inmunoglobulina intravenosa (IgIV) y el rituximab. Debido a la anemia potencialmente mortal relacionada con PLS refractario, se interrumpieron el micofenolato y el tacrolimus. Sin embargo, persistió la hemólisis. A continuación, se obtuvo el tratamiento de inmunoadsorción (IA). Desafortunadamente, la pérdida del injerto ocurrió debido al rechazo a pesar de la resolución de PLS después de la IA. Conclusión El PLS es una entidad rara y generalmente autolimitada. Nuestro caso fue un PLS refractario atípico que se asemejaba a la enfermedad por crioaglutininas. Además, se observó hemoglobinuria franca relacionada con hemólisis intravascular grave. Estas características no se han descrito antes en PLS, según nuestro leal saber y entender. Además, el tratamiento IA nunca se había informado en la literatura para PLS, hasta donde sabemos. El tratamiento y el manejo podrían ser un desafío en PLS refractarios. El rituximab, la IgIV y los tratamientos extracorpóreos podrían ser beneficiosos. Debe tenerse en cuenta que los PLS refractarios pueden provocar la pérdida del injerto y del paciente (AU)

Púrpura trombótica trombocitopénica en pediatría. Reporte de un caso / Thrombotic thrombocytopenic purpura in pediatrics. A case report

La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.

Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.

Anemia hemolítica autoinmune después de la infección por Covid 19 / Autoimmune Haemolytic Anaemia After Covid 19 Infection

Since its emergence in Wuhan province in late 2019, SARS-CoV-2 infection has affected more than 520 million people and caused the death of more than 6.2 million individuals. Despite rare, several haematological disorders have been observed and associated with SARS-CoV-2 infection, in particular, autoimmune haemolytic anaemia (AIHA). We present the case of a 71-year-old man with recent SARS-CoV-2 infection, presenting with 5 weeks evolution of asthenia and loss of 10% of body weight. From the initial study, normochromic normocytic anaemia stands out with haptoglobin consumption. Direct Coombs test was positive, with positive direct antiglobulin test for IgG4. The patient was admitted and started corticosteroids therapy with prednisolone 1 mg / kg. Given that the extended etiologic study was negative, covid 19 was assumed to be the trigger of the current clinical picture. During hospitalization, the patient presented a favourable evolution with recovery of haemoglobin value and absence of haemolysis. (AU)

Desde su aparición en la provincia de Wuhan a finales de 2019, la infección por SARS-CoV-2 ha afectado a más de 520 millones de personas y ha causado la muerte de más de 6,2 millones de individuos. A pesar de ser poco frecuentes, se han observado varios trastornos hematológicos asociados a la infección por SARS-CoV-2, en particular la anemia hemolítica autoinmune (AIHA). Presentamos el caso de un varón de 71 años con infección reciente por SARS-CoV-2, que presenta astenia de 5 semanas de evolución y pérdida del 10% del peso corporal. Del estudio inicial destaca anemia normocítica normocrómica con consumo de haptoglobina. El test de Coombs directo fue positivo, con antiglobulina directa positiva para IgG4.El paciente fue ingresado y se inició tratamiento con corticosteroides con prednisolona 1 mg / kg. Dado que el estudio etiológico ampliado fue negativo, se asumió que el covid 19 era el desencadenante del cuadro clínico actual. Durante la hospitalización, el paciente presentó una evolución favorable con recuperación del valor de hemoglobina y ausencia de hemólisis. (AU)

Manejo anestésico del déficit de glucosa 6-fosfato deshidrogenasa / Anesthetic management of glucose 6-phosphate dehydrogenase deficiency

El déficit de glucosa 6-fosfato deshidrogenasa es la enzimopatía más frecuente de los glóbulos rojos, contando con una prevalencia de 400 millones de personas en el mundo y una herencia ligada al cromosoma X, afectando sobre todo a varones. La glucosa 6-fosfato-deshidrogenasa participa en la vía de las pentosas-fosfato, encargada del metabolismo celular, y produciendo antioxidantes. Un déficit de esta enzima altera su capacidad de proteger a los hematíes del estrés oxidativo que producen ciertos medicamentos, condiciones metabólicas, infecciones y alimentos. Se requieren consideraciones anestésicas específicas para disminuir la morbimortalidad asociada a intervenciones médico-quirúrgicas en pacientes con esta enfermedad. En este artículo se expone el caso de un varón de 45 años con este déficit enzimático sometido a anestesia general combinada para resección anterior baja de recto programada.(AU)

Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme disease of red blood cells, with around 400 million people suffering from it throughout the world and linked to the X chromosome inheritance, thus it predominantly affects men. Glucose 6-phosphate-dehydrogenase participates in the pentose-phosphate pathway, being responsible for cellular metabolism and the production of antioxidants. A deficiency of this enzyme alters its ability to protect red blood cells from oxidative stress caused by certain drugs, metabolic conditions, infections and food. Specific anesthetic considerations are required to reduce the morbidity and mortality associated with medical-surgical interventions in patients with this disease. This article presents the case of a 45-year-old man with Glucose 6-Phosphate Dehydrogenase deficiency who underwent combined general anesthesia for programmed low anterior resection of the rectum.(AU)

Microangiopatías trombóticas en niños críticamente enfermos. Registro español MATUCIP / Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain

Introducción: Las microangiopatías trombóticas (MAT) son entidades infrecuentes que suelen causar afectación renal, hematológica, neurológica y cardiovascular, con síntomas inespecíficos pero graves. Con la finalidad de mejorar el conocimiento de sus características clínicas, el proceso diagnóstico y el tratamiento en la fase aguda, se ha creado el registro de MAT en las unidades de cuidados intensivos pediátricos (UCIP) de España (Registro MATUCIP). Pacientes y métodos: Estudio observacional, multicéntrico, realizado en 20 UCIP españolas desde enero de 2017 hasta diciembre de 2021 que incluyó niños mayores de 1mes con diagnóstico de MAT y seguimiento hasta el alta de la UCIP. Resultados: Se incluyeron 97 pacientes (51,5% mujeres), con una mediana de edad de 2,6años (RIQ: 1,6-5,7). La clínica inicial fue de tipo gastrointestinal (74,2%), respiratoria (14,4%), cuadro febril (5,2%), neurológica (3,1%) y otras (3,1%). Al ingreso, el 75,3% presentaban anemia hemolítica microangiopática, el 95,9% trombocitopenia y el 94,8% daño renal agudo. Fueron diagnosticados de síndrome hemolítico urémico (SHU) asociado a Escherichia coli productora de toxina Shiga el 57,7%, SHU por Streptococcus pneumoniae el 14,4%, SHU atípico el 15,6%, MAT secundaria el 10,3% y púrpura trombótica trombocitopénica el 2,1%. Desarrollaron hipertensión arterial el 89,7%, manifestaciones digestivas el 49,5%, respiratorias el 22,7%, neurológicas el 25,8% y cardiacas el 12,4%. El 60,8% requirieron depuración extrarrenal y el 2,1%, plasmaféresis. Recibieron eculizumab 20 pacientes. La mediana de estancia en la UCIP fue de 8,5días (RIQ: 5-16,5). Dos niños fallecieron. (AU)

Introduction: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. Patients and methods: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1month with TMAs, who were followed up through the discharge from the PICU. Results: The sample included 97 patients (51.5% female) with a median age of 2.6years (interquartile range [IQR]: 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5days (IQR: 5-16.5). Two children died. (AU)

Thrombotic microangiopathies in critically ill children: The MATUCIP registry in Spain.

INTRODUCTION: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. METHODS: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. RESULTS: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6-5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5-16.5). Two children died. CONCLUSIONS: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data.

Anesthetic management of glucose 6-phosphate dehydrogenase deficiency.

Glucose 6-phosphate dehydrogenase deficiency is the most common enzyme disease of red blood cells, with around 400 million people suffering from it throughout the world and linked to the X chromosome inheritance, thus it predominantly affects men. Glucose 6-phosphate-dehydrogenase participates in the pentose-phosphate pathway, being responsible for cellular metabolism and the production of antioxidants. A deficiency of this enzyme alters its ability to protect red blood cells from oxidative stress caused by certain drugs, metabolic conditions, infections and food. Specific anesthetic considerations are required to reduce the morbidity and mortality associated with medical-surgical interventions in patients with this disease. This article presents the case of a 45-year-old man with glucose 6-phosphate dehydrogenase deficiency who underwent combined general anaesthesia for programmed low anterior resection of the rectum.

Radiocirugía estereotáxica por gamma knife en un paciente con cavernoma cerebral y síndrome de Evans

El cavernoma cerebral es una malformación vascular de diagnóstico infrecuente. Se define como una malformación a nivel de la vasculatura microcerebral que, dependiendo a la ubicación y si existe la posibilidad de ruptura, conlleva a una emergencia que puede terminar en la muerte del paciente. En esta oportunidad se reporta el caso de un paciente con cavernoma cerebral asociado al síndrome de Evans. Se decide manejo quirúrgico de la lesión por aumento de intensidad de cefalea e intolerancia oral. Dada la coexistencia del Síndrome de Evans y la alta tasa de morbimortalidad es que se decide manejo quirúrgico mediante radiocirugía estereotáxica con gamma knife. El uso de dosis de margen bajo para tratamiento con gamma knife para uso en cavernomas cerebrales produce un manejo controlado para sintomatología de convulsiones y mejor expectativa de calidad de vida.

Cerebral cavernoma is an infrequently diagnosed vascular malformation. It is defined as a malformation at the level of the microcerebral vasculature that, depending on the location and if there is a possibility of rupture, leads to an emergency that can end in the death of the patient. On this occasion, we report a case of a patient with cerebral cavernoma associated with Evans syndrome. Surgical management of the lesion was decided due to increased intensity of headache and oral intolerance. Given the coexistence of Evans Syndrome and the high rate of morbidity and mortality, surgical management was decided by stereotaxic radiosurgery with a gamma knife. The use of low-margin doses for treatment with gamma knife for use in brain cavernomas produces controlled management for seizure symptoms and better quality of life expectancy.

Anemia hemolítica autoinmune / Autoimmune haemolytic anaemia

Las anemias hemolíticas autoinmunes (AHAI) son trastornos hematológicos adquiridos ocasionados por una destrucción periférica de eritrocitos incrementada, mediada por autoanticuerpos dirigidos frente a antígenos eritrocitarios. Se clasifican según etiología en primarias y secundarias, y según el tipo de anticuerpo detectado y temperatura de reacción en AHAI por anticuerpos calientes (AHAI-C) y AHAI por anticuerpos fríos (AHAI-F).El pilar del manejo en AHAI-C continúa siendo el tratamiento con glucocorticoides, y la adición precoz de rituximab ha demostrado buenos resultados en los últimos estudios. Las AHAI-F primarias se tratan principalmente con rituximab, solo o combinado con quimioterapia.En fase de desarrollo avanzado encontramos nuevos fármacos como los inhibidores de Syk, Ig anti-FcRn e inhibidores del complemento, que permitirán ampliar el arsenal terapéutico, especialmente en casos refractarios o recidivantes. (AU)

Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA).The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy.New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases. (AU)

[Autoimmune haemolytic anaemia]. / Anemia hemolítica autoinmune.

Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA). The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy. New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases.

Human adenovirus associated with severe cold agglutinin syndrome: a rare complication in Pediatrics / Adenovírus humano associado à síndrome da aglutinina fria grave: uma complicação rara em Pediatria

ABSTRACT Objective: The objectives of this study were to describe the first pediatric case of cold agglutinin syndrome (CAS) triggered by human adenovirus and review the literature. Case description: This case report involves a previously healthy, 2½-year-old female child with human adenovirus isolated in a nasal swab. At 72 h after admission, the patient progressed to a severe episode of anemia (hemoglobin level: 2.6 g/dL). The laboratory findings were consistent with CAS. The patient received blood transfusion, vitamin supplementation, adequate hydration, and thermal protection. At her last follow-up, 1 year after her initial presentation, she remains clinically well without signs of hemolysis. Comments: While severe CAS is extremely uncommon in the pediatric emergency department, human adenovirus infection is a common illness in pediatrics. Recently, the adenovirus has been associated with new complications (acute hepatitis and fulminant liver failure). Pediatric physicians and hematologists should be aware of unusual evolution, signs, and symptoms of this infection that warrant more urgent medical attention. In this case, the hematologic complication suspicion was the key to early diagnosis and adequate management.

RESUMO Objetivo: Descrever o primeiro caso pediátrico de síndrome da crioaglutinina desencadeado por adenovírus humano e revisar a literatura. Descrição do caso: Paciente do sexo feminino, dois anos e seis meses, previamente hígida e diagnosticada com adenovírus humano isolado em swab nasal. Após 72 horas da admissão, a paciente evoluiu com quadro de anemia grave (hemoglobina de 2,6 g/dL). Os achados laboratoriais foram compatíveis com síndrome da crioaglutinina. A paciente recebeu transfusão de concentrado de hemácias, suplementação vitamínica, hidratação adequada e proteção térmica. Em seu último retorno ambulatorial, um ano após a apresentação inicial, permanecia clinicamente bem, sem sinais de hemólise. Comentários: Enquanto a síndrome da crioaglutinina grave é extremamente incomum na emergência pediátrica, a infecção por adenovírus humano é um quadro comum na infância. Recentemente, o adenovírus tem sido associado a novas complicações, e pediatras e hematologistas devem ficar atentos à possibilidade de uma evolução incomum dessa infecção e dos sinais e sintomas que possam necessitar de atenção urgente. No caso apresentado, a suspeita da complicação hematológica foi a chave para o diagnóstico precoce e seu manejo adequado.

Conversion of the etiology of autoimmune hemolytic anemia / Conversión de etiología de anemia hemolítica autoinmune

Autoimmune hemolytic anemia (AIHA) is disorder that involves the destruction of erythrocytes, differentiating between warm AIHA (WAIHA) with extravascular hemolysis mediated by IgG, cold agglutinin disease (CAD) with intravascular hemolysis mediated by IgM/Cd3 or mixed AIHA. Treatment of WAIHA consists of corticosteroids, immunoglobulins, rituximab, immunosuppressants, cyclophosphamide and splenectomy, whereas in CAD the response to corticosteroids is low.The 46-year-old patient came to the emergency department with a drop of 4.5 hemoglobin points in 15 days, associated with tachycardia, muco-cutaneous pallor and dyspnea. After analytical parameters compatible with AIHA and Coombs test Cd3+/IgM-, a diagnosis of CAD was made and rituximab and warm transfusion support were started. When intravascular haemolysis intensified, intravenous immunoglobulin, plasmapheresis and darbepoetin alpha were associated with no clinical improvement, later receiving bortezomib as third line and eculizumab due to refractoriness. The Coombs’ test was repeated, with a result compatible with WAIHA and slight splenomegaly associated due to extravascular hemolysis, so a splenectomy was performed achieving stabilization of analytical parameters and allowing the patient to be discharged. This clinical case evidences a conversion in the etiology of AIHA, with initial diagnosis of CAD since Coombs’ test was Cd3+/IgG- and converted to WAIHA after 37 days of admission since Coombs’ test changed to Cd3-/IgG+. (AU)

La anemia hemolítica autoinmune (AIHA) es una patología que conlleva la destrucción de eritrocitos, diferenciando entre AIHA por anticuerpos calientes (WAIHA) con hemólisis extravascular por IgG, AIHA por crioaglutininas (CAD) con hemólisis intravascular por IgM/Cd3 o AIHA mixtas. El tratamiento de AIHA por anticuerpos calientes consiste en corticoides, inmunoglobulinas, rituximab, inmunosupresores, ciclofosfamida y esplenectomía, mientras que en AIHA por crioaglutininas la respuesta a corticoides es baja. La paciente de 46 años acudió a urgencias con caída de 4,5 puntos de hemoglobina en 15 días, asociando taquicardia, palidez y disnea. Tras parámetros analíticos compatibles con AIHA y test de Coombs Cd3+/IgM- se diagnosticó de CAD e inició rituximab y transfusiones con calentador. Ante una intensificación de la hemólisis intravascular se asoció inmunoglobulina intravenosa, plasmaféresis y darbepoetina alfa sin mejoría clínica, recibiendo posteriormente bortezomib como tercera línea y eculizumab ante refractariedad. Se repitió el test de Coombs evidenciando en ese momento un diagnóstico por WAIHA, con ligera esplenomegalia asociada a la hemólisis extravascular, por lo que se realizó una esplenectomía alcanzando una estabilización de los parámetros analíticos y permitiendo el alta de la paciente. Este caso clínico evidencia una conversión en la etiología de la AIHA, con diagnóstico inicial de CAD ante test de Coombs Cd3+/IgG- y cambio a WAIHA después de 37 días de ingreso ante Coombs Cd3-/IgG+. (AU)

Déficit de glucosa-6-fosfato deshidrogenasa asociado a rasgo falciforme: importancia de una buena historia clínica / Glucose-6-phosphate dehydrogenase deficiency associated with sickle cell trait: importance of a good medical history

Introducción: El déficit de glucosa-6-fosfato deshidrogenasa es la alteración enzimática más frecuente a nivel eritrocitario. El debut característico lo constituye un paciente previamente sano en el que se desencadena una crisis hemolítica por determinados fármacos, infecciones o alimentos. En este último contexto es conocido como favismo el cuadro clínico secundario a la ingesta de habas. Caso clínico. Varón de 23 meses que consulta por fiebre, ictericia, palidez y coluria. Como antecedente personal de interés destaca la determinación de un rasgo falciforme en el cribado neonatal. Los resultados de la analítica sanguínea son compatibles con una crisis hemolítica no inmune, por lo que se establece como hipótesis diagnóstica una anemia hemolítica desencadenada por proceso infeccioso en paciente con rasgo falciforme. Puesto que el rasgo falciforme es asintomático, durante el ingreso se amplíó la anamnesis detectándose al menos un episodio de similares características, pero más leve, y al incidir en la dieta familiar se confirmó la ingesta intermitente de habas. Ante la posibilidad de favismo se solicitó análisis genético que confirmó el diagnóstico. Conclusiones. Las complicaciones de las enfermedades de base de cada paciente frecuentemente causan sus patologías, pero no siempre es así. Es fundamental realizar una anamnesis exhaustiva, dado que esta puede ofrecer claves diagnósticas inesperadas.(AU)

Introduction. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymatic alteration at the erythrocyte level. The characteristic onset is a previously healthy patient in whom a hemolytic crisis is triggered by certain drugs, infections or foods. In this latter context, the clinical condition secondary to the ingestion of broad beans is known as favism. Clinical case. A 23-month-old male presented with fever, jaundice and choluria. As a personal history of interest, the determination of a sickle cell trait in neonatal screening stands out. The blood test results are compatible with a non-immune hemolytic crisis, so the diagnostic hypothesis is established as a hemolytic anemia triggered by an infectious process in a patient with sickle cell trait. During their stay in the ward, the anamnesis is expanded, detecting at least one episode with similar but milder characteristics and by influencing the family diet, the intermittent intake of beans at least once a month is confirmed. Given the possibility of favism, genetic analysis is requested to confirm the diagnosis. Conclusions. The complications of each patient’s underlying diseases often cause their pathologies, but this is not always the case. It is essential to carry out an exhaustive anamnesis, since this can offer unexpected.(AU)

An atypical case of refractory passenger lymphocyte syndrome after renal transplantation.

BACKGROUND: Passenger lymphocyte syndrome (PLS) causes immune-mediated hemolysis in solid and bone marrow transplant recipients. Donor-derived antibodies against the recipient erythrocyte drive the pathogenesis. It is a rare entity in kidney transplantation, and most of the cases are self-limited. CASE PRESENTATION: A 36-year-old woman presented with fatigue 13 days after living donor renal transplantation. The operation was uneventful, and she was discharged with normal graft functions on the 11th day of transplantation Findings were consistent with cold agglutinin disease at her admission. However, the cold agglutinin test was negative. Eventually, she was diagnosed with PLS. Refractory intravascular hemolysis and frank hemoglobinuria were also present in the patient. Hemolysis was resistant to steroids, intravenous immunoglobulin (IVIG), and Rituximab. Because of life-threatening anemia related to refractory PLS, mycophenolate and tacrolimus were interrupted. However, hemolysis persisted. Following that, immunoadsorption (IA) treatment was obtained. Unfortunately, graft loss occurred due to rejection despite the resolution of PLS after IA. CONCLUSION: PLS is a rare and usually self-limited entity. Our case was an atypical refractory PLS that resembled cold agglutinin disease. Also, frank hemoglobinuria was observed related to severe intravascular hemolysis. These features have not been described before in PLS, to the best of our knowledge. Additionally, IA treatment had never been reported in the literature for PLS, as far as we know. Treatment and management could be a challenge in refractory PLS. Rituximab, IVIG, and extracorporeal treatments could be beneficial. It should be borne in mind that refractory PLS can cause graft and patient loss.

Síndrome del linfocito pasajero por anticuerpos anti-D en trasplante hepático. Reporte de caso / Passenger lymphocyte syndrome due to anti-D antibodies in liver transplantation. Case report

Resumen El síndrome del linfocito pasajero (PLS) es una complicación de injerto contra huésped que se presenta en el trasplante de órganos sólidos o en el trasplante de células progenitoras hematopoyéticas. Es una causa importante de hemólisis inmune después del trasplante causada por la producción de anticuerpos por parte de los clones específicos de linfocitos B viables transferidos a través del órgano del donante contra los antígenos de los glóbulos rojos del receptor. Generalmente ocurre en los trasplantes con discordancia menor ABO o Rh. Este estudio descriptivo describe el caso de un paciente de 54 años con grupo sanguíneo O/Rh(D) positivo, con cirrosis secundaria a enfermedad metabólica asociada al hígado graso (MAFLD) que fue llevado a trasplante hepático de donante O/Rh(D) negativo. A los 9 días del trasplante presentó una anemia hemolítica inmune por anticuerpos anti-D por efecto del linfocito B pasajero del donante sensibilizado. El paciente recibió medidas de soporte, transfusión de glóbulos rojos e inmunosupresión con esteroides, con lo que se logró la estabilización de los parámetros hemolíticos. En conclusión, esta es una entidad que se debe sospechar en caso de anemia hemolítica aguda en el período postrasplante.

Abstract Passenger lymphocyte syndrome (PLS) is a graft-versus-host complication in solid organ transplantation or hematopoietic stem cell transplantation. It is a major cause of immune hemolysis after transplantation caused by the production of antibodies by the specific clones of viable B lymphocytes transferred through the donor organ against the antigens of the recipient's red blood cells. It usually occurs in transplants with minor ABO or Rh mismatch. This descriptive study explains the case of a 54-year-old patient with O/Rh(D) positive blood group, with cirrhosis secondary to metabolic disease associated with fatty liver (NAFLD), who underwent liver transplantation from an O/Rh(D) negative donor. Nine days after the transplant, the patient presented with immune hemolytic anemia due to anti-D antibodies because of the transient B lymphocyte from the sensitized donor. The patient received support measures, transfusion of red blood cells, and immunosuppression with steroids, which stabilized the hemolytic parameters. In conclusion, this entity should be suspected in the case of acute hemolytic anemia in the post-transplant period.

Infección por virus de epstein barr y debut de lupus eritematoso sistémico (LES) en un adolescente / Epstein barr virus infection and systemic lupus erythematosus (SLE) debut in an adolescent / Infecção pelo vírus Epstein Barr e início de lúpus eritematoso sistêmico (LES) em adolescente

Introducción: El lupus eritematoso sistémico (LES), prototipo de enfermedad autoinmune, cursa con empujes y remisiones. Dada la diversidad de presentaciones posibles, su diagnóstico y tratamiento son un reto para el clínico, y se requiere tener un alto índice de sospecha. Objetivo: presentar el caso clínico de un adolescente que debuta con LES a forma de anemia hemolítica, probablemente gatillado por infección por virus de Epstein Barr. Caso clínico: Varón de 14 años, sin antecedentes a destacar. Consulta por fiebre de 7 días de evolución de hasta 39º C, odinofagia, astenia y adinamia. Al examen físico se constata palidez cutáneo mucosa, ictericia, adenopatías cervicales y hepatoesplenomegalia. El laboratorio muestra anemia severa regenerativa con aumento de las bilirrubinas a expensas de la indirecta sin hepatitis. Prueba de Coombs positiva. Anticuerpos específicos para Epstein Barr positivos, con lo que se diagnostica anemia hemolítica secundaria a mononucleosis y se inicia tratamiento corticoideo. En la evolución agrega eritema malar y limitación en flexión de codos y rodillas. Se reciben anticuerpos antinucleares y anti ADN nativo positivos con hipocomplementemia severa. Con diagnóstico de LES se inicia hidroxicloroquina y azatioprina, manteniéndose la prednisona. Conclusiones: Muchos virus (hepatitis C, Parvovirus B19, Epstein Barr y Citomegalovirus) se han descrito como posibles inductores o simuladores de LES. Es necesario mantener un alto índice de sospecha para realizar un diagnóstico oportuno y tratamiento precoz.

Introduction: Systemic lupus erythematosus (SLE), prototype of autoimmune disease, progresses with flares and remissions. Given the diversity of possible presentations, its diagnosis and treatment are a challenge for the clinician, and a high index of suspicion is required. Objective: To present the clinical case of an adolescent who debuted with SLE in the form of hemolytic anemia, probably triggered by Epstein Barr virus infection. Clinical case: 14 - year - old male, with no history to highlight. Consultation for fever of 7 days of evolution of up to 39º C, odynophagia, asthenia and adynamia. Physical examination revealed mucous skin pallor, jaundice, cervical lymphadenopathy, and hepatosplenomegaly. The laboratory shows severe regenerative anemia with increased bilirubin at the expense of indirect without hepatitis. Positive Coombs test. Specific antibodies for Epstein Barr were positive, with which hemolytic anemia secondary to mononucleosis was diagnosed and corticosteroid treatment was started. In the evolution, it adds malar erythema and limitation in flexion of the elbows and knees. Positive antinuclear and anti-native DNA antibodies are received with severe hypocomplementemia. With a diagnosis of SLE, hydroxychloroquine and azathioprine were started, maintaining prednisone. Conclusions: Many viruses (hepatitis C, Parvovirus B19, Epstein Barr and Cytomegalovirus) have been described as possible inducers or mimics of SLE. It is necessary to maintain a high index of suspicion for timely diagnosis and early treatment.

Introdução: O lúpus eritematoso sistêmico (LES), protótipo de doença autoimune, evolui com impulsos e remissões. Dada a diversidade de apresentações possíveis, seu diagnóstico e tratamento são um desafio para o clínico, sendo necessário um alto índice de suspeição. Objetivo: apresentar o caso clínico de uma adolescente que iniciou com LES na forma de anemia hemolítica, provavelmente desencadeada por infecção pelo vírus Epstein Barr. Caso clínico: Homem de 14 anos, sem antecedentes a destacar. Consulta por febre de 7 dias de evolução de até 39º C, odinofagia, astenia e adinamia. O exame físico revelou palidez cutânea mucosa, icterícia, linfadenopatia cervical e hepatoesplenomegalia. O laboratório mostra anemia regenerativa grave com aumento da bilirrubina em detrimento da indireta sem hepatite. Teste de Coombs positivo. Anticorpos específicos para Epstein Barr foram positivos, com o qual foi diagnosticada anemia hemolítica secundária à mononucleose e iniciado tratamento com corticosteróides. Na evolução, acrescenta eritema malar e limitação na flexão dos cotovelos e joelhos. Anticorpos antinucleares e anti-DNA nativos positivos são recebidos com hipocomplementemia grave. Com diagnóstico de LES, iniciou-se hidroxicloroquina e azatioprina, mantendo-se prednisona. Conclusões: Muitos vírus (hepatite C, Parvovírus B19, Epstein Barr e Citomegalovírus) têm sido descritos como possíveis indutores ou mimetizadores do LES. É necessário manter um alto índice de suspeição para diagnóstico oportuno e tratamento precoce.

Anemia hemolítica autoinmune: mecanismos de inducción de autoinmunidad e inmunobiología / Autoimmune hemolytic anemia: mechanisms of autoimmunity induction and immunobiology

Introducción: La patogénesis de la anemia hemolítica autoinmune es un proceso complejo en el que muchos elementos tienen una función esencial que repercuten en la gran heterogeneidad clínica de la enfermedad, pero los mecanismos involucrados en su inducción se desconocen en gran medida. Objetivo: Explicar los principales mecanismos propuestos en el inicio y aparición de la anemia hemolítica autoinmune y su contribución a la fisiopatología de la enfermedad. Métodos: Se realizó una revisión de la literatura en los idiomas inglés y español, de artículos publicados en los últimos 10 años sobre mecanismos propuestos en el inicio de la anemia hemolítica autoinmune. Análisis y síntesis de la información: Los mecanismos propuestos en la inducción de la autoinmunidad contra los eritrocitos incluyen el mimetismo molecular entre antígenos endógenos y antígenos exógenos, el procesamiento desregulado de autoantígenos influenciado por factores adquiridos y la disfunción de los linfocitos B y T. Conclusiones: Los mecanismos propuestos en la aparición de la anemia hemolítica autoinmune brindan información valiosa para mejorar la comprensión de los mecanismos moleculares involucrados y subrayan la complejidad de los fenómenos involucrados en la perdida de la tolerancia hacia los eritrocitos autólogos y el delicado equilibrio entre factores genéticos y ambientales(AU)

Introduction: The pathogenesis of autoimmune hemolytic anemia is a complex process in which many elements play an essential role and have an impact on the great clinical heterogeneity of the disease, but the mechanisms involved in its induction are largely unknown. Objective: To explain the main mechanisms proposed in the initiation and occurrence of autoimmune hemolytic anemia and its contribution to the pathophysiology of the disease. Methods: A review of the literature, in English and Spanish languages, of articles published in the last 10 years on proposed mechanisms in the initiation of autoimmune hemolytic anemia was carried out. Analysis and synthesis of information: Proposed mechanisms for the induction of autoimmunity against erythrocytes include molecular mimicry between endogenous and exogenous antigens, deregulated processing of autoantigens influenced by acquired factors, and B and T cells dysfunction. Conclusions: The proposed mechanisms in the occurrence of autoimmune hemolytic anemia provide valuable information to improve the understanding of the mechanisms involved and underline the complexity of the phenomena involved in the loss of tolerance towards autologous erythrocytes and the delicate balance between genetic and environmental factors(AU)

Caracterización fisiopatológica de las anemias hemolíticas autoinmunes / Pathophysiological characterization of autoimmune hemolytic anemia

Introducción: La anemia hemolítica autoinmune se define como el aumento de la destrucción de los eritrocitos en presencia de autoanticuerpos dirigidos contra antígenos de grupos sanguíneos eritrocitarios. Objetivo: Caracterizar las anemias hemolíticas autoinmunes teniendo en cuenta las características fisiopatológicas, manifestaciones clínicas y el diagnóstico de laboratorio. Métodos: Se realizó una revisión de la literatura en inglés y español de artículos publicados en los últimos 10 años sobre anemia hemolítica autoinmune. Conclusiones: La anemia hemolítica autoinmune es una enfermedad muy heterogénea. El diagnóstico suele ser fácil, pero los casos difíciles pueden ser un desafío. La definición de cada tipo es fundamental ya que la terapia es diferente y se enfoca más con la comprensión de los mecanismos patogénicos(AU)

Introduction: Autoimmune hemolytic anemia is defined as increased destruction of red blood cells in the presence of autoantibodies directed against red cell blood group antigens. Objective: To characterize autoimmune hemolytic anemias, taking into account immunohematological, clinical, diagnostic and pathogenic mechanisms. Methods: A review of the literature, in English and Spanish, of articles published in the last 10 years on autoimmune hemolytic anemia was carried out. Conclusions: Autoimmune hemolytic anemia is a very heterogeneous disease. Diagnosis is usually easy, but difficult cases can be challenging. The definition of each type is fundamental since the therapy is different and focuses more on understanding the pathogenic mechanisms(AU)