Síndrome hemolítico urémico atípico: papel del perfil genético / Atypical hemolytic uremic syndrome: role of the genetic profile

Resumen: El síndrome hemolítico urémico es una microangiopatía trombótica caracterizada por anemia hemolítica microangiopática, trombocitopenia y daño renal agudo. El síndrome hemolítico urémico típico (el más común) es ocasionado por bacterias productoras de la toxina Shiga, típicamente por cepas de Escherichia coli. El término síndrome hemolítico urémico atípico se usa para referirse a los pacientes que padecen este cuadro por causas diferentes. Las manifestaciones clínicas y paraclínicas no son suficientes para diferenciar el síndrome hemolítico urémico atípico de otras microangiopatías trombóticas, por lo que la determinación de la actividad de ADAMTS13 y la prueba de la toxina Shiga resultan esenciales para establecer el diagnóstico preciso. Aunque en la actualidad el diagnóstico definitivo requiere confirmación genética, las pruebas genéticas son costosas y poco útiles para el diagnóstico inicial; sin embargo, más que importancia diagnóstica, tiene gran valor pronóstico, permite prescribir el tratamiento adecuado disminuyendo significativamente la morbilidad y mortalidad atribuibles a esta enfermedad.

Abstract: The haemolytic uraemic syndrome is a thrombotic microangiopathy (TMA) characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury. The typical haemolytic uraemic syndrome (tHUS, the most common) is caused by bacteria that produce Shiga toxin, typically strains of Escherichia coli. On the other hand, the term atypical haemolytic uraemic syndrome (aHUS) is used to refer to those patients who develop this condition due to different etiologies. The clinical and paraclinical manifestations are not enough to differentiate the aHUS from other thrombotic microangiopathies, so the determination of the activity of ADAMTS13 and the Shiga toxin test are essential to establish the precise diagnosis. Although currently the diagnosis requires genetic confirmation, the genetic tests are expensive and not very useful for the initial diagnosis; however, more than diagnostic importance, it has a great prognostic value allowing establishing an adequate management and significantly reducing the morbidity and mortality attributable to this condition.

Hemoglobinuria paroxística nocturna / Paroxysmal nocturnal hemoglobinuria

ResumenLa hemoglobinuria paroxística nocturna es una anemia hemolítica crónica, adquirida, poco común, que afecta con igual frecuencia ambos sexos. Se manifiesta a cualquier edad y con mayor incidencia en países del sudeste asiático. Es el resultado de la expansión clonal no maligna de células progenitoras hematopoyéticas. Se caracteriza por anemia hemolítica intravascular, tendencia a la trombosis y un componente variable de insuficiencia medular.Se asocia a otras patologías hematológicas como anemia aplásica y síndrome mielodisplásico. La citometría de flujo es el método de elección para diagnóstico. El eculizumab y el trasplante de médula ósea alogénico son las únicas terapias efectivas.

Abstract:Paroxysmal nocturnal hemoglobinuria is a rare acquired chronic hemolytic anemia, which affects both sexes with equal frequency. It occurs at any age and more frequently in Southeast Asian countries. It is the result of non malignant clonal expansion of hematopoietic progenitor cells. It is characterized by intravascular hemolytic anemia, recurrent thrombosis and a variable component of bone marrow failure. It is associated with other hematologic disorders such as aplastic anemia and myelodysplastic syndrome. Flow cytometry is the method of choice for diagnosis. Eculizumab and allogeneic bone marrow transplantation is the only effective therapies.

Clinical analysis of the microangiopathic hemolytic anemia and renal impairment secondary to methylmalonic ;academia in children / 临床儿科杂志

Objectives To review the clinical features in children with methylmalonic academia (MMA) having the primary clinical manifestations of microangiopathic hemolytic anemia and renal impairment. Methods The clinical data of 4 children diagnosed of MMA with the primary clinical manifestations of microangiopathic hemolytic anemia and renal impairment were retrospectively analyzed from August 2013 to present. Results In the four children (two boys and two girls) with the age from nine months to three years seven mouths, two children were diagnosed with MMA combined with homocysteine, and 2 children were diagnosed with MMA, but there was no homocysteine testing. All four children showed moderate to severe anemia, proteinuria, hematuria, and hypertension. One child had abnormal renal function and thrombocytopenia, and manifested as hemolytic uremic syndrome. Renal biopsy was performed in 2 children and they had glomerular sclerosis lesions with renal tubular necrosis and mesangial proliferative glomerulonephritis respectively. All children were treated with vitamin B12, and the indexes of microangiopathic hemolytic anemia and renal impairment were improved signiifcantly. Conclusions MMA may be combined with microangiopathic hemolytic anemia, renal impairment and even hemolytic uremic syndrome, and the early diagnosis and treatment is required.

Microangiopathic Hemolytic Anemia as the First Manifestation of Metastatic Signet Ring Cell Carcinoma of Unknown Origin: A Case Report and Review of Literature / 대한진단검사의학회지

Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma of an unknown origin is very rare. In this study, we present the case of an 80-yr-old man who was admitted to the hospital because of a 1-month history of lower back pain and dyspnea. He was diagnosed with MAHA on the basis of the laboratory findings that revealed anemia with schistocytes, decreased haptoglobin levels, and a negative direct Coombs' test. Bone marrow examination, which was performed because of the progression of anemia, revealed bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis. However, the primary origin of this signet ring cell carcinoma was not found. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, gastric and colorectal endoscopic examinations, bone marrow examinations, and positron emission tomography-computed tomography or bone scans.

Microangiopathic Hemolytic Anemia as the First Manifestation of Metastatic Signet Ring Cell Carcinoma of Unknown Origin: A Case Report and Review of Literature / 대한진단검사의학회지

Microangiopathic hemolytic anemia (MAHA) occurs occasionally as a paraneoplastic syndrome in some solid tumors, but MAHA accompanied by signet ring cell carcinoma of an unknown origin is very rare. In this study, we present the case of an 80-yr-old man who was admitted to the hospital because of a 1-month history of lower back pain and dyspnea. He was diagnosed with MAHA on the basis of the laboratory findings that revealed anemia with schistocytes, decreased haptoglobin levels, and a negative direct Coombs' test. Bone marrow examination, which was performed because of the progression of anemia, revealed bone marrow metastases of signet ring cell carcinoma with extensive bone marrow necrosis. However, the primary origin of this signet ring cell carcinoma was not found. When the cause of progressive MAHA is unknown, the possibility of cancer-associated MAHA must be excluded by performing additional tumor workup, including the detection of tumor markers, gastric and colorectal endoscopic examinations, bone marrow examinations, and positron emission tomography-computed tomography or bone scans.

A Case of Light Chain Deposition Disease Involving Kidney and Bone Marrow with Microangiopathic Hemolytic Anemia / 대한진단검사의학회지

We report a case of light chain deposition disease in a 59-yr-old female showing deposition of monoclonal light chain in the kidney and bone marrow accompanied with a schistocytosis, the morphologic finding of microangiopathic hemolytic anemia. The immunofluorescence examination of the kidney revealed strongly stained kappa-light chain deposits on the glomerular mesangium and capillary wall, tubules, and vessel wall. The electron microscopy demonstrated electron-dense deposits on the glomerular basement membrane and mesangium. Anemia was observed with schistocytosis and Howell-Jolly body in the peripheral blood smears. The immunohistochemical examination of the bone marrow showed the presence of kappa-light chain deposits in scattered plasma cells and thickened vessel wall in the absence of a prominent plasma cell proliferation. Although an immunofixation electrophoresis failed to detect a monoclonal gammopathy, the presence of monoclonal protein could be identified by an abnormal kappa/lambda ratio on the serum free light chain analysis.

Anemia hemolítica microangiopática induzida por tacrolimus e ciclosporina A / Microangiopathic hemolytic anemia induced by tacrolimus and ciclosporine A

Relatamos caso raro de anemia hemolítica microangiopática em paciente após transplante hepático por cirrose Child B causada por deficiência de alfa1-antitripsina. Após análise clínica e laboratorial extensa, concluiu-se que o quadro de hemólise foi causado pela medicação imunossupressora utilizada após transplante. Inicialmente foi utilizado tacrolimus que, posteriormente, foi substituído por ciclosporina A, entretanto não houve melhora da hemólise. Após suspensão das duas drogas, houve melhora importante clínica do paciente, com normalização dos parâmetros hematológicos.

We report a rare case of acute hemolysis in a patient after liver transplant for Child B cirrhosis caused by alfa1-antitripsine deficiency. History and laboratorial examinations indicated that the most probable cause of the hemolysis was the use of the immunosupressor tacrolimus and later Cyclosporine A. After the discontinuation of these drugs, there was improvement in the clinical condition of the patient, with a compensated hemolytic anemia.

Síndrome hemolítico-urêmica esporádica pós-parto / Sporadic postpartum hemolytic uremic syndrome

Anemia hemolítica microangiopática associado à trombocitopenia participa de um grupo de doenças que freqüentemente apresentam suas características clínicas muito semelhantes, sendo difícil distingui-las. A síndrome hemolítico-urêmica é dividida em duas apresentações: a forma não esporádica, que acomete comumente crianças após infecção bacteriana causando diarréia sanguinolenta, possui bom prognóstico; e a forma esporádica, que acomete adultos, sendo bem descritos casos em mulheres pósparto, é a forma sistêmica de trombocitopenia microangiopática de pior prognóstico com alta morbidade e mortalidade, cuja falência renal é o distúrbio predominante. Relatamos um caso de síndrome hemolítico-urêmica pós-parto em paciente previamente sadia, que apresentou quadro de insuficiência renal, anemia hemolítica e trombocitopenia. Instituída a terapêutica de suporte adequada e precocemente, a paciente evoluiu satisfatoriamente com normalização dos níveis pressóricos e recuperação da função renal.

Microangiopathic hemolytic associated with thrombocytopenia is part of a disease group that frequently show likeness and that's why become difficult to separate them. There are two types of hemolytic uremic syndrome (HUS); the non sporadic type and the epidemic or "typical" type that is common on childreen that is associated with diarrhea and infection caused by verotoxinaproducing E. coli with a good prognostic; and the sporadic postpartum period. It is the systemic type of mocroangiophatic thrombocytopenia of poor prognostic with high morbidity and mortality which renal failure is the main disturb. We reported a case of HUS occuring in postpartum previously healthy, that showed abrupt renal failure, hemolytic anemia and thrombocytopenia. After proper therapy the patient developed a normal blood pressure and recovery renal function.

Thrombotic Thrombocytopenic Purpura that Developed after Rectal Cancer Surgery

Thrombotic thrombocytopenic purpura (TTP) in the acute postoperative setting is a syndrome that presents with various symptoms such as microangiopathic hemolytic anemia, thrombocytopenia, fever, renal failure, and change of the patient's mental status. Though most of the previous reports of postoperative TTP have been in conjunction with cardiac or vascular surgery, it has also been reported following orthopedic and abdominal surgeries. We present here a case of a 78 year-old female who was diagnosed with rectal cancer and who developed TTP the 2nd day following her cancer surgery. Because the presentation can be confused with other early postoperative complications, TTP should be considered in the differential diagnosis of the patient who develops unexplained anemia and thrombocytopenia following an abdominal surgery. Awareness of this syndrome is essential because starting plasmapheresis early can be life-saving.

Algunas consideraciones acerca de la púrpura trombocitopénica trombótica / Some considerations about the thrombocytopenic thrombotic purpura

La púrpura trombocitopénica trombótica (PTT) es una enfermedad caracterizada por anemia hemolítica microangiopática, trombocitopenia, manifestaciones neurológicas fluctuantes y trastornos renales. La oclusión de arteriolas y capilares por microtrombos compuestos fundamentalmente por plaquetas, es típica de este trastorno, y consecuencia de la presencia de grandes multímeros de factor von Willebrand (Fv W), presumiblemente debido a la disminución de la actividad de la enzima ADAMTS13, encargada de escindir estos multímeros. El diagnóstico precoz de la PTT permite un tratamiento rápido y eficaz de este trastorno, elemento decisivo para evitar la evolución fatal de estos enfermos. La presencia de anemia y trombocitopenia no explicada por otros procesos patológicos, debe hacer sospechar el diagnóstico. El recambio plasmático es la terapéutica más efectiva y se considera el tratamiento de elección de la PTT. El uso de inmunosupresores asociados con el recambio plasmático ha sido recomendado en algunos casos. En la actualidad, el Rituximab se considera un tratamiento adicional de la PTT.

The thrombocytopenic thrombotic purpura is a disease characterized by microangiopathic hemolytic anemia, thombocytopenia , fluctuating neurological manifestations, and renal disorders. The occlusion of arterioles and capillars by microthrombi mainly composed of platelets is typical of this disorder and a consequence of the presence of large von Willebrand factor multimers, due presumptively to the reduction of the activity of the enzyme ADAMTS13 that is in charge of splitting these multimers.The early diagnosis of TTP allows a fast and efficient treatment of this disorder, a decisive element to prevent the fatal evolution of these patients. The presence of anemia and thrombocytopenia nonexplained by other pathological processes makes us suspect the diagnosis. The plasmatic turnover is the most effective therapeutics, and it should be considered the elective treatment of TTP. The use of immunosuppressors associated with the plasmatic turnover has been recommended in some cases. Nowadays, rituximab is regarded as an additional treatment of TTP.