Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.
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PMID:[Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature]. 2410 Jul 44

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, non-immune microangiopathic hemolytic anemia and acute renal failure. HUS is typically classified into two primary types: 1) HUS due to infections, often associated with diarrhea (D+HUS, Shiga toxin-producing Escherichia Coli-HUS), with the rare exception of HUS due to a severe disseminated infection caused by Streptococcus; 2) HUS related to complement, such HUS is also known as "atypical HUS" and is not diarrhea associated (D-HUS, aHUS); but recent studies have shown other forms of HUS, that can occur in the course of systemic diseases or physiopathological conditions such as pregnancy, after transplantation or after drug assumption. Moreover, new studies have shown that the complement system is an important factor also in the typical HUS, in which the infection could highlight an underlying dysregulation of complement factors. Clinical signs and symptoms may overlap among the different forms of HUS. Shiga toxin-producing Escherichia Coli (STEC) infection cause a spectrum of clinical sings ranging from asymptomatic carriage to non-bloody diarrhea, hemorrhagic colitis, HUS and death. The average interval between ingestion of STEC and illness manifestation is approximately 3 days, although this can vary between 2 and 12 days. Patients with pneumococcal HUS usually have a severe clinical picture with microangiopathic hemolytic anemia, respiratory distress, neurological involvement. The atypical HUS, in contrast to STEC-HUS which tends to occur as a single event, is a chronic condition and involves a poorer prognosis. Early diagnosis and identification of underlying pathogenic mechanism allow instating specific support measures and therapies. Typical management of STEC-HUS patients relies on supportive care of electrolyte and water imbalance, anemia, hypertension and renal failure. For the aHUS the initial management is supportive and similar to the approach for STEC-HUS; currently we have moved from the historic plasma therapy to new therapeutic approaches, first of all eculizumab, a monoclonal antibody that blocks the C5 cascade. This drug has shown an improvement in platelet count, cessation of hemolysis, improvement of renal function within a few days after the treatment. In patients with end-stage renal disease (ESRD) renal transplantation from a non-related donor and prophylactic administration of eculizumab to prevent recurrent disease in the allograft could be considered.
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PMID:Hemolytic uremic syndrome in children. 2776 15

Herein, we present an elderly onset case of aHUS successfully treated with eculizumab. An 80-year-old woman with severe anemia, thrombocytopenia, and acute renal dysfunction was admitted to our hospital. A laboratory test revealed steep elevation in the LDH level, and the peripheral blood smear showed erythrocyte fragmentations. Accordingly, we diagnosed thrombotic microangiopathy, and treatment with plasma exchange was immediately initiated. In addition, she required hemodialysis because of rapid impairment of the renal function. After excluding Shiga toxin-producing Escherichia coli infection and malignancy and confirming her ADMTS13 activity above 10%, we diagnosed aHUS, according to the Japanese diagnostic criteria for aHUS. Next, we initiated treatment with eculizumab. Her hematological findings improved 23 days after the starting of eculizumab. In addition, her renal function gradually recovered, and hemodialysis was discontinued. The genetic test for several complement regulatory genes tested negative. The onset of aHUS is reported in children or young adults and is rarely reported in elderly. However, our case suggests the importance of precisely diagnosing aHUS and initiating early administration of eculizumab for improving the outcome even in elderly patients.
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PMID:[Atypical hemolytic uremic syndrome in an elderly patient successfully treated with eculizumab]. 2951 71

In the last two years we admitted in our Hospital 38 children with acute renal failure (ARF). Six of them were affected by hemolytic uremic syndrome (HUS) atypical. The aHUS is diagnosed in the presence of thrombotic microangiopathy (MAT), renal insufficiency (GFR 5%). The clinical presentation of our children has been varied and so also its evolution. Patients observed were all male, aged 2 to 12 years, and no one had a family history of kidney disease. In four patients we documented alterations of complement factors (MCP deficiency and factor H and presence of anti factor H). Repeated blood transfusions were required in 4 patients and in 3 patients the platelet count was slightly reduced. In 5 patients we did plasmapheresis and in 3 patients dialysis (hemodialysis and peritoneal dialysis). In three patients in whom the diagnosis was not clear, renal biopsy was performed to confirm the diagnosis. Eculizumab was administered in 3 patients resistant to plasma exchange. We obtain a rapid response on MAT with normalization of platelet count. The effect on renal function was variable (complete remission in a patient, partial improvement in another, and unresponsiveness in the last). The last had on Kidney biopsy signs of severe impairment and we documented the presence of antibodies to eculizumab. HUS is a rare condition, but probably much more common than reported. In children with ARF and microangiopathic anemia is necessary evaluated complement factors as early to obtain an improved clinical response to treatment with eculizumab.
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PMID:[Atypical Hemolytic Uremic Syndrome: experience of a pediatric center]. 2971 Apr 40