Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemolytic Uremic Syndrome (HUS) is characterized by the triad of hemolytic anemia, thrombocytopenia and acute renal failure. The most frequent form in children is caused by Shiga-toxin producing Escherichia coli. In absence of Shiga-toxin infection, the HUS is called atypical (aHUS). Some HUS are secondary to Streptococcus pneumonia or human immunodeficiency virus infection, cancer, anti-cancer drugs, or cyclosporine. During the last decade, aHUS has been demonstrated to be a disorder of complement alternative pathway regulation. aHUS must be regarded as a complex polygenic disease which results from a combination of genetic risk factors. Approximately 60% of patients have mutations in the genes encoding complement factor H (20-30% of patients), MCP (10-15%), factor I (4-10%), factor B (1-2%) or C3 (5-10%), and 6% have anti-factor H antibodies. Prognosis is severe whereas the clinical features vary according to complement abnormality. aHUS touches both children and adults, but in children very early onset is characteristic of factor H and factor I-HUS, while MCP-HUS is not observed before the age of 1. Half of patients with adult onset have a rapid evolution to end-stage renal disease, but half recover. The best prognosis is in patients with MCP (Membrane Cofactor Protein) mutation and a pediatric onset of the disease, who have a relapsing course, but a risk of end-stage renal disease of only 15-30% at 5 years follow-up. Anti-factor H antibodies-HUS is mainly observed in (pre)adolescents and appears to have a favourable outcome if treated early. There is a high risk of post-transplant recurrence in all groups, except MCP-HUS. These findings have paved the way for innovative therapeutic strategies based on complement blockade, and eculizumab, a monoclonal antibody targeting the human complement component 5, is now widely used to treat aHUS. Mutations in the gene of thrombomodulin and diacylglycerol kinase epsilon (DGKe) have been reported, suggesting the possibility of an alternative or more complex disease-causing mechanism than previously thought.
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PMID:[Pathophysiology of atypical hemolytic uremic syndrome. Ten years of progress, from laboratory to patient]. 2459 71

Histopathological findings can play an important role in the management of atypical haemolytic uraemic syndrome (aHUS). We report a case of aHUS that did not recover from anuria, despite the administration of eculizumab, with impressive histopathological findings. A 3-month-old girl was admitted because of poor feeding, vomiting, and diarrhoea without haemorrhage. She had anuria and severe hypertension, and laboratory results showed haemolytic anaemia with schizocytes, thrombocytopenia, and renal impairment. Although no mutations in the complement system or diacylglycerol kinase epsilon were detected, she was diagnosed with aHUS owing to the clinical course and by the exclusion of Escherichia coli infection and thrombotic thrombocytopenic purpura. Plasma exchange was performed once at day 2 and eculizumab therapy was started from day 18, with a severe infusion reaction at the first administration. After the initiation of eculizumab, although the serum lactate dehydrogenase level improved gradually, she did not recover from anuria. Pathological findings of the kidney biopsy at day 37 included diffuse arteriolar and arterial luminal stenosis with remarkable thickness and sclerotic changes of the media and intima, which are suggestive of aHUS. In addition, most glomeruli had global sclerosis and were collapsed, and 80% of the tubulointerstitial compartment showed atrophic changes with infiltration of inflammatory cells. The present case is possibly a kidney-specific fulminant type of aHUS. Although showing efficacy against thrombotic microangiopathy, eculizumab did not improve kidney function. The pathological findings reflected the severe and irreversible kidney injury.
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PMID:Irreversible severe kidney injury and anuria in a 3-month-old girl with atypical haemolytic uraemic syndrome under administration of eculizumab. 2681 19