What are the guideline sources, guidelines and references for Atypical hemolytic uremic syndrome ?
Guideline sources The following summarized guidelines for the evaluation and management of atypical hemolytic uremic syndrome (aHUS) are prepared by our editorial team based on guidelines from the Korean Working Group on Atypical Hemolytic Uremic Syndrome (KHWG 2016) and the British Society for Haematology (BSH 2010). 1 2 3 4 4 5 Definition AHUS is a complement-mediated disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. 3 Epidemiology AHUS is most commonly caused by dysregulation of the alternative complement pathway. 4 Disease course The failure of complement regulation results in aHUS, which presents with clinical manifestations of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Extra-renal manifestations include altered consciousness, seizures, focal neurologic deficits, prodromic diarrhea, hypertension, and malaise. Disease progression may lead to end-stage renal disease. 5 https://web.pathway.md/diseases/reciRWE60gPxQD7RF 1/4 6/23/23, 3:15 AM Atypical hemolytic uremic syndrome Pathway Prognosis and risk of recurrence AHUS is associated with an overall mortality rate of 25%. 4 Guidelines 1. Screening and diagnosis Clinical presentation: Suspect atypical HUS in patients with: clinical evidence of thrombotic microangiopathy no evidence of STEC-associated HUS no evidence of TTP (ADAMTS13 activity > 10%). B 2. Diagnostic investigations ADAMTS13 activity: As per KHWG 2016 guidelines, obtain tests for ADAMTS13 activity to exclude TTP in all patients suspected of having atypical HUS. B As per BSH 2010 guidelines, obtain tests for ADAMTS13 activity in all patients with a clinical diagnosis of aHUS. If ADAMTS13 activity is found to be < 10%, specific assays to detect inherited deficiency or anti-ADAMTS13 antibodies should be undertaken. B Complement testing: As per KHWG 2016 guidelines, obtain testing for complement level abnormalities (C3, C4, factor H, factor I, factor B) in all patients with atypical HUS. B As per BSH 2010 guidelines, obtain testing for complement level abnormalities (C3, C4, factor H and factor I) in all patients with atypical HUS, as the results can guide prognosis and transplantation options. B Shiga toxin test: obtain tests for Shiga toxin/enterohemorrhagic E. coli to exclude STEC-HUS for all patients suspected of having atypical HUS. B Anti-factor H antibodies: As per KHWG 2016 guidelines, test for anti-factor H antibodies in all patients with atypical HUS. B As per BSH 2010 guidelines, test for anti-factor H antibodies in all patients with atypical HUS. B Plasma homocysteine, methionine, and methylmalonic acid: obtain tests for plasma homocysteine, methionine, and MMA to exclude cobalamin defect HUS for all patients suspected of having atypical HUS. B Other laboratory tests: consider obtaining other laboratory tests for rare associated conditions in patients with thrombotic microangipathies: DIC panel, autoimmune serology, paroxysmal https://web.pathway.md/diseases/reciRWE60gPxQD7RF 2/4 6/23/23, 3:15 AM Atypical hemolytic uremic syndrome Pathway nocturnal Hgburia screening by flow cytometry, and human immunodeficiency virus screening. B FACS analysis: obtain FACS for expression of CD46 on peripheral blood mononuclear cells in all patients presenting with clinical features compatible with a diagnosis of atypical HUS. B Genetic testing: As per KHWG 2016 guidelines, perform genetic screening for complementary abnormalities in patients with atypical HUS. B As per BSH 2010 guidelines, test for mutations in factor H, factor I, factor B, CD46 and C3 in all patients with atypical HUS. If mutations are found in other genes in the research setting then these should be incorporated into the molecular diagnostic portfolio. B 3. Diagnostic procedures Tissue biopsy: consider performing tissue biopsies on a case-by-case basis in patients with suspected atypical HUS. C 4. Medical management Eculizumab: Administer eculizumab, where available, as first-line treatment for patients with symptomatic atypical HUS. B Provide meningococcal vaccination to all patients scheduled to receive eculizumab, prior to administering the first dose. A 5. Therapeutic procedures Plasma exchange: As per KHWG 2016 guidelines, offer a trial of plasma exchange and/or plasma infusion to all patients who are clinically suspected of having atypical HUS, if eculizumab is not available. B As per BSH 2010 guidelines, offer a trial of plasma exchange and/or plasma infusions to all patients with atypical HUS. B 6. Surgical interventions Kidney/liver transplantation: Avoid performing renal transplantation alone in patients with atypical HUS. D Consider performing isolated liver transplantation or a combined liver and kidney transplantation in patients with a factor H, factor I, factor B, or C3 mutation. C https://web.pathway.md/diseases/reciRWE60gPxQD7RF 3/4 6/23/23, 3:15 AM Atypical hemolytic uremic syndrome Pathway 7. Patient education Trigger avoidance: counsel patients with atypical HUS who have achieved clinical remission to avoid any identifiable trigger factors as much as possible. B References 1. C Mark Taylor, Sam Machin, Stephen J Wigmore et al. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010 Jan;148 1 37 47. Open 2. Hae Il Cheong, Sang Kyung Jo, Sung Soo Yoon et al. Clinical Practice Guidelines for the Management of Atypical Hemolytic Uremic Syndrome in Korea. J Korean Med Sci. 2016 Oct;31 10 1516 28. Open 3. David Kavanagh, Tim H Goodship, Anna Richards. Atypical hemolytic uremic syndrome. 2013 Nov;33 6 508 30.2013 Nov;33 6 508 30. Open 4. Vahid Afshar-Kharghan. Atypical hemolytic uremic syndrome. 2016 Dec 2;2016 1 217 225.2016 Dec 2;2016 1 217 225. Open 5. Kuixing Zhang, Yuxin Lu, Kevin T Harley et al. Atypical Hemolytic Uremic Syndrome: A Brief Review. 2017 Jun 1;9 2 7053.2017 Jun 1;9 2 7053. Open https://web.pathway.md/diseases/reciRWE60gPxQD7RF 4/4