{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:44:20Z","timestamp":1782963860469,"version":"3.54.5"},"reference-count":41,"publisher":"American Society of Hematology","issue":"1","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disease caused by expansion of a stem cell that harbors a somatic mutation in PIGA. PIGA mutant blood cells are deficient in the complement regulator proteins CD55 and CD59, making them susceptible to intravascular hemolysis due to a failure to regulate the APC on erythrocytes. Eculizumab is a monoclonal antibody that binds to C5 and inhibits terminal complement by interfering with the cleavage of C5 by the C5 convertases. The drug is approved by the US Food and Drug Administration for the treatment of aHUS and PNH; however, a new generation of complement inhibitors that block C5 and other components of the complement cascade is showing promise in preclinical and clinical trials.<\/jats:p>","DOI":"10.1182\/asheducation-2018.1.371","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T22:13:59Z","timestamp":1555452839000},"page":"371-376","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":23,"title":["Complement-driven anemia: more than just paroxysmal nocturnal hemoglobinuria"],"prefix":"10.1182","volume":"2018","author":[{"given":"Samuel A.","family":"Merrill","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Brodsky","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"14","key":"2019111520532579700_B1","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1016\/j.molimm.2011.04.004","article-title":"Complement factor I in health and disease","volume":"48","author":"Nilsson","year":"2011","journal-title":"Mol Immunol"},{"issue":"4","key":"2019111520532579700_B2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.blre.2017.02.003","article-title":"Complementopathies","volume":"31","author":"Baines","year":"2017","journal-title":"Blood Rev"},{"key":"2019111520532579700_B3","doi-asserted-by":"crossref","first-page":"17028","DOI":"10.1038\/nrdp.2017.28","article-title":"Paroxysmal nocturnal haemoglobinuria","volume":"3","author":"Hill","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2019111520532579700_B4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1182\/blood-2012-07-441857","article-title":"CD59 deficiency is associated with chronic hemolysis and childhood relapsing immune-mediated polyneuropathy","volume":"121","author":"Nevo","year":"2013","journal-title":"Blood"},{"issue":"6","key":"2019111520532579700_B5","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: a new complement activation pathway","volume":"12","author":"Huber-Lang","year":"2006","journal-title":"Nat Med"},{"issue":"4","key":"2019111520532579700_B6","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1111\/j.1582-4934.2008.00350.x","article-title":"The alternative complement pathway revisited","volume":"12","author":"Harboe","year":"2008","journal-title":"J Cell Mol Med"},{"issue":"1","key":"2019111520532579700_B7","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.molimm.2015.03.246","article-title":"Atypical aHUS: State of the art","volume":"67","author":"Nester","year":"2015","journal-title":"Mol Immunol"},{"issue":"23","key":"2019111520532579700_B8","doi-asserted-by":"crossref","first-page":"3637","DOI":"10.1182\/blood-2015-02-629683","article-title":"Modified Ham test for atypical hemolytic uremic syndrome","volume":"125","author":"Gavriilaki","year":"2015","journal-title":"Blood"},{"issue":"23","key":"2019111520532579700_B9","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1056\/NEJMoa1208981","article-title":"Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome","volume":"368","author":"Legendre","year":"2013","journal-title":"N Engl J Med"},{"issue":"3","key":"2019111520532579700_B10","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1182\/blood-2017-02-770214","article-title":"Eculizumab cessation in atypical hemolytic uremic syndrome","volume":"130","author":"Merrill","year":"2017","journal-title":"Blood"},{"issue":"4","key":"2019111520532579700_B11","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1053\/j.ajkd.2014.01.434","article-title":"Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases","volume":"64","author":"Ardissino","year":"2014","journal-title":"Am J Kidney Dis"},{"issue":"3","key":"2019111520532579700_B12","first-page":"310","article-title":"Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome","volume":"10","author":"Macia","year":"2017","journal-title":"Clin Kidney J"},{"issue":"5","key":"2019111520532579700_B13","first-page":"1122","article-title":"Hypertension in pregnancy. 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