{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T20:13:26Z","timestamp":1794255206593,"version":"4.9.0"},"reference-count":128,"publisher":"American Society of Hematology","issue":"25","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,6,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Complement is an elaborate system of innate immunity. Genetic variants and autoantibodies leading to excessive complement activation are implicated in a variety of human diseases. Among them, the hematologic disease paroxysmal nocturnal hemoglobinuria (PNH) remains the prototypic model of complement activation and inhibition. Eculizumab, the first-in-class complement inhibitor, was approved for PNH in 2007. Addressing some of the unmet needs, a long-acting C5 inhibitor, ravulizumab, and a C3 inhibitor, pegcetacoplan, have also now been approved for PNH. Novel agents, such as factor B and factor D inhibitors, are under study, with very promising results. In this era of several approved targeted complement therapeutics, selection of the proper drug must be based on a personalized approach. Beyond PNH, complement inhibition has also shown efficacy and safety in cold agglutinin disease, primarily with the C1s inhibitor of the classical complement pathway sutimlimab, as well as with pegcetacoplan. Furthermore, C5 inhibition with eculizumab and ravulizumab, as well as inhibition of the lectin pathway with narsoplimab, is being investigated in transplantation-associated thrombotic microangiopathy. With this revolution of next-generation complement therapeutics, additional hematologic entities, such as delayed hemolytic transfusion reaction or immune thrombocytopenia, might also benefit from complement inhibitors. Therefore, this review aims to describe state-of-the-art knowledge of targeting complement in hematologic diseases, focusing on (1) complement biology for the clinician, (2) complement activation and therapeutic inhibition in prototypic complement-mediated hematologic diseases, (3) hematologic entities under investigation for complement inhibition, and (4) other complement-related disorders of potential interest to hematologists.<\/jats:p>","DOI":"10.1182\/blood.2021012860","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T15:59:36Z","timestamp":1630943976000},"page":"3571-3582","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":80,"title":["Advancing therapeutic complement inhibition in hematologic diseases: PNH and beyond"],"prefix":"10.1182","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"first","affiliation":[{"name":"1Hematology Department, G Papanicolaou Hospital, Thessaloniki, Greece;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9gis Peffault","family":"de Latour","sequence":"additional","affiliation":[{"name":"2French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint-Louis Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France;"},{"name":"3BMT Unit, Universit\u00e9 de Paris, Paris, France;"},{"name":"4Severe Aplastic Anemia Working Party, European Group for Bone Marrow Transplantation;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-5109","authenticated-orcid":false,"given":"Antonio Maria","family":"Risitano","sequence":"additional","affiliation":[{"name":"4Severe Aplastic Anemia Working Party, European Group for Bone Marrow Transplantation;"},{"name":"5Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati, Avellino, Italy; and"},{"name":"6Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2022062315232814300_B1","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":"5","key":"2022062315232814300_B2","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1172\/JCI136094","article-title":"Complementopathies and precision medicine","volume":"130","author":"Gavriilaki","year":"2020","journal-title":"J Clin Invest."},{"issue":"9","key":"2022062315232814300_B3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41573-019-0031-6","article-title":"Clinical promise of next-generation complement therapeutics","volume":"18","author":"Mastellos","year":"2019","journal-title":"Nat Rev Drug Discov."},{"issue":"3","key":"2022062315232814300_B4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.hoc.2015.02.001","article-title":"Complement: an overview for the clinician","volume":"29","author":"Varela","year":"2015","journal-title":"Hematol Oncol Clin North Am."},{"issue":"14","key":"2022062315232814300_B5","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1056\/NEJM200104053441406","article-title":"Complement. 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