{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T07:02:17Z","timestamp":1789714937149,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell disorder caused by somatic mutations in the\n                      <jats:italic>PIGA<\/jats:italic>\n                      gene, resulting in loss of glycosylphosphatidylinositol (GPI)\u2010anchored proteins, including the complement regulatory proteins, CD55 and CD59. Their absence leads to complement\u2010mediated intravascular hemolysis. Patients may present with anemia, hemoglobinuria, renal injury, and potentially life\u2010threatening thromboses.\n                    <\/jats:p>\n                    <jats:p>Complement inhibitors have transformed treatment for PNH. Terminal complement inhibitors reduce intravascular hemolysis and transfusion requirements but do not prevent C3\u2010mediated extravascular hemolysis. Proximal complement inhibitors address both intravascular and extravascular hemolysis, but some are associated with a higher risk of breakthrough hemolysis (BTH). This article describes a transfusion\u2010independent PNH patient on pegcetacoplan who developed severe BTH post\u2010HLA desensitization using therapeutic plasma exchange (PLE) prior to hematopoietic cell transplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The authors reflect on several potential contributors including iatrogenic removal of pegcetacoplan, TPE, IVIG, and ABO\u2010mismatched platelets, offering guidance on reducing the risk of BTH and potential management strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The authors provide a detailed description of the patient case, discussing bio\u2010, pharmacologic\u2010, and transfusion\u2010related factors which may promote BTH in PNH patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This article provides the authors' assessments highlighting the complexity of BTH in PNH patients receiving complement inhibitors, particularly in the setting of TPE and transfusion. Evaluation should consider potential precipitants of BTH, including iatrogenic drug removal and complement\u2010amplifying conditions such as transfusions. Adjunctive C5 inhibition may be required in acute settings, and further studies are needed to define optimal dosing strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70379","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:11:12Z","timestamp":1789711872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Breakthrough Hemolysis in Paroxysmal Nocturnal Hemoglobinuria: Mechanistic Insights and Management Strategies"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6869-9147","authenticated-orcid":false,"given":"Ganesh","family":"Raman","sequence":"first","affiliation":[{"name":"Hematology University of Washington  Seattle Washington USA"},{"name":"Fred Hutch Cancer Center  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5984-9775","authenticated-orcid":false,"given":"Meghana","family":"Vivek","sequence":"additional","affiliation":[{"name":"Hematology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-0623","authenticated-orcid":false,"given":"Rida","family":"Hasan","sequence":"additional","affiliation":[{"name":"Hematology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siob\u00e1n","family":"Keel","sequence":"additional","affiliation":[{"name":"Hematology University of Washington  Seattle Washington USA"},{"name":"Fred Hutch Cancer Center  Seattle Washington 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