Paroxysmal Nocturnal Hemoglobinuria After Vaccination: A Systematic Pharmacovigilance Analysis of 147 Cases

Paroxysmal Nocturnal Hemoglobinuria After Vaccination: A Systematic Pharmacovigilance Analysis of 147 Cases | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Paroxysmal Nocturnal Hemoglobinuria After Vaccination: A Systematic Pharmacovigilance Analysis of 147 Cases Robert W. Chandler MD, Amy W. Kelly, Albert Benavides This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9645631/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract Background Paroxysmal nocturnal hemoglobinuria (PNH) creates intrinsic susceptibility to complement-mediated hemolysis, while terminal complement inhibition increases vulnerability to invasive Neisseria infection. Vaccination may activate complement inducing hemolysis in PNH patients when given, as recommended by regulatory agencies, before complement-inhibitor therapy is initiated or optimized. Methods We performed a pharmacovigilance analysis of PNH Vaccine Adverse Event Recording System (VAERS) reports through February 2026. Eighteen PNH-related search terms were applied across seven VAERS fields. Candidate reports underwent physician review, pairwise deduplication, five-tier PNH confirmation, clinical classification, and archival recovery of modified, blanked (absence of VAERS narrative or structured-field content that was present and publicly available in earlier archived versions), or removed records. Results Among 500 candidate reports, 147 unique patient-events met inclusion criteria. Primary hemolysis was the largest category (55/147), followed by breakthrough meningococcal disease (32/147), neurological events (13/147), new-onset or unmasked PNH (10/147), non-meningococcal infection (9/147), rechallenge hemolysis (8/147), thrombosis (8/147), other events (7/147), marrow failure/cytopenia (6/147), and rhabdomyolysis/myonecrosis (6/147). Seven deaths occurred: six from invasive meningococcal disease and one from marrow failure. Eight patients demonstrated recurrent hemolysis after vaccine exposures, including manufacturer-confirmed positive rechallenge, CH50 complement consumption, and complement-inhibitor modulation. Primary hemolysis clustered earlier than breakthrough meningococcal disease (median 12 versus 153 days; Mann-Whitney p = 0.001). Post-hoc VAERS modifications were identified in 62/147 cases (42%); 28 required major archival reconstruction, additional structured fields were restored during physician adjudication from archived records, manufacturer identifiers, published case reports, preserved narratives, and cross-referenced source documents. Conclusions These data support vaccination as a complement-amplifying trigger for hemolytic events in susceptible patients with PNH and identify practical risk-mitigation targets: complement-inhibitor/vaccination sequencing, early post-vaccination hemolysis monitoring, and meningococcal prevention planning during complement blockade. Hematology paroxysmal nocturnal hemoglobinuria PNH VAERS pharmacovigilance complement activation breakthrough hemolysis eculizumab ravulizumab meningococcal vaccine adverse events rechallenge deduplication new-onset PNH platform stratification mRNA vaccine Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9645631","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":637924917,"identity":"b8241e0f-3a6c-46f5-9a53-14993af05a4d","order_by":0,"name":"Robert W. Chandler MD","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYLACngo4U0KGSC1ngAQbRAsPcVp42+BaGAhrMZ+R/HTD23l38vnlm489ulFjwcPAfvjoBnxaZG6kmd2cu+2Z5cw2tnTjnGNAh/Gkpd3Ap0VCOoftNu+2wwYGx3jMgGygFgkeMyK0zIFp+Ue0lgaoltw2YrTIPzO7OefYMwPJtrQ06dw+CR42gn7hOfzsxpuaOwb8zIePSed8q5PjZz98DK8WKDiAYLIRoRxNyygYBaNgFIwCdAAANIRBsppOS40AAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0003-1755-2944","institution":"Independent Researcher, Former Associate Clinical Professor USC and Assistant Clinical Professor, Univeristy Of California Irvine; Retired","correspondingAuthor":true,"prefix":"","firstName":"Robert","middleName":"W.","lastName":"Chandler","suffix":"MD"},{"id":637924918,"identity":"21371cf0-20b0-4872-ac58-3b96b53f906f","order_by":1,"name":"Amy W. 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Vaccination may activate complement inducing hemolysis in PNH patients when given, as recommended by regulatory agencies, before complement-inhibitor therapy is initiated or optimized.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a pharmacovigilance analysis of PNH Vaccine Adverse Event Recording System (VAERS) reports through February 2026. Eighteen PNH-related search terms were applied across seven VAERS fields. Candidate reports underwent physician review, pairwise deduplication, five-tier PNH confirmation, clinical classification, and archival recovery of modified, blanked (absence of VAERS narrative or structured-field content that was present and publicly available in earlier archived versions), or removed records.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 500 candidate reports, 147 unique patient-events met inclusion criteria. Primary hemolysis was the largest category (55/147), followed by breakthrough meningococcal disease (32/147), neurological events (13/147), new-onset or unmasked PNH (10/147), non-meningococcal infection (9/147), rechallenge hemolysis (8/147), thrombosis (8/147), other events (7/147), marrow failure/cytopenia (6/147), and rhabdomyolysis/myonecrosis (6/147). Seven deaths occurred: six from invasive meningococcal disease and one from marrow failure. Eight patients demonstrated recurrent hemolysis after vaccine exposures, including manufacturer-confirmed positive rechallenge, CH50 complement consumption, and complement-inhibitor modulation. Primary hemolysis clustered earlier than breakthrough meningococcal disease (median 12 versus 153 days; Mann-Whitney p\u0026thinsp;=\u0026thinsp;0.001). Post-hoc VAERS modifications were identified in 62/147 cases (42%); 28 required major archival reconstruction, additional structured fields were restored during physician adjudication from archived records, manufacturer identifiers, published case reports, preserved narratives, and cross-referenced source documents.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThese data support vaccination as a complement-amplifying trigger for hemolytic events in susceptible patients with PNH and identify practical risk-mitigation targets: complement-inhibitor/vaccination sequencing, early post-vaccination hemolysis monitoring, and meningococcal prevention planning during complement blockade.\u003c/p\u003e","manuscriptTitle":"Paroxysmal Nocturnal Hemoglobinuria After Vaccination: A Systematic Pharmacovigilance Analysis of 147 Cases","msid":"","msnumber":"","nonDraftVersions":[{"code":2,"date":"2026-05-15 20:01:26","doi":"10.21203/rs.3.rs-9645631/v2","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2026-05-11 05:47:30","doi":"10.21203/rs.3.rs-9645631/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"84ace62f-3283-4307-9b4b-2e63cd5140b6","owner":[],"postedDate":"May 15th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":68200532,"name":"Hematology"}],"tags":[],"updatedAt":"2026-05-11T05:47:30+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-15 20:01:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v2","identity":"rs-9645631","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9645631","identity":"rs-9645631","version":["v2"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}