Integrating HLA and HPA for Precision Transfusion: Anti-CD36–Mediated Refractoriness and Hemostatic Challenges

Integrating HLA and HPA in Precision Transfusion: Insights from Platelet Transfusion Refractoriness Driven by Anti-CD36 Alloimmunization and Multifactorial Hemostatic Complications | 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 Integrating HLA and HPA in Precision Transfusion: Insights from Platelet Transfusion Refractoriness Driven by Anti-CD36 Alloimmunization and Multifactorial Hemostatic Complications Shin-Yi Tsai, Kuan-Hsiao Lin, Sheng-Mou Hou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7551923/v3 This work is licensed under a CC BY 4.0 License Status: Posted Version 3 posted You are reading this latest preprint version Show more versions Abstract Purpose: CD36, recognized as a distinct blood group system, encodes a class-B scavenger receptor essential for hemostasis and innate immunity. Alloantibodies against CD36, although often overlooked, are a significant cause of platelet transfusion refractoriness (PTR), fetal–neonatal alloimmune thrombocytopenia, and immune-mediated bleeding. The comparative effectiveness of platelet antibody assays remains unclear. We aim to propose a streamlined diagnostic algorithm for PTR. Methods: This retrospective cohort study, conducted at a tertiary center, analyzed 2,453 patients undergoing parallel screening for platelet antibodies using both the Solid Phase Red Cell Adherence Assay (SPRCA) and qualitative ELISA over a period of nearly seven years. Confirmatory workflows included MAIPA, molecular genotyping, and flow cytometry for CD36 antigen expression. Six illustrative cases with genetically or phenotypically confirmed CD36 deficiency were comprehensively profiled. Results: ELISA detected antiplatelet antibodies in 33.5% of samples, while SPRCA identified them in 18.1%, yielding a moderate overall concordance of 78.1% (κ = 0.444). Among SPRCA-positive samples, 81.9% were confirmed by ELISA; for SPRCA-negatives, 22.8% were ELISA-positive, underscoring substantial assay discordance. Notably, 18.7% of cases were exclusively ELISA-positive, compared to only 3.3% detected solely by SPRCA. Dual assay positivity was highly specific for clinically significant platelet alloimmunization and PTR. Conclusion: Our findings highlight the critical role of combined ELISA and SPRCA screening, supplemented by confirmatory and molecular methods, in accurately identifying anti-CD36 alloimmunization. The study underscores the need for comprehensive diagnostic protocols, rare donor registry development and the broader implementation of CD36-negative platelet inventories to optimize personalized transfusion strategies and patient outcomes. Molecular Genetics Immunology Internal Medicine Hematology Cancer Biology CD36 deficiency CD36 alloimmunization platelet transfusion refractoriness Monoclonal Antibody-specific Immobilization of Platelet Antigens(MAIPA) Solid Phase Red Cell Adherence Assay(SPRCA) Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 3 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. 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Complications","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"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},"keywords":"CD36 deficiency, CD36 alloimmunization, platelet transfusion refractoriness, Monoclonal Antibody-specific Immobilization of Platelet Antigens(MAIPA), Solid Phase Red Cell Adherence Assay(SPRCA)","lastPublishedDoi":"10.21203/rs.3.rs-7551923/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7551923/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e CD36, recognized as a distinct blood group system, encodes a class-B scavenger receptor essential for hemostasis and innate immunity. Alloantibodies against CD36, although often overlooked, are a significant cause of platelet transfusion refractoriness (PTR), fetal–neonatal alloimmune thrombocytopenia, and immune-mediated bleeding. The comparative effectiveness of platelet antibody assays remains unclear. We aim to propose a streamlined diagnostic algorithm for PTR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis retrospective cohort study, conducted at a tertiary center, analyzed 2,453 patients undergoing parallel screening for platelet antibodies using both the Solid Phase Red Cell Adherence Assay (SPRCA) and qualitative ELISA over a period of nearly seven years. Confirmatory workflows included MAIPA, molecular genotyping, and flow cytometry for CD36 antigen expression. Six illustrative cases with genetically or phenotypically confirmed CD36 deficiency were comprehensively profiled.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eELISA detected antiplatelet antibodies in 33.5% of samples, while SPRCA identified them in 18.1%, yielding a moderate overall concordance of 78.1% (κ = 0.444). Among SPRCA-positive samples, 81.9% were confirmed by ELISA; for SPRCA-negatives, 22.8% were ELISA-positive, underscoring substantial assay discordance. Notably, 18.7% of cases were exclusively ELISA-positive, compared to only 3.3% detected solely by SPRCA. Dual assay positivity was highly specific for clinically significant platelet alloimmunization and PTR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eOur findings highlight the critical role of combined ELISA and SPRCA screening, supplemented by confirmatory and molecular methods, in accurately identifying anti-CD36 alloimmunization. The study underscores the need for comprehensive diagnostic protocols, rare donor registry development and the broader implementation of CD36-negative platelet inventories to optimize personalized transfusion strategies and patient outcomes.\u003c/p\u003e","manuscriptTitle":"Integrating HLA and HPA in Precision Transfusion: Insights from Platelet Transfusion Refractoriness Driven by Anti-CD36 Alloimmunization and Multifactorial Hemostatic Complications","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2025-11-19 20:20:03","doi":"10.21203/rs.3.rs-7551923/v3","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":2,"date":"2025-09-30 17:16:35","doi":"10.21203/rs.3.rs-7551923/v2","editorialEvents":[{"type":"communityComments","content":1}],"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":"2025-09-22 10:06:15","doi":"10.21203/rs.3.rs-7551923/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":"2caaef46-ef33-4e51-b44c-fb27c64555d4","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":55595884,"name":"Molecular Genetics"},{"id":55595885,"name":"Immunology"},{"id":55595886,"name":"Internal Medicine"},{"id":55595887,"name":"Hematology"},{"id":55595888,"name":"Cancer Biology"}],"tags":[],"updatedAt":"2025-10-27T18:28:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 20:20:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v3","identity":"rs-7551923","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7551923","identity":"rs-7551923","version":["v3"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}