{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T09:44:04Z","timestamp":1779011044214,"version":"3.51.4"},"reference-count":44,"publisher":"American Society of Hematology","issue":"25","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,6,19]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Heparin-induced thrombocytopenia (HIT) is initiated by antibodies that recognize large antigenic complexes composed of multiple molecules of cationic platelet factor 4 (PF4) and polyanions such as unfractionated heparin (UFH) that bind to each other primarily through electrostatic interactions. We asked whether the formation and stability of these HIT antigenic or ultralarge immune complexes (ULICs) would be inhibited by biocompatible synthetic polycationic molecules shown previously to dissociate UFH from antithrombin III and to inhibit polyphosphates. Members of this family of molecules, designated universal heparin reversal agents (UHRAs), inhibited formation and dissociated preformed ultralarge PF4-UFH (antigenic) complexes (ULCs), dissociated ULICs composed of the HIT-like monoclonal antibody KKO and ULCs, blocked binding of human HIT immunoglobulin G antibodies to PF4\/heparin, binding of KKO to platelets, KKO-induced adhesion of platelets to activated human endothelium under flow, and microvascular thrombosis induced by KKO in a mouse model of HIT. These data suggest that UHRAs might provide a rationale intervention that acts at an early step in the pathogenesis of HIT to enhance the benefits and lessen the risks of nonheparin anticoagulants. Destabilization of immune complexes using polycationic inhibitors might also find a role in management of other polyanion PF4-antibody\u2013mediated conditions, including vaccine-induced thrombocytopenia\/thrombosis, postviral, and autoimmune HIT.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025653","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T02:23:16Z","timestamp":1742955796000},"page":"3030-3040","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":9,"title":["Destabilization of PF4-antigenic complexes in heparin-induced thrombocytopenia"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1990-3077","authenticated-orcid":false,"given":"Lubica","family":"Rauova","sequence":"first","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"},{"name":"2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-4036","authenticated-orcid":false,"given":"Khalil","family":"Bdeir","sequence":"additional","affiliation":[{"name":"3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7363-5379","authenticated-orcid":false,"given":"Ann H.","family":"Rux","sequence":"additional","affiliation":[{"name":"3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manu Thomas","family":"Kalathottukaren","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Center for Blood Research and Life Sciences Institute, The University of British Columbia, Vancouver, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5246-2278","authenticated-orcid":false,"given":"Jenna","family":"Oberg","sequence":"additional","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7962-7759","authenticated-orcid":false,"given":"Chanel C.","family":"La","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Center for Blood Research and Life Sciences Institute, The University of British Columbia, Vancouver, Canada"},{"name":"5Department of Chemistry, The University of British Columbia, Vancouver, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T. E.","family":"Lim","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Center for Blood Research and Life Sciences Institute, The University of British Columbia, Vancouver, Canada"},{"name":"5Department of Chemistry, The University of British Columbia, Vancouver, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Hayes","sequence":"additional","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin T.","family":"Koma","sequence":"additional","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5828-9682","authenticated-orcid":false,"given":"Amrita","family":"Sarkar","sequence":"additional","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mortimer","family":"Poncz","sequence":"additional","affiliation":[{"name":"1Hematology Division, Children\u2019s Hospital of Philadelphia, Philadelphia, PA"},{"name":"2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7688-7574","authenticated-orcid":false,"given":"Jayachandran N.","family":"Kizhakkedathu","sequence":"additional","affiliation":[{"name":"4Department of Pathology and Laboratory Medicine, Center for Blood Research and Life Sciences Institute, The University of British Columbia, Vancouver, Canada"},{"name":"5Department of Chemistry, The University of British Columbia, Vancouver, Canada"},{"name":"6The School of Biomedical Engineering, The University of British Columbia, Vancouver, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-504X","authenticated-orcid":false,"given":"Douglas B.","family":"Cines","sequence":"additional","affiliation":[{"name":"3Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"7Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"issue":"3","key":"2025061911213132400_bib1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMcp1411910","article-title":"CLINICAL PRACTICE. 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