{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:01:57Z","timestamp":1789794117269,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Bleeding in Gaucher disease (GD) is not fully explained by thrombocytopenia and coagulation disorders. Previous studies have shown impaired agonist-induced cluster of differentiation (CD) 62P (CD62P\/P-selectin) responses, but their persistence over time is unknown. This retrospective longitudinal observational study characterized platelet activation and secretion responses over time and factors associated with persistent abnormalities. Whole-blood flow cytometry studies from 333 patients with GD with at least two assessments were analyzed. Platelet activation complex-1 (PAC1), CD62P, and CD63 responses were categorized longitudinally. Patients contributed 949 visits over a median follow-up of 2.3 years. Persistent CD62P abnormality was most frequent (92\/333, 27.6%), compared with PAC1 (45\/329, 13.7%) and CD63 (9\/328, 2.7%). PAC1 abnormalities were more often dynamic, whereas CD62P abnormalities were frequent and persistent, most often involving thrombin receptor-activating peptide 6 (TRAP-6) and cross-linked collagen-related peptide (CRP-XL). Lower platelet count was independently associated with persistent CD62P abnormality, although approximately half of affected patients had platelet counts \u2265150 \u00d7 109\/L. Treatment throughout follow-up was associated with lower odds of persistent CD62P and CD63 abnormalities. Impaired CD62P expression was the predominant persistent abnormality, consistent with preferential impairment of \u03b1-granule secretion. Platelet function changed over time, supporting reassessment in patients with bleeding manifestations and before procedures when previous testing is remote or clinical status has changed.<\/jats:p>","DOI":"10.3390\/ijms27188263","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"8263","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired \u03b1-Granule Secretion Dominates Longitudinal Agonist-Induced Platelet Dysfunction in Gaucher Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9151-0337","authenticated-orcid":false,"given":"Shoshana","family":"Revel-Vilk","sequence":"first","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-8608","authenticated-orcid":false,"given":"Ari","family":"Zimran","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112002, Israel"},{"name":"Agyany Pharma Ltd., Jerusalem 9695614, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tama","family":"Dinur","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3398-7584","authenticated-orcid":false,"given":"Dafna","family":"Frydman","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2088-0422","authenticated-orcid":false,"given":"Elena","family":"Shulman","sequence":"additional","affiliation":[{"name":"Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Benayoun","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eti","family":"Broide","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Naamad","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nechama","family":"Koren","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Saltsman","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/17446651.2018.1445524","article-title":"Recent advances in the diagnosis and management of Gaucher disease","volume":"13","author":"Gary","year":"2018","journal-title":"Expert. 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