{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:01:21Z","timestamp":1790596881202,"version":"4.1.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study evaluates the practice of incorporating a saline testing condition into the heparin-induced thrombocytopenia (HIT) functional assay using whole-blood impedance aggregometry (WBIA) to identify a subgroup of highly pathogenic anti\u2013platelet factor 4 (PF4) antibodies with heparin-independent platelet-activating properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From 2023 to 2025, we analyzed 150 evaluable patients (65 WBIA Negative, 85 WBIA Positive). Positive cases were subdivided into Classic-Positive (low-dose heparin positive only; n\u2009=\u200946) and Saline-Positive (positive under both low-dose heparin and saline; n\u2009=\u200935). The diagnosis of clinical HIT by hematologists was used as reference. PF4\/IgG was measured by chemiluminescent immunoassay; WBIA was performed with low-dose heparin, high-dose heparin, and saline; and available serotonin release assay (SRA) results were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Saline-Positive patients exhibited significantly higher incidences of HIT-associated thrombosis (89% vs 54%, P\u2009=\u2009.005), delayed-onset HIT (23% vs 0%, P\u2009=\u2009.001), refractory HIT (40% vs 7%, P &amp;lt; .001), spontaneous HIT (14% vs 0%, P\u2009=\u2009.013), and more venous thromboembolism (pulmonary embolism and deep vein thrombosis, P &amp;lt; .05) compared with Classic-Positive patients. All 35 Saline-Positive cases were classified as autoimmune HIT (aHIT). The spontaneous HIT subset (n\u2009=\u20095) displayed a distinct pattern of low-titer anti-PF4 antibodies discordant with strong saline-WBIA reactivity and a high SRA false-negative rate (57.1%). High-dose intravenous immunoglobulin neutralized saline positivity in real time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Saline-positivity in WBIA identifies a heparin-independent aHIT phenotype with higher pathogenicity and thrombotic risk. This rapid saline protocol addresses diagnostic gaps where standard 2-condition SRA protocols may fail, offering a practical tool to identify high-pathogenic anti-PF4 antibodies and guide clinical management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajcp\/aqag100","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:46:34Z","timestamp":1787139994000},"source":"Crossref","is-referenced-by-count":0,"title":["Saline whole-blood impedance aggregometry for detection of heparin-independent platelet-activating anti\u2013platelet factor 4 antibodies"],"prefix":"10.1093","volume":"166","author":[{"given":"Jing","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Special Coagulation, Clinical Laboratory, Stanford Hospital and Clinics , Stanford, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu M","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Dell Medical School, University of Texas at Austin , Austin, TX,","place":["United States"]},{"name":"Department of Pathology, School of Medicine, Stanford University , Stanford, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People\u2019s Hospital , Chengdu, Sichuan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krinaben","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Special Coagulation, Clinical Laboratory, Stanford Hospital and Clinics , Stanford, CA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Zehnder","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Stanford University , 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