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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Utilize Saline Control in Heparin-Induced Thrombocytopenia Functional Assay To Identify Heparin-Independent Antibodies (THSNA �Travel Awardee) Jing Jin1, Krinaben Patel1, Lu Yang2, James Zehnder2. 1Special Coagulation, Stanford Health Care Palo Alto, CA, USA.2Department of Pathology, School of Medicine, Stanford University, Palo Alto, CA, USA |
Abstract
Background: The routine inclusion of a saline control in our heparin-induced thrombocytopenia (HIT) functional assay using whole blood impedance aggregometry (WBIA) allows for the detection of platelet reactivity in the absence of heparin. Our observations suggest that saline-positivity (reactivity without heparin) is associated with monoclonal gammopathy spontaneous HIT, delayed-onset HIT, and refractory HIT, presenting with more severe prothrombotic manifestations. Objectives: This study aims to validate the practice of incorporating a saline control in HIT functional assays to identify a subgroup of highly pathogenic anti-PF4 antibodies with heparin-independent platelet-activating properties. Methods: From January 2023 to July 2025, we analyzed 182 consecutive samples from 155 patients tested with the WBIA, which is performed as a reflex test when HIT PF4/IgG is positive, though occasionally ordered directly. Among these patients, 83 (53.5%) tested positive by WBIA. After excluding 5 patients due to unavailable chart reviews and 1 patient whose sample was contaminated with epinephrine from line fluid, we categorized the remaining 77 positive patients into three groups: Classic-Positive (43 patients, 55.8%), who tested positive under low-dose heparin but negative under high-dose heparin and saline; Saline-Positive (30 patients, 40.3%), who tested positive under both low-dose heparin and saline, further confirmed by an anti-Xa activity of <0.05 IU/ml to rule out residual heparin effects; and High-Dose Heparin Positive (4 patients), who tested positive under both low and high-dose heparin but negative under saline. The diagnosis of Clinical HIT served as the reference for the HIT functional assay, evaluated by experienced hematologists based on clinical and laboratory criteria. We analyzed concurrent PF4/IgG antibody results, platelet aggregation percentages under low-dose heparin, high-dose heparin, and saline via WBIA, as well as serotonin release assay (SRA) results when available. Chart reviews focused on the presence and severity of HIT-associated thrombosis, monoclonal gammopathy, delayed-onset HIT, refractory HIT, and 30-day all-cause mortality. Results: In this study, WBIA had 87.5% sensitivity and 83.3% specificity, with results not statistically different from SRA, which had 66.7% sensitivity and 94.4% specificity (n=42, P >0.05). Notably, saline-positivity was frequently observed in WBIA (21.4% of all studied samples), compared to 29.7% for Classic-Positivity. All 30 patients classified in “Saline-Positive “ group were confirmed as having clinical HIT, exhibiting a significantly higher incidence of delayed-onset HIT (20%), refractory HIT (30%), pulmonary embolism (37%), deep vein thrombosis (57%), and HIT-associated thrombosis (83%), compared to the “Classic-Positive” group (p-values <0.05). Conclusions : The presence of saline-positivity in HIT functional assay may indicate a higher pathogenicity of HIT antibodies, characterized by an increased frequency of HIT-associated thrombotic complications. Incorporating a saline control in HIT functional assays helps isolate the effects of heparin-independent antibodies, clarifying their nature and guiding clinical treatment strategies, such as the addition of intravenous immunoglobulin (IVIG) and rituximab, alongside the discontinuation of heparin. Our in-house WBIA is a simple, rapid and reliable HIT functional assay that seamlessly integrates this additional saline testing.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.