Presentation Details
| Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia Using Two Combined Rapid Automated Assays Anna-Lise Bissola1, 2, Yi Zhang1, 3, Madison Cranstone2, 4, Donald Arnold1, 2, Ishac Nazy1, 2. 11.Faculty of Medicine, Michael DeGroote School of Medicine, McMaster University, 2.Michael G.DeGroote Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada.2Faculty of Medicine, Michael DeGroote School of Medicine, McMaster University, 3.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.32.Michael G.DeGroote Centre for Transfusion Research, McMaster University, 4.Department of Statistics and Actuarial Science, University of Waterloo, Hamilton, ON, Canada.41.Faculty of Medicine, Michael DeGroote School of Medicine, McMaster University, 2.Michael G.DeGroote Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada.51.Faculty of Medicine, Michael DeGroote School of Medicine, McMaster University, 2.Michael G.DeGroote Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada |
Abstract
Background: Most diagnostic laboratory enzyme immunoassays (EIA) for heparin-induced thrombocytopenia (HIT) are excellent for ‘ruling-out’ HIT but suffer from reduced specificities. Alternatively, functional platelet-activation assays, including the 14C-serotonin release assay (SRA), offer higher specificity and sensitivity, but are technically challenging and require healthy donor platelets. Rapid automated assays may offer a solution to these diagnostic challenges. However, further practical evaluations of these assays are required. Aims: This study compared the performances of latex immunoturbidimetric assay (LIA) and chemiluminescence immunoassay (CLIA), either alone or in combination, to identify the presence of platelet-activating anti-PF4/heparin antibodies in a prospective cohort of clinically suspected HIT patients. Moreover, we compared the performance of two algorithmic approaches developed in previous retrospective studies that evaluate the combined performance of both automated assays. Methods: A total of 1144 unique patient serum or plasma samples were collected between December 2018 and August 2020 based on a clinical suspicion of HIT. Based on sample availability, patients were tested in a commercial Immucor IgG/A/M PF4-enhanced EIA (IgG/A/M EIA, n=914), LIA (HemosIL®HIT-Ab(PF4-H)], n=1012), CLIA ([HemosIL®AcuStarHIT-Ab(PF4-H)], n=1128), or both LIA and CLIA (n=996) according to manufacturer's instructions. The combined performance of the LIA and CLIA (n=996) was determined by using two previously evaluated test algorithms 1) the Simultaneous approach adapted from Warkentin et al.1 and 2) the Sequential approach adapted from Rittener-Ruff et al.2 Using the Simultaneous algorithm, patients are tested in both rapid assays and a positive result is obtained where CLIA and/or LIA results are ≥ 1.0 U/mL. Using the Sequential algorithm, LIA testing combined with an “assumed” high (6-8) or intermediate (4-5) 4T scores was used to predict or exclude HIT, followed by CLIA testing where results were inconclusive. Following CLIA testing, HIT was again predicted or excluded using 4T scores. Patients who remain inconclusive when using 4Ts scores and LIA/CLIA results are resolved with additional testing in a functional platelet-activation assay (SRA). Results: Using the standard SRA as a surrogate reference for the confirmation of HIT, we determined the performance characteristics of the IgG/A/M EIA (sensitivity 100%, specificity 48.6%), LIA (sensitivity 91.7%, specificity 68.4%), CLIA (sensitivity 92.4%, specificity 85.8%), and combined CLIA-LIA using the Simultaneous algorithm1 (sensitivity 99.0%, specificity 64.3%). The Sequential algorithm2 assuming intermediate (4-5) or high (6-8) 4T scores correctly predicted HIT in 94.5% and 96.0% of patients and correctly excluded HIT in 82.6% and 80.1% of patients, respectively. Conclusion: Compared to individual LIA or CLIA testing, both combined algorithms improved diagnostic performance, supporting the use of these assays together for HIT diagnosis to supplement platelet-activation assays if both instruments are available. Evaluating two diagnostic strategies using a single cohort of prospective patients revealed the Simultaneous algorithm to have a lower number of false HIT predictions (7.9%) than the Sequential algorithm (37.6% and 41.6%). We also found the Simultaneous algorithm more practical because it does not rely on 4T scores. Our work also highlights that prospective studies accounting for clinician and interlaboratory variability can more accurately evaluate the real-world performance of HIT diagnostic tests.
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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.
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