Hamostaseologie 2025; 45(S 01): S36
DOI: 10.1055/s-0044-1801596
Abstracts
Topics
T-06 Diagnostics and laboratory tests

The dynamic range of immunoassays for heparin-induced thrombocytopenia

Authors

  • H Nilius

    1   Inselspital University Hospital Bern, Department of Clinical Chemistry, Bern, Switzerland
    2   University of Bern, Graduate School for Health Sciencesuat, Bern, Switzerland

  • S Naas

    1   Inselspital University Hospital Bern, Department of Clinical Chemistry, Bern, Switzerland

  • J-D Studt

    3   University and University Hospital Zurich, Division of Medical Oncology and Hematology, Zürich, Switzerland

  • D A Tsakiris

    4   Basel University Hospital, Department of Haematology, Basel, Switzerland

  • A Greinacher

    5   Universitätsmedizin Greifswald, Institut für Immunologie und Transfusionsmedizin, Greifswald, Germany

  • A Mendez

    6   Kantonsspital Aarau, Institute of Laboratory Medicine, Aarau, Switzerland

  • A Schmidt

    7   Municipal Hospital Zurich Triemli, Institute of Laboratory Medicine and Clinic of Medical Oncology and Hematology, Zürich, Switzerland

  • W A Wuillemin

    8   Cantonal Hospital of Lucerne and University of Bern, Division of Hematology and Central Hematology Laboratory, Lucerne, Switzerland

  • B Gerber

    9   Oncology Institute of Southern Switzerland, Clinic of Hematology, Bellinzona, Switzerland

  • P Vishnu

    10   University of Washington, Fred Hutchinson Cancer Center, Division of Hematology, Seattle, USA

  • L Graf

    11   Cantonal Hospital of St Gallen, St Gallen, Switzerland

  • J A Kremer Hovinga

    12   Inselspital Bern University Hospital, Department of Hematology and Central Hematology Laboratory, Bern, Switzerland

  • T Bakchoul

    13   University Hospital of Tübingen, Centre for Clinical Transfusion Medicine, Tübingen, Germany

  • C Nakas

    1   Inselspital University Hospital Bern, Department of Clinical Chemistry, Bern, Switzerland
    14   University of Thessaly, Laboratory of Biometry, School of Agriculture, Volos, Greece

  • M Nagler

    1   Inselspital University Hospital Bern, Department of Clinical Chemistry, Bern, Switzerland
    15   University of Bern, Bern, Switzerland
Further Information
Also available at
 
 

    Introduction: Following the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted in a dichotomous manner, categorizing test results as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear.

    Method: We utilized data from the prospective TORADI-HIT study, comprising 1393 consecutive patients with suspected HIT, to assess the diagnostic significance of three H/PF4 -immunoassay test results across their respective dynamic ranges (HemoSil Acustar HIT IgG [CLIA], Lifecodes PF4 IgG [ELISA], Diamed ID H-PF4 [PaGIA]). The diagnosis of HIT was determined by a washed-platelet heparin-induced platelet activation assay (HIPA). For each measurement point in the dataset, we computed likelihood ratios (LR), sensitivities, and specificities.

    Results: The prevalence of HIT was 8.5% (n=119). A likelihood ratio of≥10 was first achieved at 0.3% of the dynamic range (0.4 U/ml; CLIA), 16% (0.64 OD; ELISA), and 1.6% (1:4 titre; PaGIA), respectively. A likelihood ratio of≥100 was present at 9.4% (12 U/ml; CLIA), 75.0% (3.0 OD; ELISA), 25.0% (1:64 titre; PaGIA), respectively. The slope of the linear regression line (LR ~ dynamic range) was 9.5 (CLIA), 0.9 (ELISA), and 4.6 (PaGIA). To provide post-test probabilities for individual test results, we calculated interval-specific likelihood ratios and integrated it into a web-based calculator (https://pcd-research.shinyapps.io/BayesianCalculator/).

    Conclusion: In conclusion, despite all immunoassays demonstrating an association between diagnostic significance and results, the strength of that association varies with the assay, with the CLIA having the largest increase per measurement unit.


     

    Conflict of Interest:

    The institution of JKH received grant support, consultancy fees, or honoraria from SNSF, Baxter/Takeda, Bayer, CSL-Behring, NovoNordisk, Octapharma, Roche, SOBI, Roche, Sanofi, FOPH, and Swiss Hemophilia Society, outside of the current work. MN received research grants from Bayer Healthcare, Roche diagnostics, Siemens healthineers, Pentapharm, and Bühlmann laboratories, as well as lecture fees from Sysmex, Siemens healthineers, and Euroimmun, Viatris, outside of the current work. JDS received lecture and advisory board honoraria from Bayer, CSL Behring, Pfizer, Sanofi, Siemens Diagnostics, Sobi, Takeda (all unrelated to the current work). AG reports personal fees from Aspen, grants from Ergomed, grants from Boehringer Ingelheim, personal fees from Bayer Vital, grants from Rovi, grants from Sagent, personal fees from Chromatec, personal fees from Instrumentation Laboratory, grants and personal fees from Macopharma, grants from Portola, grants from Biokit, personal fees from Sanofi-Aventis, grants from Blau Farmaceutics, grants from Prosensa/Biomarin, grants and other from DRK-BSD NSTOB, grants from DRK-BSD Baden-Würtemberg/Hessen, personal fees from Roche, personal fees from GTH e.V., grants from Deutsche Forschungsgemeinschaft, grants from Robert-Koch-Institut, non-financial support from Veralox, personal fees from Dilaflor, non-financial support from Vakzine Projekt Management GmbH, grants from GIZ Else-Körner-Stiftung, non-financial support from AstraZeneca, non-financial support from Janssen Vaccines & Prevention B.V., personal fees from Takeda Pharma, personal fees from Falk Foundation e.V., grants from European Medicines Agency , personal fees from Mylan Germany, outside the submitted work; In addition, Dr. Greinacher has a patent Screening Methods for transfusion related acute lung injury (TRALI) with royalties paid to EP2321644, 18.05.2011 , and a patent Verfahren und Vorrichtung zur Herstellung von Universalplasma. licensed to DE 10 2020 212 609 B3 2022.04.07. TB reports grant support, consultancy fees, honoraria, or support for attending meetings from DFG, Stiftung Transfusionsmedizin und Immunhämatologie e.V, DRK Blutspendedienst, Deutsche Herzstiftung, Ministerium für Wissenschaft, Forschung und Kunst Baden Würtemberg, Gesellschaft für Thrombose- und Hämostaseforschung, Berufsverband Deutscher Internisten, CoaChrom Diagnostica GmbH, Robert Bosch GmbH, Ergomed, Bayer, Bristol-Myers Squibb, Doctrina Med AG, Leo Pharma GmbH, Schöchl medical education GmbH, Mitsubishi Tanabe GmbH, Novo Nordisk GmbH, Swedish Orphan Biovitrium GmbH. All other authors declare that no conflict of interest exists.

    Publication History

    Article published online:
    13 February 2025

    © 2025. Thieme. All rights reserved.

    Georg Thieme Verlag KG
    Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany