The dynamic range of immunoassays for heparin-induced thrombocytopenia

Henning Nilius; Samra Naas; Jan-Dirk Studt; Dimitrios A Tsakiris; Andreas Greinacher; Adriana Mendez; Adrian Schmidt; Walter A Wuillemin; Bernhard Gerber; Prakash Vishnu; Lukas Graf; Johanna A Kremer Hovinga; Tamam Bakchoul; Christos Nakas; Michael Nagler

doi:10.1016/j.jtha.2024.10.026

The dynamic range of immunoassays for heparin-induced thrombocytopenia

J Thromb Haemost. 2024 Nov 12:S1538-7836(24)00642-1. doi: 10.1016/j.jtha.2024.10.026. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Chemistry, Inselspital University Hospital Bern, Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
² Department of Clinical Chemistry, Inselspital University Hospital Bern, Bern, Switzerland.
³ Division of Medical Oncology and Hematology, University of Zurich, University Hospital Zurich, Zurich, Switzerland.
⁴ Department of Haematology, Basel University Hospital, Basel, Switzerland.
⁵ Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
⁶ Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
⁷ Institute of Laboratory Medicine and Clinic of Medical Oncology and Hematology, Municipal Hospital Zurich Triemli, Zurich, Switzerland.
⁸ Division of Hematology and Central Hematology Laboratory, Cantonal Hospital of Lucerne, University of Bern, Lucerne, Switzerland.
⁹ Clinic of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
¹⁰ Division of Hematology, Fred Hutchinson Cancer Center, University of Washington, Seattle, Washington, USA.
¹¹ Cantonal Hospital of St Gallen, St Gallen, Switzerland.
¹² Department of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital, Bern, Switzerland.
¹³ Centre for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany.
¹⁴ Department of Clinical Chemistry, Inselspital University Hospital Bern, Bern, Switzerland; Laboratory of Biometry, School of Agriculture, University of Thessaly, Volos, Greece.
¹⁵ Department of Clinical Chemistry, Inselspital University Hospital Bern, Bern, Switzerland; Faculty of Medicine, University of Bern, Bern, Switzerland. Electronic address: [email protected].

PMID: 39536820
DOI: 10.1016/j.jtha.2024.10.026

Abstract

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

Objectives: We utilized data from the prospective towards precise and rapid diagnosis of heparin-induced thrombocytopenia study, comprising 1393 consecutive patients with suspected HIT, to assess the diagnostic significance of 2 heparin/platelet factor 4 immunoassay test results across their respective dynamic ranges: HemoSil Acustar HIT IgG (chemiluminescence immunoassay [CLIA]) and Lifecodes PF4 immunoglobulin G (enzyme-linked immunosorbent assay [ELISA]).

Methods: HIT diagnosis was determined by a washed platelet heparin-induced platelet activation assay. For each measurement point in the dataset, we computed likelihood ratios (LRs), sensitivities, and specificities. To provide posttest probabilities for individual test results, we calculated interval-specific LRs and integrated them into a web-based calculator.

Results: The prevalence of HIT was 8.5% (n = 119). An LR of ≥10 was first achieved at 0.3% of the dynamic range (0.4 U/mL; CLIA) and then at 16% (0.64 optical density; ELISA). An LR of ≥100 was present at 9.4% (12 U/mL; CLIA) and 75.0% (3.0 optical density; ELISA). The slope of the linear regression line (LR ∼ dynamic range) was 9.5 (CLIA) and 0.9 (ELISA).

Conclusion: Despite both immunoassays showing an association between results and diagnostic significance, the strength of the association varies by assay. CLIA has a larger increase per measurement unit. Posttest probabilities for individual patients can be estimated using a web-based calculator: https://pcd-research.shinyapps.io/BayesianCalculator/.

Keywords: diagnosis; heparin/adverse effects; immunoassay/methods; likelihood functions; platelet factor 4; sensitivity and specificity; thrombocytopenia/diagnosis.