Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study

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

doi:10.1016/j.jtha.2023.05.016

Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study

J Thromb Haemost. 2023 Sep;21(9):2559-2568. doi: 10.1016/j.jtha.2023.05.016. Epub 2023 May 27.

Authors

Affiliations

¹ Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
² Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Division of Medical Oncology and Hematology, University and University Hospital Zurich, Zurich, Switzerland.
⁴ Diagnostic Haematology, Basel University Hospital, Basel, Switzerland.
⁵ Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany.
⁶ Institute of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
⁷ 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, Bern, Switzerland.
⁹ Clinic of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
¹⁰ Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹¹ Division of Hematology, CHI Franciscan Medical Group, Seattle, USA.
¹² Cantonal Hospital of St. Gallen, St. Gallen, Switzerland.
¹³ Centre for Clinical Transfusion Medicine, University Hospital of Tübingen, Tübingen, Germany.
¹⁴ Department of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: michael.nagler@insel.ch.

PMID: 37247669
DOI: 10.1016/j.jtha.2023.05.016

Abstract

Background: Anecdotal reports suggest that the correlation between heparin/platelet factor 4 (PF4) antibody assays for the diagnosis of heparin-induced thrombocytopenia (HIT) is limited.

Objectives: To investigate the correlation between widely used assays and examine possible factors contributing to variability.

Methods: This is a large, prospective cohort study with 10 participating tertiary care hospitals including 1393 patients with suspected HIT in clinical practice. HIT was defined by a positive heparin-induced platelet activation (HIPA) assay (washed platelet reference standard test). Three different immunoassays were used to measure heparin/PF4 antibodies: chemiluminescent immunoassay, enzyme-linked immunosorbent assay, and particle gel immunoassay. Various factors that could influence the assays were examined: sex (male or female), age (<65 years or ≥65 years), unfractionated heparin exposure, presence of thrombosis, cardiovascular surgery, and intensive care unit. Spearman's correlation coefficients were calculated. Z-scores and diagnostic odds ratios were determined in the aforementioned subgroups of patients.

Results: Among 1393 patients, 119 were classified as HIT-positive (prevalence, 8.5%). The median 4Ts score was 5 (IQR, 4-6) in patients with HIT compared with 3 (IQR, 2-4) in patients without HIT. Correlations (r_s) between immunoassays were weak (0.53-0.65). Inconsistencies between immunoassays could not be explained by further analyses of z-scored test results and diagnostic odds ratios in subgroups of patients.

Conclusion: The correlation between widely used heparin/PF4 antibody assays was weak, and key factors could not explain this variability. Standardization of immunoassays is requested to improve comparability.

Keywords: contributing factors; correlation; diagnostic odds ratio; heparin-induced platelet activation assay; heparin-induced thrombocytopenia; heparin/PF4 antibody assays.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies
Anticoagulants / adverse effects
Female
Heparin* / adverse effects
Humans
Male
Platelet Factor 4
Prospective Studies
Thrombocytopenia* / chemically induced
Thrombocytopenia* / diagnosis

Substances

Heparin
Platelet Factor 4
Antibodies
Anticoagulants