Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia using Two Combined Automated Rapid Immunoassays

Anna-Lise Bissola; Yi Zhang; Madison Cranstone; Jane C. Moore; Theodore E. Warkentin; Donald M. Arnold; Ishac Nazy

doi:10.1055/s-0044-1786749

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2024; 50(08): 1123-1130
DOI: 10.1055/s-0044-1786749

Review Article

Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia using Two Combined Automated Rapid Immunoassays

Anna-Lise Bissola

¹Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

,

Yi Zhang

¹Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

³Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada

,

Madison Cranstone

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

⁴Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada

,

Jane C. Moore

¹Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

,

Theodore E. Warkentin

⁵Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

⁶Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, Hamilton, Ontario, Canada

,

Donald M. Arnold

¹Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

,

Ishac Nazy

¹Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

²Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada

³Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada

› Institutsangaben

Abstract

Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder caused by antibodies against platelet factor 4 (PF4) and heparin complexes. Rapid immunoassays (IAs) for detection of these antibodies mark a milestone in HIT diagnosis, despite a higher false-positive rate compared with functional platelet-activation assays. However, combining different rapid IAs may help to improve their diagnostic specificity. Here, we compared the individual performance of the latex immunoturbidimetric assay (LIA; HemosIL HIT-Ab [PF4-H]; sensitivity 91.7%, specificity 68.4%) and chemiluminescence immunoassay (CLIA; HemosIL AcuStarHIT-Ab [PF4-H]; sensitivity 92.4%, specificity 85.8%) with their combined performance using two unique diagnostic algorithms in a single prospective cohort of suspected HIT patients. Using the simultaneous algorithm adapted from Warkentin et al, the combined LIA–CLIA had a sensitivity of 99.0% and specificity of 64.3%. The sequential algorithm adapted from Rittener-Ruff et al was applied in two theoretical scenarios to reflect real-world circumstances in diagnostic laboratories where access to clinical information is limited: (1) assuming all patients had an intermediate 4Ts score and (2) assuming all patients had a high 4Ts score. This algorithm correctly predicted HIT in 94.5% (high 4Ts) and 96.0% (intermediate 4Ts) and excluded HIT in 82.6% (high 4Ts) and 80.1% (intermediate 4Ts) of patients in either scenario, respectively. Although both combined algorithms improved diagnostic performance of individual IAs, the simultaneous algorithm showed fewer false predictions (7.9%) than the sequential algorithm (intermediate 4Ts: 37.6% and high 4Ts: 41.5%) and proved more practical as it does not rely on physician evaluations. Our findings highlight the importance of accounting for clinician and interlaboratory variability when evaluating diagnostic tests for HIT.

Keywords

heparin-induced thrombocytopenia - platelet factor 4 - thrombosis - antibodies - laboratory diagnostics

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Referenzen

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