Rapid immunoassays for diagnosis of heparin-induced thrombocytopenia: Comparison of diagnostic accuracy, reproducibility, and costs in clinical practice

Andriyana Bankova; Yvonne Andres; Michael P Horn; Lorenzo Alberio; Michael Nagler

doi:10.1371/journal.pone.0178289

Rapid immunoassays for diagnosis of heparin-induced thrombocytopenia: Comparison of diagnostic accuracy, reproducibility, and costs in clinical practice

PLoS One. 2017 Jun 8;12(6):e0178289. doi: 10.1371/journal.pone.0178289. eCollection 2017.

Authors

Andriyana Bankova¹, Yvonne Andres², Michael P Horn^{3

4}, Lorenzo Alberio^{5

6}, Michael Nagler^{7

8}

Affiliations

¹ Division of Haematology and Central Haematology Laboratory, Luzerner Kantonsspital, Lucerne, Switzerland.
² Kreisspital für das Freiamt, Muri, Switzerland.
³ University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Centre of Laboratory Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁵ Division of Hematology and Central Hematology Laboratory, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
⁶ University of Lausanne, Lausanne, Switzerland.
⁷ Department of Haematology, Inselspital, Bern University Hospital, University of Bern, Berne, Switzerland.
⁸ Department of Clinical Research, University of Bern, Berne, Switzerland.

Abstract

Background: Immunoassays are crucial in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT) and rapid tests have been recently developed. However, comparative data on diagnostic accuracy, reproducibility, and analytical costs of different immunoassays in clinical practice are limited.

Methods: Samples of 179 consecutive patients evaluated for suspected HIT in clinical practice using a polyspecific enzyme-linked immunoabsorbent assay (GTI diagnostics; ELISA) and a rapid particle gel immunoassay (PaGIA), were additionally analysed with a IgG-specific chemiluminescent immunoassay (AcuStar HIT-IgG). Presence of HIT was defined as a positive functional heparin-induced platelet aggregation test. Diagnostic accuracy was determined for low, intermediate and high thresholds as previously established (ELISA: optical density 0.4, 1.3, and 2.0 respectively; PaGIA: positive/negative, titre of 4, titre of 32; AcuStar HIT-IgG: 1.0 U/ml, 2.8, 9.4) and reproducibility was assessed by repeated measurements. Costs of test determination were calculated taking reagents, controls, and working time of technicians according to Swiss health care system into account.

Results: Data on PaGIA results were available for 171 patients (95.5%), ELISA for 144 patients (80.4%), and AcuStar HIT-IgG for 179 patients (100%). Sensitivity was above 95% for all assays at low and intermediate thresholds. Specificity increased with higher thresholds and was above 90% for all assays with intermediate and high thresholds. Specificity of AcuStar HIT-IgG (92.8%; 95% CI 87.7, 96.2) was significantly higher than PaGIA (83.0%; 95% CI 76.3, 88.5) and higher than ELISA (81.8%, 95% CI 74.2, 88.0) at low threshold (p<0.05). Reproducibility was adequate for all assays. Total costs per test were CHF 51.02 for ELISA, 117.70 for AcuStar HIT-IgG, and 83.13 for PaGIA.

Conclusions: We observed favourable diagnostic accuracy measures and a high reproducibility for PaGIA and AcuStar HIT-IgG. Implementation into 24-hours-service might improve patient care but the results must be confirmed in other settings and larger populations as well.

MeSH terms

Enzyme-Linked Immunosorbent Assay
Heparin / toxicity*
Humans
Immunoassay / economics
Immunoassay / methods*
Luminescent Measurements
Sensitivity and Specificity
Thrombocytopenia / blood
Thrombocytopenia / chemically induced*
Thrombocytopenia / diagnosis*

Substances

Heparin

Grants and funding

The costs of the reagents were covered by routine laboratory budget. The authors received no specific funding for this work.