Deep vein thrombosis and pulmonary embolism: a prospective, observational study to evaluate diagnostic performance of the Tina-quant D-Dimer Gen.2 assay

Thomas Bertsch; Wilhelm Behringer; Sabine Blaschke; Richard Body; Simon Davidson; Mirco Müller-Olling; Ge Guo; Anna Rieger; Annika Wahl; Daniel Horner; Yuli Sun; Lucia Turnes; Ulrich Sonner; Michael Hoffmann

doi:10.3389/fcvm.2023.1142465

Deep vein thrombosis and pulmonary embolism: a prospective, observational study to evaluate diagnostic performance of the Tina-quant D-Dimer Gen.2 assay

Front Cardiovasc Med. 2023 Dec 18:10:1142465. doi: 10.3389/fcvm.2023.1142465. eCollection 2023.

Authors

Thomas Bertsch¹, Wilhelm Behringer², Sabine Blaschke³, Richard Body^{4

5}, Simon Davidson⁶, Mirco Müller-Olling⁷, Ge Guo⁸, Anna Rieger⁹, Annika Wahl⁹, Daniel Horner^{10

11}, Yuli Sun⁹, Lucia Turnes¹², Ulrich Sonner¹², Michael Hoffmann⁹

Affiliations

¹ Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany.
² Department of Emergency Medicine, Faculty of Medicine, University of Jena, Jena, Germany.
³ Emergency Department, University Medical Center Göttingen, Göttingen, Germany.
⁴ Division of Cardiovascular Sciences, Core Technology Facility, University of Manchester, Manchester, United Kingdom.
⁵ Emergency Department, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
⁶ Roche Diagnostics International Ltd, Rotkreuz, Switzerland.
⁷ Roche Diagnostics GmbH, Mannheim, Germany.
⁸ Roche Diagnostics, Indianapolis, IN, United States.
⁹ Roche Diagnostics GmbH, Penzberg, Germany.
¹⁰ Emergency Department, Salford Royal NHS Foundation Trust, Salford, United Kingdom.
¹¹ Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, United Kingdom.
¹² Agent Representing Roche Diagnostics GmbH, Penzberg, Germany.

Abstract

Background: D-Dimer testing is a diagnostic tool for exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE). This study evaluated the diagnostic performance of the Tina-quant® D-Dimer Gen.2 assay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) in patients with low/intermediate pre-test probability of DVT/PE using standard, age-, and clinical probability-adjusted cut-offs.

Methods: In this prospective, observational, multicenter study (July 2017-August 2019), plasma samples were collected from hospital emergency departments and specialist referral centers. DVT/PE was diagnosed under hospital standard procedures and imaging protocols. A standard D-dimer cut-off of 0.5 µg fibrinogen equivalent units (FEU)/ml was combined with the three-level Wells score; cut-offs adjusted for age (age × 0.01 µg FEU/ml for patients >50 years) and clinical probability (1 µg FEU/ml for low probability) were also evaluated. An assay comparison was conducted in a subset of samples using the Tina-quant D-Dimer Gen.2 assay and the previously established routine laboratory assay, STA-Liatest D-Di Plus assay (Stago Deutschland GmbH, Düsseldorf, Germany).

Results: 2,897 patients were enrolled; 2,516 completed the study (DVT cohort: 1,741 PE cohort: 775). Clinical assessment plus D-dimer testing using the standard cut-off resulted in 317 (DVT) and 230 (PE) false positives, and zero (DVT) and one (PE) false negatives. Negative predictive value (NPV) was 100.0% (95% confidence interval [CI]: 99.7%-100.0%) and 99.8% (95% CI: 98.8%-100.0%) for DVT and PE, respectively. After age-adjustment, NPV was 99.9% (95% CI: 99.6%-100.0%) and 99.1% (95% CI: 97.8-99.7) for DVT and PE, respectively. False positive rates decreased (>50%) in clinical probability-adjusted analyses vs. primary analysis. In the assay comparison, the performances of the two assays were comparable.

Conclusion: The Tina-quant D-Dimer Gen.2 assay and standard D-dimer cut-off level combined with the three-level Wells score accurately identified patients with a very low probability of DVT/PE.

Keywords: D-Dimer; coagulation assay; cobas t 711; deep vein thrombosis; pulmonary embolism.