Specific Point-of-Care Testing of Coagulation in Patients Treated with Dabigatran

Florian Härtig; Ingvild Birschmann; Andreas Peter; Matthias Ebner; Charlotte Spencer; Michael Gramlich; Hardy Richter; Joachim Kuhn; Rainer Lehmann; Gunnar Blumenstock; Christine S. Zuern; Ulf Ziemann; Sven Poli

doi:10.1055/s-0040-1721775

Thrombosis and Haemostasis, Table of Contents

CC BY-NC-ND 4.0 · Thromb Haemost 2021; 121(06): 782-791
DOI: 10.1055/s-0040-1721775

New Technologies, Diagnostic Tools and Drugs

Specific Point-of-Care Testing of Coagulation in Patients Treated with Dabigatran

Florian Härtig

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

,

Ingvild Birschmann

³Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Ruhr University, Bad Oeynhausen, Germany

,

Andreas Peter

⁴German Centre for Diabetes Research (DZD), Neuherberg, Germany

⁵Institute for Diabetes Research and Metabolic Diseases, Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany

⁶Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, Tübingen, Germany

,

Matthias Ebner

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

⁷Department of Internal Medicine and Cardiology, Campus Virchow Hospital, Charité, Berlin, Germany

,

Charlotte Spencer

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

,

Michael Gramlich

⁸Department of Cardiology, University Hospital Tübingen, Germany

,

Hardy Richter

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

,

Joachim Kuhn

³Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center, Ruhr University, Bad Oeynhausen, Germany

,

Rainer Lehmann

⁴German Centre for Diabetes Research (DZD), Neuherberg, Germany

⁵Institute for Diabetes Research and Metabolic Diseases, Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany

⁶Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, Tübingen, Germany

,

Gunnar Blumenstock

⁹Department of Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany

,

Christine S. Zuern

⁸Department of Cardiology, University Hospital Tübingen, Germany

¹⁰Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Basel, Switzerland

,

Ulf Ziemann

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

,

Sven Poli

¹Department of Neurology & Stroke, Eberhard Karls University of Tübingen, Tübingen, Germany

²Hertie Institute for Clinical Brain Research, Eberhard Karls University of Tübingen, Tübingen, Germany

› Author Affiliations

Abstract

Background and Purpose Accurate and rapid assessment of coagulation status is necessary to guide thrombolysis or reversal of anticoagulation in stroke patients, but commercially available point-of-care (POC) assays are not suited for coagulation testing in patients treated with direct oral anticoagulants (DOACs). We aimed to evaluate the direct thrombin monitoring (DTM) test card by Helena Laboratories (Texas, United States) for anti-IIa-specific POC coagulation testing, hypothesizing that its POC-ecarin clotting time (POC-ECT) accurately reflects dabigatran plasma concentrations.

Methods A prospective single-center diagnostic study (ClinicalTrials.gov-identifier: NCT02825394) was conducted enrolling patients receiving a first dose of dabigatran and patients already on dabigatran treatment. Blood samples were collected before drug intake and 0.5, 1, 2, 8, and 12 hours after intake. POC-ECT was performed using whole blood (WB), citrated blood (CB), and citrated plasma (CP). Dabigatran plasma concentrations were determined by mass spectrometry.

Results In total, 240 blood samples from 40 patients contained 0 to 275 ng/mL of dabigatran. POC-ECT with WB/CB/CP ranged from 20 to 186/184/316 seconds. Pearson's correlation coefficient showed a strong correlation between dabigatran concentrations and POC-ECT with WB/CB/CP (R² = 0.78/0.90/0.92). Dabigatran concentrations >30 and >50 ng/mL (thresholds for thrombolysis, surgery, and reversal therapy according to clinical guidelines) were detected by POC-ECT with WB/CB/CP (>36/35/45 and >43/45/59 seconds) with 95/97/97 and 96/98/97% sensitivity, and 81/87/94 and 74/60/91% specificity.

Conclusion This first study evaluating DOAC-specific POC coagulation testing revealed an excellent correlation of POC-ECT with actual dabigatran concentrations. Detecting clinically relevant dabigatran levels with high sensitivity/specificity, the DTM assay represents a suitable diagnostic tool in acute stroke, hemorrhage, and urgent surgery.

Keywords

dabigatran - point-of-care testing - ecarin clotting time - thrombolysis - anticoagulation

Full Text

References

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Supplementary Material

Supplementary Material