Microfluidic coagulation assay for monitoring anticoagulant therapy in acute stroke patients

Annemarie Bluecher; Sascha Meyer dos Santos; Nerea Ferreirós; Sandra Labocha; Isabel Maria Rodrigues Meyer dos Santos; Bettina Picard-Willems; Sebastian Harder; Oliver C. Singer

doi:10.1160/TH16-08-0619

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2017; 117(03): 519-528
DOI: 10.1160/TH16-08-0619

Coagulation and Fibrinolysis

Schattauer GmbH

Microfluidic coagulation assay for monitoring anticoagulant therapy in acute stroke patients

Annemarie Bluecher

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

,

Sascha Meyer dos Santos

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

²Fraunhofer Institute IME, Project Group Translational Medicine and Pharmacology, Frankfurt am Main, Germany

,

Nerea Ferreirós

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

,

Sandra Labocha

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

,

Isabel Maria Rodrigues Meyer dos Santos

³Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany

,

Bettina Picard-Willems

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

,

Sebastian Harder

¹Clinical Pharmacology, Goethe University Hospital, Frankfurt am Main, Germany

,

Oliver C. Singer

³Department of Neurology, Goethe University Hospital, Frankfurt am Main, Germany

⁴HELIOS Dr. Horst Schmidt Kliniken, Department of Neurology, Wiesbaden, Germany

› Author Affiliations

Abstract

Summary

Reliable detection of anticoagulation status in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs) is challenging but of importance especially in the emergency setting. This study evaluated the potential of a whole-blood clotting time assay based on Surface Acoustic Waves (SAW-CT) in stroke-patients. The SAW-technology was used for quick and homogenous recalcification of whole blood inducing a surface-activated clotting reaction quantified and visualised by real-time fluorescence microscopy with automatic imaging processing. In 20 stroke or transient ischaemic attack (TIA)-patients taking NOACs kinetics of SAW-CT were assessed and correlated to other coagulation parameters (PT, aPTT) and NOAC-plasma concentration measured by tandem mass spectrometry (LC-MS/MS). In 225 emergency patients with suspicion of acute stroke or TIA, SAW-CT values were assessed. Mean (± SD) SAW-CT in non-anticoagulated stroke patients (n=180) was 124 s (± 21). In patients on dabigatran or rivaroxaban, SAW-CT values were significantly higher 2 and 8 hours (h) after intake rising up to 267 seconds (s) (dabigatran, 2 h after intake) and 250 s (rivaroxaban, 8 h after intake). In patients on apixaban, SAW-CT values were only moderately increased 2 h after intake (SAW-CT 153 s). In emergency patients, SAW-CT values were significantly higher in NOAC and vitamin K antagonist (VKA)-treated as compared to non-anticoagulated patients. In conclusion, the SAW-CT assay is capable to monitor anticoagulant level and effect in patients receiving dabigatran, rivaroxaban and the VKA phenprocoumon. It has a limited sensitivity for apixaban-detection. If specific SAW-CT results were used as cut-offs, SAW-CT yields high diagnostic accuracy to exclude relevant rivaroxaban and dabigatran concentrations in strokepatients.

Keywords

Stroke - acute - factor Xa antagonists/inhibitors - antithrombins - phen-procoumon - whole blood coagulation time

Full Text

References

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