title: Microfluidic coagulation assay for monitoring anticoagulant therapy in acute stroke patients.
abstract: 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 stroke-patients.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Bluecher
authors.forename: Sascha
authors.initials: S
authors.lastname: Meyer Dos Santos
authors.forename: Nerea
authors.initials: N
authors.lastname: Ferreirós
authors.forename: Sandra
authors.initials: S
authors.lastname: Labocha
authors.forename: Isabel Maria Rodrigues
authors.initials: IM
authors.lastname: Meyer Dos Santos
authors.forename: Bettina
authors.initials: B
authors.lastname: Picard-Willems
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
authors.affiliation: Oliver C. Singer, MD, Department of Neurology, HELIOS HSK Kliniken, Ludwig-Erhard-Str. 100, 65199 Wiesbaden, Germany, Tel.: +49 611 432376, Fax: +49 611 432732, E-mail: oliver.c.singer@gmail.com.
authors.forename: Oliver C
authors.initials: OC
authors.lastname: Singer
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D057205:Automation, Laboratory; D001777:Blood Coagulation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D000069604:Dabigatran / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D046210:Microfluidic Analytical Techniques; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010644:Phenprocoumon / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011237:Predictive Value of Tests; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015203:Reproducibility of Results; D000069552:Rivaroxaban / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D016896:Treatment Outcome; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D000069604:Dabigatran; D010644:Phenprocoumon
keywords: Stroke; acute; antithrombins; factor Xa antagonists/inhibitors; phenprocoumon; whole blood coagulation time