Microfluidic coagulation assay for monitoring anticoagulant therapy in acute stroke patients

Thromb Haemost. 2017 Feb 28;117(3):519-528. doi: 10.1160/TH16-08-0619. Epub 2017 Jan 26.

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.

Keywords: Stroke; acute; antithrombins; factor Xa antagonists/inhibitors; phenprocoumon; whole blood coagulation time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / blood
  • Automation, Laboratory
  • Blood Coagulation / drug effects*
  • Chromatography, High Pressure Liquid
  • Dabigatran / administration & dosage*
  • Dabigatran / adverse effects
  • Dabigatran / blood
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / drug therapy*
  • Male
  • Microfluidic Analytical Techniques*
  • Microscopy, Fluorescence
  • Middle Aged
  • Phenprocoumon / administration & dosage*
  • Phenprocoumon / adverse effects
  • Phenprocoumon / blood
  • Predictive Value of Tests
  • Pyrazoles / administration & dosage*
  • Pyrazoles / adverse effects
  • Pyrazoles / blood
  • Pyridones / administration & dosage*
  • Pyridones / adverse effects
  • Pyridones / blood
  • Reproducibility of Results
  • Rivaroxaban / administration & dosage*
  • Rivaroxaban / adverse effects
  • Rivaroxaban / blood
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Tandem Mass Spectrometry
  • Time Factors
  • Treatment Outcome
  • Whole Blood Coagulation Time*

Substances

  • Anticoagulants
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran
  • Phenprocoumon