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.

Accuracy of a Rapid Diagnostic Test for the Presence of Direct Oral Factor Xa or Thrombin Inhibitors in Urine—A Multicenter Trial

“…The intention-to-analyze evaluation confirmed the results of the per-protocol evaluation (►Tables [6][7][8]. There were no differences of these results with those of the per-protocol evaluation.…”

“…[3][4][5] Various tests are in different stages of development. [6][7][8] Emergency situations with a need for point-of-care testing for the presence or absence of DOACs include emergent or urgent major surgical interventions, clinically relevant bleeding, or thrombotic episodes with known or unknown anticoagulant therapy, as well as the evaluation of unconscious patients or those unable to inform clinicians about their anticoagulant therapy. 9,10 Knowledge of the presence of a DOAC may inform use of expensive reversal agents, which would not be indicated in a patient without detectable DOAC exposure.…”

Detecting Anti-IIa and Anti-Xa Direct Oral Anticoagulant (DOAC) Agents in Urine using a DOAC Dipstick

“…This assay can determine the anticoagulant level in patients receiving dabigatran, rivaroxaban, and phenprocoumon, but not apixaban. 17 The Hemochron Signature system (Accriva Diagnostics) uses testing cards that measure the activated clotting time (ACT) and PT and determines blood coagulation by photo-detection. The ACT and PT are prolonged in the presence of vitamin K antagonists (VKAs), DOACs, and heparins if reagents do not contain heparin neutralizers.…”

Surface Acoustic Wave-Based Microfluidic Coagulation Device for Monitoring Anticoagulant Therapy

“…When SAW-CT results in non-anticoagulated patients were used to determine a SAW-CT cutoff, SAW-CT was able to exclude relevant rivaroxaban concentrations in stroke patients. 7 A concentration of 100 ng/mL rivaroxaban has been suggested as possible cutoff level for safe thrombolysis in stroke patients, according to a consensus study. 9 A prototype has been developed with similar performance characteristics 6 (►Fig.…”

“…In 225 emergency patients (123 males, 102 females) with suspicion of an acute cerebrovascular event, SAW-CT values were assessed. 7 Mean age of this cohort was 73 AE 13 years, and final diagnoses (after clinical investigation and imaging procedures) were ischemic stroke (n ¼ 154), transitory ischemic attack (TIA; n ¼ 29), intracerebral hemorrhage (n ¼ 14), epileptic seizure (n ¼ 14), and other nonneurological diagnoses (n ¼ 14). For comparison, liquid chromatography-mass spectrometry (LC-MS)/MS was used to determine dabigatran, rivaroxaban, and apixaban plasma levels.…”