A novel μ-fluidic whole blood coagulation assay based on Rayleigh surface-acoustic waves as a point-of-care method to detect anticoagulants

SummaryReliable 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.

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A Quick Anti-Xa-Activity-Based Whole Blood Coagulation Assay for Monitoring Unfractionated Heparin During Cardiopulmonary Bypass: A Pilot Investigation

Anesthesia & Analgesia ◽

10.1097/00000539-200009000-00006 ◽

2000 ◽

pp. 533-538 ◽

Cited By ~ 1

Author(s):

Roland Hansen ◽

Andreas Koster ◽

Marian Kukucka ◽

Fritz Mertzlufft ◽

Herrmann Kuppe

Keyword(s):

Cardiopulmonary Bypass ◽

Unfractionated Heparin ◽

Blood Coagulation ◽

Whole Blood ◽

Pilot Investigation ◽

Coagulation Assay

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Point-of-care testing and INR within-subject variation in patients receiving a constant dose of vitamin K antagonist

Thrombosis and Haemostasis ◽

10.1160/th15-02-0128 ◽

2015 ◽

Vol 114 (12) ◽

pp. 1260-1267

Author(s):

Joseph S. Biedermann ◽

Marieke J. H. A. Kruip ◽

A. M. H. P. van den Besselaar

Keyword(s):

Blood Coagulation ◽

Vitamin K ◽

Whole Blood ◽

Point Of Care ◽

Vitamin K Antagonists ◽

Professional Staff ◽

Self Testing ◽

Target Intensity ◽

Constant Dose ◽

Coaguchek Xs

SummaryMany patients treated with vitamin K antagonists (VKA) determine their INR using point-of-care (POC) whole blood coagulation monitors. The primary aim of the present study was to assess the INR within-subject variation in self-testing patients receiving a constant dose of VKA. The second aim of the study was to derive INR imprecision goals for whole blood coagulation monitors. Analytical performance goals for INR measurement can be derived from the average biological within-subject variation. Fifty-six Thrombosis Centres in the Netherlands were invited to select self-testing patients who were receiving a constant dose of either acenocoumarol or phenprocoumon for at least six consecutive INR measurements. In each patient, the coefficient of variation (CV) of INRs was calculated. One Thrombosis Centre selected regular patients being monitored with a POC device by professional staff. Sixteen Dutch Thrombosis Centres provided results for 322 selected patients, all using the CoaguChek XS. The median within-subject CV in patients receiving acenocoumarol (10.2 %) was significantly higher than the median CV in patients receiving phenprocoumon (8.6 %) (p = 0.001). The median CV in low-target intensity acenocoumarol self-testing patients (10.4 %) was similar to the median CV in regular patients monitored by professional staff (10.2 %). Desirable INR analytical imprecision goals for POC monitoring with CoaguChek XS in patients receiving either low-target intensity acenocoumarol or phenprocoumon were 5.1 % and 4.3 %, respectively. The approximate average value for the imprecision of the CoaguChek XS, i. e. 4 %, is in agreement with these goals.

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A Quick Anti-Xa-Activity-Based Whole Blood Coagulation Assay for Monitoring Unfractionated Heparin During Cardiopulmonary Bypass: A Pilot Investigation

Anesthesia & Analgesia ◽

10.1213/00000539-200009000-00006 ◽

2000 ◽

Vol 91 (3) ◽

pp. 533-538 ◽

Cited By ~ 8

Author(s):

Roland Hansen ◽

Andreas Koster ◽

Marian Kukucka ◽

Fritz Mertzlufft ◽

Herrmann Kuppe

Keyword(s):

Cardiopulmonary Bypass ◽

Unfractionated Heparin ◽

Blood Coagulation ◽

Whole Blood ◽

Pilot Investigation ◽

Coagulation Assay

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Comprehensive Blood Coagulation Profiling in Patients Using iCoagLab: Comparison Against Thromboelastography

Thrombosis and Haemostasis ◽

10.1055/s-0040-1712956 ◽

2020 ◽

Vol 120 (07) ◽

pp. 1116-1127 ◽

Cited By ~ 1

Author(s):

Markandey M. Tripathi ◽

Diane M. Tshikudi ◽

Zeinab Hajjarian ◽

Dallas C. Hack ◽

Elizabeth M. Van Cott ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Blood Coagulation ◽

Whole Blood ◽

Point Of Care ◽

Bleeding Risk ◽

Laser Speckle ◽

Progression Rate ◽

Accurate Identification ◽

Blood Samples ◽

Speckle Patterns

AbstractDelayed identification of coagulopathy and bleeding increases the risk of organ failure and death in hospitalized patients. Timely and accurate identification of impaired coagulation at the point-of-care can proactively identify bleeding risk and guide resuscitation, resulting in improved outcomes for patients. We test the accuracy of a novel optical coagulation sensing approach, termed iCoagLab, for comprehensive whole blood coagulation profiling and investigate its diagnostic accuracy in identifying patients at elevated bleeding risk. Whole blood samples from patients (N = 270) undergoing conventional coagulation testing were measured using the iCoagLab device. Recalcified and kaolin-activated blood samples were loaded in disposable cartridges and time-varying intensity fluctuation of laser speckle patterns were measured to quantify the clot viscoelastic modulus during coagulation. Coagulation parameters including the reaction time (R), clot progression time (K), clot progression rate (α), and maximum clot strength (MA) were derived from clot viscoelasticity traces and compared with mechanical thromboelastography (TEG). In all patients, a good correlation between iCoagLab- and TEG-derived parameters was observed (p < 0.001). Multivariate analysis showed that iCoagLab-derived parameters identified bleeding risk with sensitivity (94%) identical to, and diagnostic accuracy (89%) higher than TEG (87%). The diagnostic specificity of iCoagLab (77%) was significantly higher than TEG (69%). By rapidly and comprehensively permitting blood coagulation profiling the iCoagLab innovation is likely to advance the capability to identify patients with elevated risk for bleeding, with the ultimate goal of preventing life-threatening hemorrhage.

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

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1676318 ◽

2018 ◽

Vol 45 (03) ◽

pp. 253-258 ◽

Cited By ~ 1

Author(s):

Sebastian Harder ◽

Sascha Santos ◽

Viktor Krozer ◽

Jochen Moll

Keyword(s):

Acoustic Waves ◽

Point Of Care ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Surface Acoustic Waves ◽

Dependent Manner ◽

Coagulation Test ◽

Novel Device ◽

Point Of Care Test ◽

Small Patient Population

AbstractAn universal coagulation test that reliably detects prolonged coagulation times in patients, regardless of which anticoagulant is administered, is not yet available. The authors developed a novel, miniaturized device utilizing surface acoustic waves (SAW) to detect clotting, and used it to develop a novel universal microfluidic coagulation test. Results from this assay were compared with results from standard coagulation assays to detect classical anticoagulants (unfractionated heparin, argatroban) and direct oral anticoagulants (dabigatran, rivaroxaban). The SAW-clotting time (SAW-CT) of this novel device was prolonged in a dose-dependent manner for heparin, argatroban, dabigatran, and rivaroxaban, comparable to standard assays. The authors confirmed the clinical utility of this device in a small patient population admitted to a stroke unit. Preliminary clinical data prove the suitability of the SAW-CT in patients receiving warfarin, rivaroxaban, or dabigatran. The device could be particularly useful as a point-of-care test to assess whole blood coagulation (e.g., in stroke units or in other emergency settings).

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An Urinary Biosensor for Early Stage Ovarian Cancer Detection: Experimental Characterization

Volume 9: Micro- and Nano-Systems Engineering and Packaging, Parts A and B ◽

10.1115/imece2012-87850 ◽

2012 ◽

Author(s):

Onursal Onen ◽

Alper Sisman ◽

Patricia Kruk ◽

Rasim O. Guldiken

Keyword(s):

Ovarian Cancer ◽

Acoustic Waves ◽

Early Stage ◽

Point Of Care ◽

Surface Acoustic Waves ◽

Experimental Characterization ◽

Apoptotic Protein ◽

Polarized Surface ◽

Shear Horizontal

In this study, an experimental characterization of a piezoelectric ultrasonic MEMS biosensor for detection of anti-apoptotic protein Bcl-2 in sub ng/ml scale is presented. Bcl-2 is demonstrated to be elevated at different stages of ovarian cancer in urine ranging from 0.5 to 12 ng/ml. Here, shear horizontal (SH) polarized surface acoustic waves (SAWs) were utilized by interdigital transducers (IDTs), which were micro fabricated on piezoelectric ST cut Quartz wafers. SH SAWs were generated and sensed by a pair of IDTs, separated by judiciously designed a delay path in-between with for most effective Bcl-2 capture. The Bcl-2 concentration is characterized with respect to the change in resonance frequency. The target sensitivity for diagnosis and quantifying the stage of ovarian cancer is achieved with successful detection of Bcl-2 levels as low as 0.5 ng/ml. The results are promising for the sensor system to be used in a lab-on-a-chip platform for point of care urinary ovarian cancer monitoring diagnosis.

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