Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study

Abstract

Background There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care. Methods We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity (T peak) is a sensitive parameter of coagulation function. We conducted a prospective, single-center, pilot study to determine its clinical utility at detecting DOAC anticoagulant effects in whole blood. Results We accrued 154 individuals: 50 healthy volunteers, 49 rivaroxaban patients, 47 apixaban, and 8 dabigatran patients. Blood samples underwent ClotChip measurements and plasma coagulation tests. Control mean T peak was 428 seconds (95% confidence interval [CI]: 401–455 seconds). For rivaroxaban, mean T peak was 592 seconds (95% CI: 550–634 seconds). A receiver operating characteristic curve showed that the area under the curve (AUC) predicting rivaroxaban using T peak was 0.83 (95% CI: 0.75–0.91, p < 0.01). For apixaban, mean T peak was 594 seconds (95% CI: 548–639 seconds); AUC was 0.82 (95% CI: 0.73–0.91, p < 0.01). For dabigatran, mean T peak was 894 seconds (95% CI: 701–1,086 seconds); AUC was 1 (p < 0.01). Specificity for all DOACs was 88%; sensitivity ranged from 72 to 100%. Conclusion This diagnostic study using samples from “real-world” DOAC patients supports that ClotChip exhibits high sensitivity at detecting DOAC anticoagulant effects in a disposable portable platform, using a miniscule amount of whole blood (<10 µL).

Impact of Integrated Care Management on Clinical Outcomes in Atrial Fibrillation Patients: A Report From the FANTASIIA Registry

“…Good quality anticoagulation (defined as TTR > 70%) is related with better outcomes during follow-up ( 26 – 28 ). In case of DOACs, those drugs have demonstrated similar or higher efficacy in thromboembolic prevention in AF patients with fixed dose and in the absence of drug monitoring ( 29 – 32 ). However, nearly one-third of patients may receive an inappropriate dose of DOAC in daily clinical practice, according to EHRA recommendations ( 33 ), increasing both thromboembolic and bleeding risks ( 34 ).…”

Detection of Direct Oral Anticoagulants in Patient Urine Samples by Prototype and Commercial Test Strips for DOACs – A Systematic Review and Meta-analysis

“…11 Other POCT tests able to determine the presence of DOACs from blood samples have also been reported in the literature. Thromboelastographic methods, 23 global coagulation assays 24 , specific coagulation POCT testing methods using ecarin reagent for determination of dabigatran 25 , a dielectric microsensor after recalcification of a small amount whole blood sample 26 and others. 27 The performance of the urine based DOAC Dipstick to identify DOACs on the studied populations was at least as high as those obtained obtained with specific testing from patients' plasma and whole blood samples using chromogenic assays for DXI or tests based on ecarin reagent for dabigatran measurements.…”

ClotChip Portable Blood Clotting Sensor

“…12,13 In addition, patients who are receiving anticoagulant therapy -such as direct oral anticoagulants (DOACs) -may also benefit from the availability of a PoC device such as ClotChip (i.e., in acute care and emergency surgery settings), as a rapid and accurate assessment of the effects of DOAC therapy on the blood's ability to clot can support safe and effective treatment decisions. 16…”

“…Evidence for ClotChip remains early in its development, mostly limited to pilot and feasibility studies with small sample sizes, ranging from 12 to 104 study participants. 3,16,[21][22][23] Earliest investigations of the technology relied on ex vivo assessments, 3 with later studies using controlled methods and whole blood from study participants. 5 Evidence to date has demonstrated the feasibility of ClotChip in the assessment of coagulation and clinical risk of bleeding, as well as monitoring of coagulation factor replacement therapy, for patients with hemophilia (both with and without inhibitors, as well as for those receiving emicizumab).…”

“…3,23,24 Further investigation has focused on the utility of ClotChip for monitoring DOAC therapy, demonstrating its sensitivity to detect the anticoagulant effects of these drugs. 16 While the accuracy of the ClotChip device has been compared against conventional technologies (including rotational thromboelastometry and thrombin generation assays) and produced comparable results, 19,21,22 no evidence was found that compared ClotChip to another PoC device.…”