Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical StudyFunding This work was supported by an American Heart Association Grant-in-Aid award (17GRNT33661005 to M.A.S., P.M., and E.X.S.), by XaTek, Inc. and the Oscar D. Ratnoff Endowed Professorship (to E.X.S.). The contents do not represent the views of the US Department of Veterans Affairs or the United States Government.
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).
Keywordsanticoagulation - monitoring - direct oral anticoagulants - point of care - coagulation tests
D.M., M.A.S., A.O., P.M., and E.X.S. conceptualized and designed the research; A.O. and E.X.S. designed the clinical study. D.M., M.A.S., K.L.B., and E.X.S. performed the research. D.M., A.O., M.A.S., K.L.B., B.M.W., P.M., and E.X.S. analyzed the data. B.M.W. provided analytical tools. D.M., A.O., M.A.S., P.M., and E.X.S. prepared the figures. A.O. and E.X.S. wrote the manuscript. All authors reviewed the manuscript before submission.
* Drs. Maji and Opneja contributed equally to this article.
Received: 03 March 2020
Accepted: 03 July 2020
02 September 2020 (online)
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