Thromb Haemost
DOI: 10.1055/s-0040-1715589
New Technologies, Diagnostic Tools and Drugs

Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study

Debnath Maji*
1  Department of Electrical, Computer, and Systems Engineering, Case Western Reserve University, Cleveland, Ohio, United States
,
Aman Opneja*
2  Hematology and Oncology Division, Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States
3  Division of Hematology-Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
,
Michael A. Suster
1  Department of Electrical, Computer, and Systems Engineering, Case Western Reserve University, Cleveland, Ohio, United States
,
Kara L. Bane
3  Division of Hematology-Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
,
Brigid M. Wilson
4  Geriatric Research Education and Clinical Center, Louis Stokes Cleveland Veterans Administration Medical Center, VA Northeast Ohio Healthcare System, Cleveland, Ohio, United States
5  Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
,
Pedram Mohseni
1  Department of Electrical, Computer, and Systems Engineering, Case Western Reserve University, Cleveland, Ohio, United States
,
3  Division of Hematology-Oncology, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
6  Section of Hematology-Oncology, Department of Medicine, Louis Stokes Cleveland Veterans Administration Medical Center, VA Northeast Ohio Healthcare System, Cleveland, Ohio, United States
› Author Affiliations
Funding 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.

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).

Authors' Contributions

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.


Supplementary Material



Publication History

Received: 03 March 2020

Accepted: 03 July 2020

Publication Date:
02 September 2020 (online)

Georg Thieme Verlag KG
Stuttgart · New York