Biomedical Microdevices

, 19:64 | Cite as

Point-of-care coagulation monitoring: first clinical experience using a paper-based lateral flow diagnostic device

  • Michael A. Hegener
  • Hua Li
  • Daewoo Han
  • Andrew J. Steckl
  • Giovanni M. Pauletti
Article

Abstract

Vitamin K antagonists such as warfarin are the most widely used class of oral anticoagulants. Due to a narrow therapeutic window, patients on warfarin require regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is available, but cost makes this monitoring method beyond reach for many. The main objective of this research was to assess the clinical utility of a low-cost, paper-based lateral flow POC diagnostic device developed for anticoagulation monitoring without the need for a separate electronic reader. Custom-fabricated lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic backing card were assembled in a plastic cassette. Healthy volunteers and patients on warfarin therapy were recruited for this prospective study. For each participant, a whole blood sample was collected via fingerstick to determine: (1) international normalized ratio (INR) using the CoaguChek® XS coagulometer, (2) hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the experimental LFA device after 240 s using digital image analysis. RBC travel distance measured on the LFA device using blood samples obtained from warfarin patients positively correlated with increasing INR value and the LFA device had the capability to statistically distinguish between healthy volunteer INR values and those for patients groups with INR ≥ 2.6. From these data, it is predicted that this low-cost, paper-based LFA device can have clinical utility for identifying anticoagulated patients taking vitamin K antagonists who are outside of the desired therapeutic efficacy window.

Keywords

Warfarin Coagulation monitoring Lateral flow Paper-based Self-testing Point-of-care 

Notes

Acknowledgements

This research was supported by the National Science Foundation (ENG 1236987) and the University of Cincinnati Research Council Interdisciplinary Program. The authors thank the staff at St. Elizabeth Healthcare (Fort Thomas, KY) for their assistance during the clinical trial.

References

  1. CAP TODAY, Coagulation analyzers—point of care, self-monitoring (College of American Pathologists, Northfield, IL; March (2017), http://www.captodayonline.com/productguides/instruments/coagulation-analyzers-march-2017.html. Accessed April 4, (2017)
  2. CoaguChek XS PT Test [package insert]. Roche Diagnostics, Indianapolis, IN; January. (2016). http://www.coaguchek-usa.com/content/dam/internet/dia/coaguchek/coaguchek-usa_com/coaguchek_hcp/pdf/CoaguChek-XS-Package-Insert-2016.pdf. Accessed April 17, 2017
  3. Coumadin® [package insert]. (Bristol-Myers Squibb Company, Princeton, 2017); May. 2017. https://packageinserts.bms.com/pi/pi_coumadin.pdf. Accessed June 21, 2017
  4. E. Anderson, K. Johnke, D. Leedahl, M. Glogoza, R. Newman, C. Dyke, Am. J. Surg. 210, 1095 (2015)CrossRefGoogle Scholar
  5. J. Ansell, J. Hirsh, E. Hylek, A. Jacobson, M. Crowther, G. Palareti, Chest 133, 160S (2008)CrossRefGoogle Scholar
  6. H.E. Bloomfield, A. Krause, N. Greer, et al., Ann. Intern. Med. 154, 472 (2011)CrossRefGoogle Scholar
  7. L.M. Brass, H.M. Krumholz, J.M. Scinto, M. Radford, Stroke 28, 2382 (1997)CrossRefGoogle Scholar
  8. E. Chiquette, M.G. Amato, H.I. Bussey, Arch. Intern. Med. 158, 1641 (1998)CrossRefGoogle Scholar
  9. Y.I. Cho, J.M. Jung, Int. Commun. Heat. Mass. Transf. 57, 221 (2014)CrossRefGoogle Scholar
  10. J.W. Eikelboom, D.J. Quinlan, J. van Ryn, J.I. Weitz, Circulation 132, 2412 (2015)CrossRefGoogle Scholar
  11. E.W. Errill, Physiol. Rev. 49, 863 (1969)Google Scholar
  12. K.R. Hawkins, B.H. Weigl, Proc. SPIE (2010). doi: 10.1117/12.845500
  13. P.L. Hess, M.J. Mirro, H.-C. Diener, J.W. Eikelboom, S.M. Al-Khatib, E.M. Hylek, H.B. Bosworth, B.J. Gersh, D.E. Singer, G. Flaker, J.L. Mega, E.D. Peterson, J.S. Rumsfeld, B.A. Steinberg, A.K. Kakkar, R.M. Califf, C.B. Granger, Am. Heart J. 168, 239 (2014)CrossRefGoogle Scholar
  14. J.M. Hwang, J. Clemente, K.P. Sharma, T.N. Taylor, C.L. Garwood, J. Manag. Care. Spec. Pharm. 17, 635 (2011)Google Scholar
  15. M. Jones, P. McEwan, C.L. Morgan, J.R. Peters, J. Goodfellow, C.J. Currie, Heart 91, 472 (2005)CrossRefGoogle Scholar
  16. C. Kearon, E.A. Akl, J. Ornelas, A. Blaivas, D. Jimenez, H. Bounameaux, M. Huisman, C.S. King, T.A. Morris, N. Sood, S.M. Stevens, J.R.E. Vintch, P. Wells, S.C. Woller, L. Moores, Chest 149, 315 (2016)CrossRefGoogle Scholar
  17. H. Li, D. Han, M.A. Hegener, G.M. Pauletti, A.J. Steckl, Biomicrofluidics 11, 024116 (2017)CrossRefGoogle Scholar
  18. H. Li, D. Han, G.M. Pauletti, A.J. Steckl, Lab Chip 14, 4035 (2014)CrossRefGoogle Scholar
  19. R. Lozano, M. Naghavi, K. Foreman, S. Lim, K. Shibuya, V. Aboyans, J. Abraham, T. Adair, R. Aggarwal, S.Y. Ahn, M.A. AlMazroa, M. Alvarado, H.R. Anderson, L.M. Anderson, K.G. Andrews, C. Atkinson, L.M. Baddour, S. Barker-Collo, D.H. Bartels, M.L. Bell, E.J. Benjamin, D. Bennett, K. Bhalla, B. Bikbov, A.B. Abdulhak, G. Birbeck, F. Blyth, I. Bolliger, S. Boufous, C. Bucello, M. Burch, P. Burney, J. Carapetis, H. Chen, D. Chou, S.S. Chugh, L.E. Coffeng, S.D. Colan, S. Colquhoun, K.E. Colson, J. Condon, M.D. Connor, L.T. Cooper, M. Corriere, M. Cortinovis, K.C. de Vaccaro, W. Couser, B.C. Cowie, M.H. Criqui, M. Cross, K.C. Dabhadkar, N. Dahodwala, D. De Leo, L. Degenhardt, A. Delossantos, J. Denenberg, D.C. Des Jarlais, S.D. Dharmaratne, E.R. Dorsey, T. Driscoll, H. Duber, B. Ebel, P.J. Erwin, P. Espindola, M. Ezzati, V. Feigin, A.D. Flaxman, M.H. Forouzanfar, F.G.R. Fowkes, R. Franklin, M. Fransen, M.K. Freeman, S.E. Gabriel, E. Gakidou, F. Gaspari, R.F. Gillum, D. Gonzalez-Medina, Y.A. Halasa, D. Haring, J.E. Harrison, R. Havmoeller, R.J. Hay, B. Hoen, P.J. Hotez, D. Hoy, K.H. Jacobsen, S.L. James, R. Jasrasaria, S. Jayaraman, N. Johns, G. Karthikeyan, N. Kassebaum, A. Keren, J.-P. Khoo, L.M. Knowlton, O. Kobusingye, A. Koranteng, R. Krishnamurthi, M. Lipnick, S.E. Lipshultz, S.L. Ohno, J. Mabweijano, M.F. MacIntyre, L. Mallinger, L. March, G.B. Marks, R. Marks, A. Matsumori, R. Matzopoulos, B.M. Mayosi, J.H. McAnulty, M.M. McDermott, J. McGrath, Z.A. Memish, G.A. Mensah, T.R. Merriman, C. Michaud, M. Miller, T.R. Miller, C. Mock, A.O. Mocumbi, A.A. Mokdad, A. Moran, K. Mulholland, M.N. Nair, L. Naldi, K.M.V. Narayan, K. Nasseri, P. Norman, M. O'Donnell, S.B. Omer, K. Ortblad, R. Osborne, D. Ozgediz, B. Pahari, J.D. Pandian, A.P. Rivero, R.P. Padilla, F. Perez-Ruiz, N. Perico, D. Phillips, K. Pierce, C.A. Pope, E. Porrini, F. Pourmalek, M. Raju, D. Ranganathan, J.T. Rehm, D.B. Rein, G. Remuzzi, F.P. Rivara, T. Roberts, F.R. De León, L.C. Rosenfeld, L. Rushton, R.L. Sacco, J.A. Salomon, U. Sampson, E. Sanman, D.C. Schwebel, M. Segui-Gomez, D.S. Shepard, D. Singh, J. Singleton, K. Sliwa, E. Smith, A. Steer, J.A. Taylor, B. Thomas, I.M. Tleyjeh, J.A. Towbin, T. Truelsen, E.A. Undurraga, N. Venketasubramanian, L. Vijayakumar, T. Vos, G.R. Wagner, M. Wang, W. Wang, K. Watt, M.A. Weinstock, R. Weintraub, J.D. Wilkinson, A.D. Woolf, S. Wulf, P.-H. Yeh, P. Yip, A. Zabetian, Z.-J. Zheng, A.D. Lopez, C.J.L. Murray, Lancet 380, 2095 (2012)CrossRefGoogle Scholar
  20. E.S. Mearns, C.G. Kohn, J.-S. Song, J. Hawthorne, J. Meng, C.M. White, M.K. Raut, J.R. Schein, C.I. Coleman, Thromb. Res. 134, 310 (2014)CrossRefGoogle Scholar
  21. S.I. O’Shea, M.O. Arcasoy, G. Samsa, S.E. Cummings, E.H. Thames, R.S. Surwit, T.L. Ortel, J. Thromb. Thrombolysis 26, 14 (2008)CrossRefGoogle Scholar
  22. I.M. Ogilvie, N. Newton, S.A. Welner, W. Cowell, G.Y.H. Lip, Am. J. Med. 123, 638 (2010)CrossRefGoogle Scholar
  23. P.T. Onundarson, C.W. Francis, O.S. Indridason, D.O. Arnar, E.S. Bjornsson, M.K. Magnusson, S.J. Juliusson, H.M. Jensdottir, B. Vidarsson, P.S. Gunnarsson, S.H. Lund, B.R. Gudmundsdottir, Lancet Haematol. 2, e231 (2015)CrossRefGoogle Scholar
  24. C.S. Phibbs, S.R. Love, A.K. Jacobson, R. Edson, P. Su, L. Uyeda, D.B. Matchar, J. Gen. Intern. Med. 31, 1061 (2016)CrossRefGoogle Scholar
  25. D. Pugh, J. Pugh, G.E. Mead, Age Ageing 40, 675 (2011)CrossRefGoogle Scholar
  26. M. Ranucci, T. Laddomada, M. Ranucci, E. Baryshnikova, Physiol. Rep. 2, e12065 (2014)CrossRefGoogle Scholar
  27. E.K. Rideal, Philos. Mag. 44, 1152 (1922)CrossRefGoogle Scholar
  28. C.A. Schneider, W.S. Rasband, K.W. Eliceiri, Nat. Methods 9, 671 (2012)CrossRefGoogle Scholar
  29. J.B. Segur, H.E. Oberstar, Ind. Eng. Chem. 43, 2117 (1951)CrossRefGoogle Scholar
  30. B.S. Stambler, L.M. Ngunga, Int. J. Gen. Med. 8, 231 (2015)CrossRefGoogle Scholar
  31. E.W. Washburn, Phys. Rev. 17, 273 (1921)CrossRefGoogle Scholar
  32. M. Wieloch, A. Själander, V. Frykman, M. Rosenqvist, N. Eriksson, P.J. Svensson, Eur. Heart J. 32, 2282 (2011)CrossRefGoogle Scholar
  33. J.J. You, D.E. Singer, P.A. Howard, D.A. Lane, M.H. Eckman, M.C. Fang, E.M. Hylek, S. Schulman, A.S. Go, M. Hughes, F.A. Spencer, W.J. Manning, J.L. Halperin, G.Y.H. Lip, Chest 141, e531S (2012)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.James L. Winkle College of PharmacyUniversity of CincinnatiCincinnatiUSA
  2. 2.Nanoelectronics Laboratory, Department of Electrical Engineering and Computer ScienceUniversity of CincinnatiCincinnatiUSA

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