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Clinical Chemistry 44: 606-613, 1998;
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(Clinical Chemistry. 1998;44:606-613.)
© 1998 American Association for Clinical Chemistry, Inc.

Automation and Analytical Techniques

Improved protamine-sensitive membrane electrode for monitoring heparin concentrations in whole blood via protamine titration§

Narayanan Ramamurthy1, Narayan Baliga2, Joyce A. Wahr2, Ulrich Schaller1, Victor C. Yang3, and Mark E. Meyerhoff1,a

1 Departments of Chemistry and
2 Anesthesiology, and
3 College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109.
a Address correspondence to this author at: Department of Chemistry, The University of Michigan, 930 N. University Ave., Ann Arbor, MI 48109-1055. Fax 313-647-4865; e-mail mmeyerho{at}umich.edu.

An improved protamine-sensitive electrode based on a polymeric membrane doped with the charged ion exchanger dinonylnaphthalenesulfonate (DNNS) is used for monitoring heparin concentrations in whole blood. The electrode exhibits significant nonequilibrium potentiometric response to polycationic protamine over the concentration range of 0.5–20 mg/L in undiluted whole-blood samples. The sensor can serve as a simple end point detector for the determination of heparin via potentiometric titrations with protamine. Whole-blood heparin concentrations determined by the electrode method (n >=157) correlate well with other protamine titration-based methods, including the commercial Hepcon HMS assay (r = 0.934) and a previously reported potentiometric heparin sensor-based method (r = 0.973). Reasonable correlation was also found with a commercial chromogenic anti-Xa heparin assay (r = 0.891) with corresponding plasma samples and appropriate correction for whole-blood hematocrit levels. Whereas a significant positive bias (0.62 kU/L; P <0.001) is observed between the anti-Xa assay and the protamine sensor methods, insignificant bias is observed between the protamine sensor and the Hepcon HMS tests (0.08 kU/L; P = 0.02). The possibility of fully automating these titrations offers a potentially simple, inexpensive, and accurate method for monitoring heparin concentrations in whole blood.




The following articles in journals at HighWire Press have cited this article:


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 Proc. Natl. Acad. Sci. USAHome page
N. M. Milovic, J. R. Behr, M. Godin, C.-S. J. Hou, K. R. Payer, A. Chandrasekaran, P. R. Russo, R. Sasisekharan, and S. R. Manalis
Monitoring of heparin and its low-molecular-weight analogs by silicon field effect
PNAS, September 5, 2006; 103(36): 13374 - 13379.
[Abstract] [Full Text] [PDF]


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