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Effect of Fibrinogen on Platelet Reactivity Measured by the VerifyNow P2Y12 Assay

A. B. Dobrovolsky1*, P. S. Laguta1, E. V. Guskova1, E. B. Yarovaya2, E. V. Titaeva1, A. N. Storozhilova1, and E. P. Panchenko1

1Russian Cardiology Research and Production Complex, Ministry of Healthcare, 121552 Moscow, Russia; fax: +7 (495) 414-6699; E-mail: abdobrovolsky@inbox.ru

2Lomonosov Moscow State University, Faculty of Mechanics and Mathematics, 119899 Moscow, Russia

* To whom correspondence should be addressed.

Received January 15, 2016; Revision received February 12, 2016
The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = −63.3 × dFg − 27.1 (r = −0.924, p < 0.0005) and dPRU = −54.4 × dFg − 21.8 (r = −0.764, p < 0.0005). Thus, the results of our experiments suggest that: (i) blood fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy.
KEY WORDS: platelets, fibrinogen, P2Y12 inhibitors, VerifyNow test

DOI: 10.1134/S0006297916050011