Platelet and coagulation hemostasis status in patients with atrial fibrillation depending on warfarin dosing method




atrial fibrillation, warfarin, platelet aggregation, D-dimer, genotype-guided dosing


The aim. To evaluate indicators of induced platelet aggregation and D-dimer level in patients with atrial fibrillation (AF) depending on the method of warfarin (WF) dosing.

Materials and methods. The study involved 110 patients with AF (mean age 68.72 ± 0.79; men – 57, women – 53). Patients with AF were divided into two groups: the main group – 50 patients with AF and genotype-guided dosing method, the control group – 60 patients with AF and traditional dosing method. CYP2C9, CYP4F2, VKORC1 genetic polymorphisms were determined using multiplex real time polymerase chain reaction, D-dimer concentration – by the method of solid-phase enzyme immunoassay; ADP- and epinephrine-induced aggregation indicators – by the method of G. Born.

Results. The percentage (by 24 %), time (by 3 min 6 s) and rate in 30 s (by 19.5 %/min) of ADP-induced platelet aggregation were significantly lower in patients with AF and genotype-guided WF dosing method. D-dimer concentration in patients of the main and control groups did not differ significantly. However, significantly fewer patients with elevated D-dimer values were registered in the group with genotype-guided WF dosing method compared to the group with traditional dosing method: 0 (0.00 %) vs. 7 (11.67 %) at 500 ng FEU/ml cut-off (χ2 = 4.43, P < 0.05), 1 (2.00 %) vs. 9 (15.00 %) at 390 ng FEU/ml cut-off (χ2 = 4.16, P < 0.05), 0 (0.00 %) vs. 7 (11.67 %) at age-adjusted cut-off (χ2 = 4.43, P < 0.05).

Conclusions. The obtained results may indicate a potentially lower risk of thrombotic events in patients with AF and genotype-guided WF dosing method compared to the group with traditional dosing method, which confirms the benefit of the widespread use of the pharmacogenetic testing in clinical practice.

Author Biographies

M. Yu. Kolesnyk, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Family Medicine, Therapy, Cardiology and Neurology of the Faculty of Postgraduate Education

Ya. M. Mykhailovskyi, Zaporizhzhia State Medical University, Ukraine

PhD-student of the Department of Family Medicine, Therapy, Cardiology and Neurology of Faculty of Postgraduate Education


Ding, W. Y., Gupta, D., & Lip, G. (2020). Atrial fibrillation and the prothrombotic state: revisiting Virchow's triad in 2020. Heart (British Cardiac Society), 106(19), 1463-1468.

Kosiuk, J., Uhe, T., Stegmann, C., Ueberham, L., Bertagnolli, L., Dagres, N., Dinov, B., Müssigbrodt, A., Richter, S., Paetsch, I., Jahnke, C., Hilbert, S., Sommer, P., Hindricks, G., & Bollmann, A. (2019). Morphological determinators of platelet activation status in patients with atrial fibrillation. International journal of cardiology, 279, 90-95.

Willoughby, S. R., Roberts-Thomson, R. L., Lim, H. S., Schultz, C., Prabhu, A., De Sciscio, P., Wong, C. X., Worthley, M. I., & Sanders, P. (2010). Atrial platelet reactivity in patients with atrial fibrillation. Heart rhythm, 7(9), 1178-1183.

Gosk-Bierska, I., Wasilewska, M., & Wysokiński, W. (2016). Role of Platelets in Thromboembolism in Patients with Atrial Fibrillation. Advances in clinical and experimental medicine, 25(1), 163-171.

Procter, N. E., Ball, J., Ngo, D. T., Chirkov, Y. Y., Isenberg, J. S., Hylek, E. M., Stewart, S., & Horowitz, J. D. (2016). Platelet hyperaggregability in patients with atrial fibrillation. Evidence of a background proinflammatory milieu. Herz, 41(1), 57-62.

Choi, J. H., Cha, J. K., & Huh, J. T. (2014). Adenosine diphosphate-induced platelet aggregation might contribute to poor outcomes in atrial fibrillation-related ischemic stroke. Journal of stroke and cerebrovascular, 23(3), e215-e220.

Weitz, J. I., Fredenburgh, J. C., & Eikelboom, J. W. (2017). A Test in Context: D-Dimer. Journal of the American College of Cardiology, 70(19), 2411-2420.

Siegbahn, A., Oldgren, J., Andersson, U., Ezekowitz, M. D., Reilly, P. A., Connolly, S. J., Yusuf, S., Wallentin, L., & Eikelboom, J. W. (2016). D-dimer and factor VIIa in atrial fibrillation - prognostic values for cardiovascular events and effects of anticoagulation therapy. A RE-LY substudy. Thrombosis and haemostasis, 115(5), 921-930.

Christersson, C., Wallentin, L., Andersson, U., Alexander, J. H., Ansell, J., De Caterina, R., Gersh, B. J., Granger, C. B., Hanna, M., Horowitz, J. D., Huber, K., Husted, S., Hylek, E. M., Lopes, R. D., & Siegbahn, A. (2014). D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation--observations from the ARISTOTLE trial. Journal of thrombosis and haemostasis : JTH, 12(9), 1401-1412.

Ruff, C. T., Giugliano, R. P., Braunwald, E., Murphy, S. A., Brown, K., Jarolim, P., Mercuri, M., Antman, E. M., & Morrow, D. A. (2016). Cardiovascular Biomarker Score and Clinical Outcomes in Patients with Atrial Fibrillation: A Subanalysis of the ENGAGE AF-TIMI 48 Randomized Clinical Trial. JAMA cardiology, 1(9), 999-1006.

Douma, R. A., le Gal, G., Söhne, M., Righini, M., Kamphuisen, P. W., Perrier, A., Kruip, M. J., Bounameaux, H., Büller, H. R., & Roy, P. M. (2010). Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ (Clinical research ed.), 340, c1475.

Almorad, A., Ohanyan, A., Pintea Bentea, G., Wielandts, J. Y., El Haddad, M., Lycke, M., O'Neill, L., Morissens, M., De Keyzer, E., Nguyen, T., Anghel, L., Samyn, S., Berdaoui, B., Tavernier, R., Vandekerckhove, Y., Duytschaever, M., Verbeet, T., Knecht, S., & Castro Rodriguez, J. (2021). D-dimer blood concentrations to exclude left atrial thrombus in patients with atrial fibrillation. Heart (British Cardiac Society), 107(3), 195-200.

Du, X., & Wang, Y. (2019). The diagnostic efficacy of cardiac CTA combined with D-dimer assay for the detection of left atrial thrombus in patients with atrial fibrillation. The American journal of emergency medicine, 37(10), 1922-1926.

Diaz-Arocutipa, C., Gonzales-Luna, A. C., Brañez-Condorena, A., & Hernandez, A. V. (2021). Diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation: A systematic review and meta-analysis. Heart rhythm, 18(12), 2128-2136.

Hindricks, G., Potpara, T., Dagres, N., Arbelo, E., Bax, J. J., Blomström-Lundqvist, C., Boriani, G., Castella, M., Dan, G. A., Dilaveris, P. E., Fauchier, L., Filippatos, G., Kalman, J. M., La Meir, M., Lane, D. A., Lebeau, J. P., Lettino, M., Lip, G., Pinto, F. J., Thomas, G. N., … ESC Scientific Document Group (2021). 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. European heart journal, 42(5), 373-498.

Gage, B. F., Eby, C., Johnson, J. A., Deych, E., Rieder, M. J., Ridker, P. M., Milligan, P. E., Grice, G., Lenzini, P., Rettie, A. E., Aquilante, C. L., Grosso, L., Marsh, S., Langaee, T., Farnett, L. E., Voora, D., Veenstra, D. L., Glynn, R. J., Barrett, A., & McLeod, H. L. (2008). Use of pharmacogenetic and clinical factors to predict the therapeutic dose of warfarin. Clinical pharmacology and therapeutics, 84(3), 326-331.

Heneghan, C., Tyndel, S., Bankhead, C., Wan, Y., Keeling, D., Perera, R., & Ward, A. (2010). Optimal loading dose for the initiation of warfarin: a systematic review. BMC cardiovascular disorders, 10, 18.

Kolesnyk, M. Yu., & Mykhailovskyi, Ya. M. (2021). Frequencies of polymorphisms in genes affecting the pharmacokinetics of warfarin in the Zaporizhzhia region. Zaporozhye medical journal, 23(4), 476-479.

Kolesnyk, M. Yu., & Mykhailovskyi, Ya. M. (2022). Efektyvnist i bezpechnist terapii warfarynom u khvorykh iz fibryliatsiieiu peredserd pid chas vyznachennia dozy farmakohenetychnym metodom [Efficacy and safety of warfarin therapy in patients with atrial fibrillation using genotype-guided dosing method]. Zaporozhye medical journal, 24(4), 390-395. [in Ukrainian].

Nehaj, F., Sokol, J., Ivankova, J., Mokan, M., Mokan, M., & Stasko, J. (2020). Edoxaban affects TRAP-dependent platelet aggregation. Journal of thrombosis and thrombolysis, 49(4), 578-583.

Bánovčin, P., Jr, Škorňová, I., Samoš, M., Schnierer, M., Bolek, T., Kovář, F., Staško, J., Kubisz, P., & Mokáň, M. (2017). Platelet Aggregation in Direct Oral Factor Xa Inhibitors-treated Patients with Atrial Fibrillation: A Pilot Study. Journal of cardiovascular pharmacology, 70(4), 263-266.

Ferreira, C. N., Vieira, L. M., Dusse, L. M., Reis, C. V., Amaral, C. F., Esteves, W. A., Fenelon, L. M., & Carvalho, M. G. (2002). Evaluation of the blood coagulation mechanism and platelet aggregation in individuals with mechanical or biological heart prostheses. Blood coagulation & fibrinolysis, 13(2), 129-134.

Mieszczak, C., & Winther, K. (1996). Does warfarin enhance platelet activity?. Thrombosis research, 84(4), 285-287.

Chylova, M., Motovska, Z., Fialova, A., Stetkarova, I., Peisker, T., & Kalvach, P. (2021). The effect of warfarin administration on platelet aggregation. Bratislavske lekarske listy, 122(5), 320-324.

S Markus H. (2020). D-dimer in ischemic stroke, and insights from HEADPOST into swallowing problems and outcome after stroke. International journal of stroke, 15(2), 121.

Ibebuogu, U. N., Schafer, J. H., Schwade, M. J., Waller, J. L., Sharma, G. K., & Robinson, V. (2020). Useful indices of thrombogenesis in the exclusion of intra-cardiac thrombus. Echocardiography, 37(1), 86-95.

Xu, Y., Wang, B., Jiang, L. J., Lu, X. P., Zhao, X. Y., & Wang, F. (2019). Roles of Microembolus and Plasma D-dimer in Evaluating the Warfarin Anticoagulant Therapy Efficacies for Patients with Atrial Fibrillation. The heart surgery forum, 22(1), E015-E018.



How to Cite

Kolesnyk MY, Mykhailovskyi YM. Platelet and coagulation hemostasis status in patients with atrial fibrillation depending on warfarin dosing method. Zaporozhye medical journal [Internet]. 2022Dec.20 [cited 2024Feb.24];24(6):647-51. Available from:



Original research