Application of Raman spectroscopy using an original optical sensor to assess the laboratory efficacy of antiplatelet drugs

The main method for monitoring the laboratory effectiveness of antiplatelet drugs in modern clinical practice is aggregometry, but this method is not without limitations. In this connection, there is an objective need to develop alternative methods. One of the promising areas is the method of Raman spectroscopy (RS).

Objective: development of a method to detect high residual platelet reactivity (RPR) in patients with CVD receiving acetylsalicylic acid (ASA) or clopidogrel by giant Raman spectroscopy (GRS) using an original optical biosensor.

Material sand Methods. Platelet-rich plasma of patients with cardiovascular diseases (CVD) was investigated by Raman spectroscopy using an original optical biosensor. Platelet aggregation activity was investigated using a Siemens PFA-200 aggregometer with three types of cartridges – Collagen/EPI, Collagen/ADP, and P2Y. Fisher’s linear discriminant analysis was performed using Statistica 13.0 package.

Results. Raman spectra analysis using different values of frequency shifts (970 cm-1 or 1590 cm-1), allows to evaluate laboratory ineffectiveness separately for ASA and clopidogrel. Thus, the number of patients with high residual platelet reactivity (RPR) was 41.7 % ± 6.3 % with ASA and 36.7 % ± 6.2 % with clopidogrel therapy; similar values using aggregometry were 43.5 % ± 10.3 % and 30.4 % ± 9.6 %.

Conclusion. Application of the method of Raman spectroscopy using the original optical biosensor allows to distinguish patients with high RPR in the population of patients with CVD receiving antiaggregant therapy.

1. Timmis A., Vardas P., Townsend N., Torbica A., Katus H., De Smedt D., et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022;43(8):716–99. doi: 10.1093/eurheartj/ehab892. PMID: 35016208

2. Bezverkhov A., Ishchenko O. Dynamics of mortality from cardiovascular diseases for the period 2015–2019. Norwegian Journal of Development of the International Science. 2021(54–2):35–8. (In Russ.). doi: 10.24412/3453-9875-2021-54-2-35-38

3. Boytsov S., Pogosova N., Ansheles A., Badtieva V., Balakhonova T., Barbarash O., et al. Cardiovascular prevention 2022. Russian national recommendations. Russian journal of cardiology. 2023;28(5):119–249. (In Russ.). doi: 10.15829/1560-4071-2023-5452

4. Goncharov, M.D., Grinshtein Yu.I., Savchenko A. A. Features of the production of reactive oxygen species by platelets and neutrophils in the formation of an insufficient response to acetylsalicylic acid in patients with coronary heart disease after coronary artery bypass grafting. Translational Medicine 9.1 (2022): 12–28. (In Russ.). doi: 10.18705/2311-449-2022-9-1-12-28

5. Kantemirova B. I., Orlova E. A., Polunina O. S., Chernysheva E. N., Abdullaev M. A., Sychev D. A. Pharmacogenetic bases of individual sensitivity and personalized prescription of antiplatelet therapy in different ethnic groups. Pharmacy and pharmacology. 2020;8(6):392–404. doi: 10.19163/2307-9266-2020-8-6-392-404

6. Sidorov A. Antithrombotic effect of acetylsalicylic acid preparations in different dosage forms: is there a difference? Russian Journal of Cardiology. 2021 (10): 127–42. (In Russ.). doi: 10.15829/1560-4071-2021-4734

7. Hochholzer, W. Whole blood aggregometry for evaluation of the antiplatelet effects of clopidogrel / W. Hochholzer, D. Trenk, D. Frundi et al. // Thrombosis research.– 2007.– Т. 119.– № . 3.– С. 285–291. doi: 10.1016/j.thromres.2006.02.007

8. Khabirova A., Litvinov R. Contribution of platelet contractility to laboratory parameters characterizing platelet function. Clinical laboratory diagnostics. 2023; 68 (9). (In Russ.). doi: 10.51620/0869-2084-2023-68-9–447-454-544-552

9. Salukhov V., Gulyaev N., Chepel A., Zemlyanoy A., Dorokhina E. Prevention of coronary heart disease complications with variable platelet response. Bulletin of the Pirogov National Medical and Surgical Center. 2020;15(4):82–90. doi:10.25881/BPNMSC.2020.20.88.016

10. Matveeva K. I., Kundalevich A. A., Kapitunova A. I., Zozulya A. S., Sukhikh S. A., Tsibulnikova A. V., Samusev I. G., Raman spectroscopy in studies of bacterial microorganisms inactivation processes. Scientific and Technical Bulletin of Information Technologies, Mechanics and Optics, 23(4), 676–684. doi: 10.17586/2226-1494-2023-23-4-676-684

11. Schlucker S. Surface-Enhanced raman spectroscopy: Concepts and chemical applications. Angewandte Chemie International Edition, 53(19), 4756–4795. doi: 10.1002/anie.201205748

12. Pavlov V. N., Gil’manova R.F., Korolev V. V., Urmancev M. F. Differential diagnostics of muscle-invasive and muscle-noninvasive bladder cancer using Raman spectroscopy (RAMAN spectroscopy). Malignant tumors, 10(3S 1), 91–91. (In Russ.).

13. Conroy R. M., Pyörälä K., Fitzgerald A. E., Sans S., Menotti A., De Backer G., Graham I. M. (2003). Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. European heart journal, 24(11), 987-1003. doi: 10.1016/s0195–668x(03)00114–3

14. Zyubin A., Rafalskiy V., Lopatin M., Demishkevich E., Moiseeva E., Matveeva K., Bryukhanov V. (2022). Spectral homogeneity of human platelets investigated by SERS. Plos one, 17(5), e0265247. doi: 10.1371/journal.pone.0265247

15. Zyubin A. Yu., Rafal’skiy V.V., Moiseeva E. M. [et al.] Patent No. 2788479 C 1 Russian Federation, IPC G01N 21/41, B 82B 1/00. Planar nanostructured sensor based on surface plasmon resonance for enhancing Raman scattering of human platelets and a method for producing it: No. 2022108969: declared 04.04.2022: published 19.01.2023; applicant Federal State Autonomous Educational Institution of Higher Education “Immanuel Kant Baltic Federal University”.– EDN PUBVLJ. 19.01.2023. (In Russ.).

16. Moiseeva E., Rafal’skiy V., Sokolov A., Zyubin A., Bychkova Ya., Samusev I. Use of giant Raman spectroscopy to search for pharmacodynamic predictors of response to antiplatelet therapy. Siberian Journal of Clinical and Experimental Medicine. 2023;38(3):185–93. (In Russ.). doi: 10.29001/2073-8552-2022-538

17. Panteleev M. A., Ataullakhanov, F.I. (2008). Blood coagulation: biochemical basis. Clinical oncohematology. Fundamental research and clinical practice, 1(1), 50–62. (In Russ.).

18. Andryukov B. G., Lyapun I., Bynina M., Matosova E. Simplified formats of modern biosensors: 60 years of using immunochromatographic test systems in laboratory diagnostics. Clinical laboratory diagnostics. 2020;65(10):611–8. (In Russ.). doi: 10.18821/0869-2084-2020-65-10-611-618

19. Mirzaev K. B., Andreev D. A., Sychev D. A. Evaluation of platelet aggregation in clinical practice. Rational pharmacotherapy in cardiology. 2015;11(1):85–91. (In Russ.). doi:10.20996/1819-6446-2015-11-1-85-91

20. Chen Q., Wu W., Wang K., Han Z., Yang C. Methods for detecting of cardiac troponin I biomarkers for myocardial infarction using biosensors: a narrative review of recent research. J Thorac Dis. 2023;15(9):5112–21. doi: 10.21037/jtd-23–1263