ISSN 2410-7751 (Print)
ISSN 2410-776X (Online)
Biotechnologia Acta V. 15, No. 3, 2022
P. 52-57. Bibliography 19, Engl.
UDC: 577.151:612.115
https://doi.org/10.15407/biotech15.03.052
1 Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv
2 State Institute "Shalimov`s national institute of surgery and transplantation" to national academy of medikal sciences of Ukraine, Kyiv
Aim. Treatment by indirect anticoagulants (vitamin K antagonists) requires a personalized approach for controlling the overall level of prothrombin and the accumulation of its decarboxylated forms. The purpose of this work was to optimize the method for monitoring of the therapy with indirect anticoagulants.
Methods. An analysis was performed of 41 blood plasma samples from patients with cardiovascula pathologies. Activated partial thromboplastin time (APTT), prothrombin time, ecamulin time, statistical data analysis (“Statistica 7”) have been used.
Results. APTT test allowed identifying the individual sensitivity of patients to indirect anticoagulants. In particular, 20% of patients showed a decrease in the total level of prothrombin, which, together with the accumulation of decarboxylated forms, leads to a risk of bleeding. Individual insensitivity to the action of vitamin K antagonists was determined in 11% of patients.
Conclusion. To control the efficacy of indirect anticoagulants therapy, we developed test in which ecamulin (protease from the venom of Echis multisquamatis) was used as a prothrombin activator, which can activate not only functionally active prothrombin, but also its decarboxylated forms. Use of ecamulin simultaneously with thromboplastin allows determining in the blood plasma the content of not only functionally active prothrombin, but also the total level of prothrombin, which makes it possible to control the accumulation of decarboxylated prothrombin.
Key words: prothrombin, vitamin K, indirect anticoagulants, thrombolytic therapy.
© Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2022
References
1. Grober U., Reichrath J., Holick M. F., Kisters K. Vitamin K: an old vitamin in a new perspective Dermatoendocrinol. 2015, 6(1), e968490. https://doi.org/10.4161/19381972.2014.968490
2. Zirlik A., Bode C. Vitamin K antagonists: relative strengths and weaknesses vs. direct oral anticoagulants for stroke prevention in patients with atrial fibrillation. J Thromb Thrombolysis. 2017; 43(3): 365–379. https://doi.org/10.1007/s11239-016-1446-0
3. Alquwaizani M., Buckley L., Adams C., Fanikos J. Anticoagulants: A Review of the Pharmacology, Dosing, and Complications. Curr Emerg Hosp Med Rep. 2013, 1(2), 83–97. https://doi.org/10.1007/s40138-013-0014-6
4. Oscar M. P. Jolobe. A comparison between vitamin K antagonists and new oral anticoagulants. Br J Clin Pharmacol. 2017, 83(11), 2589–2590. https://doi.org/10.1111/bcp.13347
5. Lipatova N. A., Titaeva E. V., Dobrovolskii A. B. Antagonisty vitamina K: mekhanizm anticoaguljantnogo deistvii I laboratornyij control terapii. Klin. Lab. Diagnostika. 2006, 5, 25?33 (In Ukrainian).
6. Brenner B., Kuperman A., Watzka M., Oldenburg J. Vitamin K-dependent coagulation factors deficiency. Semin. Thromb. Hemost. 2009, 35(4), 439-46. https://doi.org/10.1055/s-0029-1225766
7. Margueritta S. El Asmar, Naoum J. J., Arbid E. J. Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation of Vascular Calcification: A Review. Oman Medical Journal. 2014, 29(3), 172-77. https://doi.org/10.5001/omj.2014.44
8. Dolgov V. V., Svirin P. V. Laboratornaja diagnostika naryshenij hemostaza. М.-Tver: ООО «Izdatelstvo “Triada”, 2005. – 227 s (In Russian).
9. Solovjov D. A, Platonova T. N., Ugarova T. P. Purification and characterization of ecamulin - a new prothrombin activator from the Echis multisquamatus snake venom. Biochemistry (Mosc). 1996, 61(6), 785?93.
10. Castellone D. D., Van Cott E. M. Laboratory monitoring of new anticoagulants. Am. J. Hematol. 2010, 85,185?87. https://doi.org/10.1002/ajh.21607
11. Geoffrey Kershaw, Emmanuel J. Favaloro. Laboratory identification of factor inhibitors: an update. Pathology. 2012; 44(4), 293?302. https://doi.org/10.1097/PAT.0b013e328353254d
12. Gryschenko V. A., Tomchuk V. A., Lytvynenko O. N., Chernyshenko V. O., Gryschuk V. I., Platonova T. M. An estimate of protein synthesis in liver under induced hepatitis. Ukr. Biochem. Journ. 2011, 83(1), 63–8.
13. Danciger J. Vitamin K-dependent Proteins, Warfarin, and Vascular Calcification. Clin. J. Am. Soc. Nephrol. 2008, 3, 1504?10. https://doi.org/10.2215/CJN.14180920
14. B. T. Samuelson, A. Cuker. Measurement and reversal of the direct oral anticoagulants. Blood Rev. 2017, 31(1), 77-84. https://doi.org/10.1016/j.blre.2019.100593.
15. Kini R. M. The intriguing world of prothrombin activators from snake venom. Toxicon. 2005, 45, 1133-1141. https://doi.org/10.1016/j.toxicon.2005.02.019
16. Korolova D. S., Vinogradova R. P., Chernyshenko T. M., Platonova T. M., Volkov G. L. Vykorystannja ekamulinu z otytu efu bagatolyskovoi v klinichnij laborotornij praktuci. Lab. diagnostika. 2006, 37(3), 18?22. (In Ukrainian).
17. Korolova D. S., Deev V. A., Kypovska S. I., Chernyshenko T. M., Platonova T. M., Lugovskoj E. V. Vuznachennja funkcionalno neaktuvnuh form protrombinu dlja kontrolju efektivnosti likuvannja antikoaguljantami neprjamoi dii. Lab. diagnostika. 2009; 2(48):3-12.
18. Lori-Ann Linkins. Bleeding risks associated with vitamin K antagonists Blood Reviews.2013, 27, 111–118. https://doi.org/10.1016/j.blre.2013.02.004
19. Haug K.B.F., Sharikabad M.N., Kringen M Sigrid Narum, Stine T Sjaatil, Per Wiik Johansen, Peter Kierulf, Ingebj?rg Seljeflot, Harald Arnesen, Odd Br?rs. Warfarin dose and INR related to genotype of CYP2C9 and VKORCI in patients with miocardial infarction. Thromb. J. 2008, 6(7), 557?62. https://doi.org/10.1186/1477-9560-6-7