Optimization of anticoagulant therapy in elderly patients after viral infection COVID-19

The high incidence of thrombotic complications has led to the widespread use of anticoagulant therapy and prophylaxis in patients with COVID-19 after recovery. One of the most vulnerable groups of the population in relation to COVID-19 are elderly and senile people. The purpose of the study – analysis of literature data on the study of the effectiveness of the use of anticoagulant drags in elderly patients who have had a viral infection COVID-19, with a history burdened by concomitant pathology. The review presents literature data on the effectiveness of the use of anticoagulant therapy in elderly patients after mild or moderate COVID-19 against the background of various somatic diseases. To correct coagulation hemostasis disorders in clinical practice, both time-tested «classic» drags (heparin, warfarin), which require periodic monitoring of the international normalized ratio, and new oral anticoagulants from the group of direct thrombin inhibitors (dabigatran or Pradaxa^®) and the group of oral inhibitors of activated factor ten (Xa) activity – rivaroxaban (Xarelto^®), apixaban (Eliquis^®) and edoxaban (Lixiana^®, Savaysa^®, Roteas^®) – which have gained wide popularity. The article describes options for anticoagulant and antiplatelet therapy for elderly patients who have had coronaviras infection with various concomitant pathologies (hypertension, coronary heart disease, atherosclerotic cardiosclerosis, thrombosis of cerebral vessels, deep veins of the lower extremities, atrial fibrillation, conditions after stent placement). An analysis of the literature shows that doctors are concerned about the increased risk of thrombotic complications in the new coronaviras infection COVID-19. Early initiation and correct administration of anticoagulant therapy for COVID-19 are an undoubted factor in improving the prognosis in a group of elderly, somatically compromised patients. It has been established that direct oral anticoagulants for the treatment of thrombotic complications after COVID-19 in elderly patients with various comorbidities have a number of advantages over classic drags of this group. They are available, have a convenient method of administration, a regimen for determining and adjusting the dose, and do not require periodic monitoring of the international normalized ratio.

1. Profflaktika i lecheniye novoy koronavirasnoy infektsii (COVID-19). Vremennyye metodicheskiye rekomendatsii MZ RF. Versiya 15 = Prevention and treatment of a new coronaviras infection (COVID-19). Temporary methodological recommendations of the Ministry of Health of the Russian Federation. Version 15. 2022. 244 p. (In Russ.).

2. Recommendations for the management of patients with coronaviras infection COVID-19 in the acute phase and with post-COVID syndrome in outpatient settings. Ed. by prof. Vorobev P. A. Problemy standartizatsii v zdravookhranenii = Problems of standardization in healthcare. 2021; 7-8: 3-96. doi: 10.26347/1607-2502202107-08003-096 (In Russ.).

3. Moschonas I. C., Tselepis A. D. SARS-CoV-2 infection and thrombotic complications: a narrative review. Journal of Thrombosis and Thrombolysis. 2021; 52 (1): 111-123. doi: 10.1007/sll239-020-02374-3.

4. Menter T., Tzankov A. Investigations of pathologists as a key to understanding coronaviras disease 2019. Pathobiology. 2021; 88 (1): 11-14. doi: 10.1159/000513602.

5. Kipshidze N., Dangas G., White C. J., Siddiqui F., Lattimer C. R., Carter C. A., Fareed J. Viral coagulopathy in patients with COVID-19: Treatment and care. Clinical and Applied Thrombosis/Hemostasis. 2020; 26: 1076029620936776. doi: 10.1177/1076029620936776.

6. Kuznetsov S. I., Shestakov E. A., Zhiburt E. B. Coagulopathy in COVID-19 infection. Thrombosis, hemostasis, rheology. 2020; 4: 31-34. doi: 10.25555/THR.2020.4.0942 (In Russ.).

7. Labo N., Ohnuki H., Tosato G. Vasculopathy and coagulopathy associated with SARS-CoV-2 infection. Cells. 2020; 9 (7): 1583. doi: 10.3390/cells9071583.

8. del Rio C., Collins L. F., Malani P. Long-term health consequences of COVID-19. Journal of the American Medical Association. 2020; 324 (17): 1723-1724. doi: 10.1001/jama.2020.19719.

9. del Turco S., Vianello A., Ragusa R., Caselli C., Basta G. COVID-19 and cardiovascular consequences: Is the endothelial dysfunction the hardest challenge? Thrombosis Research. 2020; 196: 143-151.

10. Jordan R. E., Adab P., Cheng К. K. Covid-19: Risk factors for severe disease and death. British Medical Journal. 2020; 368: m l198. doi: 10.1136/bmj.mll98.

11. McGonagle D., ODonnell J. S., Sharif K., Emery P., Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatology. 2020; 2 (7): e437-e445. doi: 10.1016/S2665-9913(20)30121-1.

12. Recommendations of the Moscow City Healthcare Institution for the Diagnosis and Intensive Care of Disseminated Intravascular Coagulation Syndrome in Viral Lung Infection. Edited by Prof. Vorobev P. A. and Prof. Elykomov V. A. Problemy standartizatsii v zdravookhranenii = Problems of Standardization in Healthcare. 2020; 5-6. doi: 10.26347/1607-2502202005-06099-111 (In Russ.).

13. Lobastov К. V., Porembskaya O. Ya., Schastlivtsev I. V. Efficiency and Safety of Antithrombotic Therapy for COVID-19. Outpatient Surgeiy. 2021; 18 (2): 17-30. doi: 10.21518/1995-1477-2021-18-2 (In Russ.).

14. Jose R. J., Manuel A. COVID-19 cytokine storm: The interplay between inflammation and coagulation. Lancet Respiratory Medicine. 2020; 8 (6): e46-e47. doi: 10.1016/S2213-2600(20)30216-2.

15. Garunov Z. O., Zurkanaev S. A., Khizriev M. D., Shugaeva K.Y a. Modem anticoagulant therapy in the treatment of patients with new coronaviras infection. Mezhdunarodnyy zhumal meditsiny i psikhologii = International Journal of Medicine and Psychology. 2022; 5 (2): 139-141 (In Russ.).

16. Spyropoulos A. C., Weitz J. I. Hospitalized COVID-19 patients and venous thromboembolism. Circulation. 2020; 142 (2): 129-132. doi: 10.1161/CIRCULATIONAHA.120.048020.

17. Mehta P., McAuley D. F., Brown M. etal., Across Specialty Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395 (10229): 1033-4. doi: 10.1016/S0140-6736(20)30628-0.

18. Andrianto, Al-Farabi M. J., Nugraha A. R., Marsudi B. A, Azmi Y. Biomarkers of endothelial dysfunction and outcomes in coronaviras disease 2019 (COVID-19) patients: A systematic review and meta-analysis. Microvascular Research. 2021; 138: 104224. doi: https://doi.Org/10.1016/j.mvr.2021.104224.

19. Kastenhuber E. R., Jaimes J. A., Johnson J. L., Mercadante M., Muecksch F., Weisblum Y., Bram Y., Schwartz R. E., Whittaker G. R., Cantley L. C. Coagulation factors directly cleave SARS-CoV-2 spike and enhance viral entry. Preprint. BioRxiv, 2021.03.31.437960. doi: 10.1101/2021.03.31.437960.

20. Milling T. J. Jr, Frontera J. Exploring indications for the Use of direct oral anticoagulants and the associated risks of major bleeding. American Journal of Managed Care. 2017; 23 (4 Suppl): S67-S80.

21. Vorobyov P. A., Krasnova L. S., Vorobyov A. P. Three cases of effective anticoagulant remote therapy for COVID-19 infection in elderly patients with complicated somatic complications. Clinical Gerontology. 2022; 28 (5-6): 6-13 (In Russ.).

22. Ionova A. S., Skrebneva A. V., Melikhova E. P. Population aging and its demographic consequences. Rossiyskiy vestnik gigiyeny = Russian Bulletin of Hygiene. 2023; 1: 28-31. doi: 10.24075/rbh.2023.066 (In Russ.).

23. Konstantinov D. Yu., Popova L. L., Vasiliev S. Yu., Kurtov I. V., Davydkin I. L. Possibility of correction of anemia in a new coronavirus infection COVID-19. Astrakhanskiy meditsinskiy zhumal = Astrakhan Medical Journal. 2022; 17 (1): 30-34. doi: 10.48612/agmu/2022.17.1.30.34 (In Russ.).

24. Petrova О. V., Tverdokhlebova D. K., Shabanova G. R., Nikulina D. M., Shashin S. A. Analysis of the course of acute coronary syndrome after COVID-19. Astrakhanskiy meditsinskiy zhumal = Astrakhan Medical Journal. 2022; 17 (4): 100-108. doi: 10.48612/agmu/2022.17.4.100.108 (In Russ.).

25. Fang L., Karakiulakis G., Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respiratory Medicine. 2020; 8 (4): e21. doi: 10.1016/S2213-2600(20)30116-826.

26. Kamyshnyi A., Krynytska I., Matskevych V., Mamshchak M., Lushchak O. Arterial hypertension as a risk comorbidity associated with COVID-19 pathology. International Journal of Hypertension. 2020: 8019360. doi: 10.1155/2020/8019360.

27. Yavelov I. S. Prevention and treatment of venous thromboembolic complications: what a practicing physician needs to know. Clinical pharmacology and therapy. 2017; 26 (1): 17-23 (In Russ.).

28. Wichmann D., Sperhake J. P., Lutgehetmann M., Sterner S., Edler C., Heinemann A., Heinrich F., Mushumba H., Kniep I., Schroder A. S., Burdelski C., de Heer G., Nierhaus A., Frings D., Pfefferle S., Becker H., Bredereke-Wiedling H., de Weerth A., Paschen H. R., Sheikhzadeh-Eggers S., Stang A., Schmiedel S., Bokemeyer C., Addo M. M., Aepfelbacher M., Puschel K., Kluge S. Autopsy findings and venous thromboembolism in patients with COVID-19: A prospective cohort study. Annals of Internal Medicine. 2020; 173 (4): 268-277. doi: 10.7326/M20-2003.

29. Frydman G. H., Streiff M. B., Connors J. M., Piazza G. The potential role of coagulation factor Xa in the pathophysiology of COVID-19: a role for anticoagulants as multimodal therapeutic agents. TH Open. 2020; 4 (4): e288-e299. doi: 10.1055/s-0040-1718415.

30. Sriram K., Insel P. A. Inflammation and thrombosis in COVID-19 pathophysiology: proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets. Physiological Reviews. 2021; 101 (2): 545-567. doi: 10.1152/physrev.00035.2020.

31. Schmaier A. A., Schmaier A. H. Vascular disease patient information page: COVID-19-related thrombosis. Vascular Medicine. 2020; 25 (6): 604-607. doi: 10.1177/1358863X20963804.

32. Petrov V. I., Shatalova О. V., Stetsky N. P., Klykova M. S., Komissarova I. A. Use of oral anticoagulants inpatients with COVID-19: current concepts and contradictions. Bulletin of the Smolensk State Medical Academy. 2023; 22 (4): 56-63 (In Russ.).

33. RoytmanE. V., Bulanov A. Yu., Pechennikov V. M. Dosing of low molecular weight heparins and anti-factor Xa activity in patients with a new coronavirus infection COVID-19. Thrombosis, hemostasis and rheology. 2020; 4: 5767. doi: 10.25555/THR.2020.4.0946 (In Russ.).

34. Maltseva A. A., Smirnov A. A., Lukyanov M. M., Martsevich S. Yu., Kutishenko N. P., Pulin A. A., Drapkina О. M. Frequency of prescribing anticoagulant therapy to patients younger and older than 75 years with atrial fibrillation hospitalized with COVID-19. Preventive medicine. 2023; 26 (5-2): 23-24.

35. Gavrilenko L. N., Romanova I. S., Kozhanova I. N. Features of the use of anticoagulants in patients with COVID-19 infection. Retsept = Recipe. 2021; 24 (4): 584-588 (In Russ.).

36. Zaklyakova L. V., Ovsyannikova E. G., Kitiashvili I. Z., Zaklyakov К. K., Orlenko O. A., Burtseva N. B., Khaimina T. D. Heparin: modem issues of therapy. Astrakhanskiy meditsinskiy zhumal = Astrakhan Medical Journal. 2018; 13 (4): 14-22 (In Russ.).

37. Janssen R., Visser M. P. J., Dofferhoff A. S. M., Vermeer C., Janssens W., Walk J. Vitamin К metabolism as the potential missing link between lung damage and thromboembolism in coronavims disease 2019. British Journal of Nutrition. 2021; 126 (2): 191-198. doi: 10.1017/S0007114520003979.

38. Iba T., Levy J. H., Lev M., Thachil J. Coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis. 2020; 18 (9): 2103-2109. doi: 10.1111/jth.14975.

39. Matvienko O. Yu., Golovina O. G., Kobilyanskaya V. A., Smirnova O. A., Papayan L. P. The state of the hemostasis system in patients who have had a new coronavims infection. Efficiency of anticoagulant prophylaxis. Byulleten' meditsinskoy nauki = Bulletin of Medical Science. 2022; 3 (27): 30-36 (In Russ.).

40. Tomchenko A. I., Chechulova A. V., Soroka V. V., Nokhrin S. P., Khomchuk I. A. Risk of bleeding in elderly and senile patients with deep vein thrombosis of the lower extremities during anticoagulant therapy. Neotiozhnaya khirurgiya imeni 1.1. Dzhanelidze = Emergency surgery named after 1.1. Dzhanelidze. 2021; S2: 84 (In Russ.).

41. Moiseev S. V. Prevention of cardiovascular outcomes in patients with atrial fibrillation and diabetes mellitus: direct oral anticoagulants or warfarin? Klinicheskaya farmakologiya i terapiya = Clinical Pharmacology and Therapy. 2019; 28 (3): 5-13. doi: 10.32756/0869-5490-2019-3-5-13 (InRuss.).

42. Sina J., Geoffrey B. Stroke and thromboembolism prevention in atrial fibrillation. Heart. 2020; 106 (1): 10-17. doi: 10.1136/heartjnl-2019-314898.

43. Kanat Kyzy В . Adherence to the appointment of anticoagulant therapy with warfarin and rivaroxaban in elderly patients with atrial fibrillation in the Kyrgyz Republic. Meditsinskiy vestnik Bashkortostana = Medical Bulletin of Bashkortostan. 2021; 16, 3 (93): 42-46 (InRuss.).

44. Smagina A. N., Sheshina N. A., Zhuk A. A., Shuldyakov A. A., Kimosova O. A. Remote consequences of the use of anticoagulants in patients with COVID-19. Georgiyevskiy chteniya: Nasledstvennaya i priobretennaya patologiya svertyvaniya krovi - trombozy i krovotecheniya (diagnostika, profilaktika, lecheniye) = Georgievskiy readings: Hereditary and acquired pathology of blood coagulation - thrombosis and bleeding (diagnosis, prevention, treatment). Ed. by D. M. Puchinyan, S. S. Parshina. Saratov: Saratovskiy istochnik; 2022. 116 p. (In Russ.).

45. Shcheglov E. A., Alontseva N. N. Safety of anticoagulant use in patients with acute arterial ischemia // Angiology and vascular surgery. Angiologiya i sosudistaya khirurgiya. Zhurnal imeni akademika A. V. Pokrovskogo = Journal named after academician A. V. Pokrovsky. 2022; 28 (SI): 296-297 (In Russ.).

46. Zolotovskaya I. A., Sabanova V. D., Davydkin I. L. Possibilities of anticoagulant therapy in the most vulnerable groups of patients. Literature review. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021; 26 (S4): 44-52. doi: 10.15829/1560-4071-2021-4786 (In Russ.).

47. Davtyan P. A., Gumerov R. M., Zagidullin Sh. Z., Samorodov A. V., Tsai B., Zagidullin N. Sh. Is anticoagulant therapy necessary after discharge from hospital with COVID-19-associated pneumonia? Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021; 26 (S4): 4652. doi: 10.15829/1560-4071-2021-4652 (In Russ.).