Change of hematological parameters in COVID-19

The new coronavirus infection, which has caused significant morbidity and mortality in most countries of the world, was first identified in December 2019 in Wuhan, China. In March 2020, the World Health Organization declared a pandemic of a new coronavirus infection, which became a challenge to humanity and the medical community. COVID-19 is a highly contagious disease caused by the SARS-CoV-2 virus. Specific prothrombotic changes in the hemostasis system in COVID-19 are associated with an increased incidence of venous thromboembolic complications. One of the most dangerous and prognostically unfavorable complications of COVID-19 is the development of coagulopathy of the type of decompensated hypercoagulation, up to disseminated intravascular coagulation. There is a close relationship between hemostatic disorders and the systemic inflammatory response to viral infection. Clinical and laboratory signs of thrombotic conditions and their severity are directly correlated with the production of inflammatory cytokines: IL-2, IL-6, IL-7, IL-10, G-CSF, IP10, MCP-1, MIP-1A and TNF-α. The 

relationship between inflammation and thrombosis and the ability of these two processes to exacerbate each other have been described in many pathological conditions. Physiological pro- and anticoagulants, like platelets, have pro-inflammatory properties independent of their hemostatic functions. Mutual conditioning of thrombotic complications and systemic inflammatory response is one of the main links in the pathogenesis of COVID-19. COVID-19 associated coagulopathy is accompanied by a pronounced increase in the level of D-dimer and fibrin/fibrinogen breakdown products, while the deviation of other indicators (prothrombin time, activated partial thromboplastin time, platelet count) at the onset of the disease is relatively rare. For coagulopathy associated with COVID-19, empiric anticoagulant therapy aimed at preventing venous thrombosis and thromboembolism should be carried out in all hospitalized patients, as well as standard maintenance therapy for sepsis-induced coagulopathy or disseminated intravascular coagulation syndrome. The article is a review of the literature on the diagnosis, treatment and prevention of coagulopathy and venous thromboembolic complications associated with COVID-19.

1. Bovt E. A., Brazhnik V. A., Bulanov A. Yu., Vasilyeva E. Yu., Vuimo T. A., Zateishchikov D. A., Rumyantsev A. G. Results of multicenter monitoring of hemostasis parameters in COVID-19 patients // Pediatriya. 2020; 6 (96).

2. Wichmann D., Sperhake J. P., Lutgehetmann M., Steurer S., Edler C., Heinemann A., et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19 // Ann Intern Med. 2020; 173 (4): 268-277. DOI: 10.7326/M20-2003.

3. Barnes G. D., Burnett A., Allen A., Blumenstein M., Clark N. P., Cuker A., et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum // J Thromb Thrombolysis. 2020; 50 (1): 72-81. DOI: 10.1007/s11239-02002138-z.

4. Fox S. E., Akmatbekov A., Harbert J. L., Li G., Quincy Brown J., Vander Heide R.S. Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans // The Lancet Respiratory Medicine. 2020; 8 (7): 681-686. DOI: 10.1016/s2213-2600 (20)30243-5.

5. Han H., Yang L., Liu R., Liu F., Wu K.L., Li J., et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection // Clin Chem Lab Med. 2020; 58 (7): 1116-1120. DOI: 10.1515/cclm-2020-0188.

6. Bowles L., Platton S., Yartey N., Dave M., Lee K., Hart D.P., et al. Lupus Anticoagulant and Abnormal Coagulation Tests in Patients with Covid-19 // New England Journal of Medicine. 2020; 383 (3): 288-290. DOI: 10.1056/NEJMc2013656.

7. Lodigiani C., Iapichino G., Carenzo L., Cecconi M., Ferrazzi P., Sebastian T., et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy // Thromb Res. 2020; 191: 9-14. DOI: 10.1016/j.thromres.2020.04.024.

8. Xu Z., Shi L., Wang Y., Zhang J., Huang L., Zhang C., et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome // Lancet Respir Med. 2020; 8 (4): 420-422. DOI: 10.1016/S2213-2600(20)30076-X.

9. Fogarty H., Townsend L., et al. Persistent endotheliopathy in the pathogenesis of long COVID syndrome // J Thromb Haemost. 2021; 19 (10): 2546-2553. DOI: 10.1111/jth.15490.

10. Lax S. F., Skok K., Zechner P., Kessler H. H., Kaufmann N., Koelblinger C., et al. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series // Ann Intern Med. 2020; 173 (5): 350-361. DOI: 10.7326/M20-2566.

11. Panigada M., Bottino N., Tagliabue P., Grasselli G., Novembrino C., Chantarangkul V., et al. Hypercoagulability of COVID-19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis // J Thromb Haemost. 2020; 18 (7): 1738-1742. DOI: 10.1111/jth.14850.

12. Cao W., Li T. COVID-19: towards understanding of pathogenesis // Cell Research. 2020; 30 (5): 367-369. DOI: 10.1038/s41422-020-0327-4.

13. Liu X., Zhang X., Xiao Y., Gao T., Wang G., Wang Z., et al. Heparin-induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment // MedRxiv. 2020. DOI: 10.1101/2020.04.23.20076851.

14. Omarova D. A., Mammaev S. N., Karimova A. M. On the diagnosis of DIC syndrome in COVID-19 // Vestnik Dagestanskoi gosudarstvennoi medicinskoi akademii. 2021; 2 (39): 48-53. EDN NKCLYD.

15. Tian S., Xiong Y., Liu H., Niu L., Guo J., Liao M., et al. Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies // Mod Pathol. 2020; 33 (6): 1007-1014. DOI: 10.1038/s41379-020-0536-x.

16. Becker R. C. COVID-19 update: COVID-19-associated coagulopathy // J Thromb Thrombolysis. 2020; 50: 54-67. DOI: 10.1007/s11239-020-02134-3.

17. Di Micco P., Russo V., Carannante N., Imparato M., Rodolfi S., Cardillo G., et al. Clotting Factors in COVID-19: Epidemiological Association and Prognostic Values in Different Clinical Presentations in an Italian Cohort // J Clin Med. 2020; 9 (5): 1371. DOI: 10.3390/jcm9051371.

18. Carsana L., Sonzogni A., Nasr A., Rossi R., Pellegrinelli A., Zerbi P., et al. Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy // medRxiv. 2020. DOI: 10.1101/2020.04.19.20054262.

19. Helms J., Tacquard C., Severac F., Leonard-Lorant I., Ohana M., Delabranche X., Merdji H., Clere-Jehl R., Schenck M., Gandet F. F., Faf-Kremer S., Castelain V., Schneider F., Grunebaum L., Anglés-Cano E., Sattler L., Mertes P. M., Meziani F.; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Re# search in Sepsis). High risk of thrombosis in patients with se# vere SARS-CoV-2 infection: a multicenter prospective cohort study // Intensive Care Medicine. 2020; 46 (6): 1089-1098.

20. Thachil J. The versatile heparin in COVID-19 // Journal of Thrombosis and Haemostasis. 2020; 18 (5): 1020-1022.

21. F. A., Kruip M. J. H. A., van der Meer N. J. M., Arbous M. S., Gommers D. A. M. P. J., Kant K. M., Kaptein F. H. J., van Paassen J., Stals M. A. M., Huisman M. V., Endeman H. Incidence of thrombot# ic complications in critically ill ICU patients with COVID-19 // Thrombosis Research. 2020; 191: 145-147.

22. Barnes G. D., Burnett A., Allen A., Blumenstein M., Clark N. P., Cuker A., Dager W. E., Deitelzweig S. B., Ellsworth S., Garcia D., Kaatz S., Minichiello T. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guid# ance from the anticoagulation forum // Journal of Thrombosis and Thrombolysis. 2020; 50 (1): 72-81.

23. Goshua G., Pine A. B., Meizlish M. L., et al. Endotheliopathy in COVID19-associated coagulopathy: evidence from a single-centre, cross-sectional study // Lancet Haematol. 2020; 7 (8): e575-e582. DOI: 10.1016/S2352-3026(20)30216-7.