Predicting risks of prothrombotic readiness under COVID-19 using genetic testing

View or download the full article: 
PDF icon health-risk-analysis-2023-2-12.pdf
UDC: 
616.13+575.1
DOI: 
10.21668/health.risk/2023.2.12.eng
Authors: 

N.A. Vorobyeva, A.I. Vorobyeva, A.S. Vorontsova

Organization: 

Northern State Medical University, 51 Troitskii Ave., Arkhangelsk, 163000, Russian Federation

Abstract: 

COVID-19 poses a significant hazard as regards decompensation of underlying chronic diseases, specific damage to the cardiovascular system, and a high risk of negative health outcomes such as thrombotic events. The coronavirus infection pathogenesis is rather complicated and has not been studied yet; this is largely due to peculiar features of the virus and the initial state of homeostasis in a patient.
In this study, our aim was to analyze molecular-genetic markers of homeostasis in patients with the new coronavirus infection COVID-19 as a prognostic trigger of developing pro-thrombotic readiness.

Hospitalized patients with COVID-19 were chosen as study objects. We performed molecular-genetic analysis of basic genes significant for homeostasis including several factors such as V (rs6025), II (rs1799963), I (rs1800790), VII (rs6046), XIII A1 (rs5985)), IGN A2 (rs1126643), IGN B3 (rs5918), and PAI-1 (rs1799889). The thrombinemia severity was identified by thrombin generation tests using the Ceveron®alpha automated coagulation analyzer with TGA-module.

Allelic variants of PAI-1, prothrombin (FII), and fibrinogen (FI) determined high thrombinemia as per the thrombin kinetics test (endogenous thrombin potential (AUC), peak thrombin concentration (peak-thrombin), time necessary to reach thrombin peak (tPeak), levels of fibrinogen and D-dimer) in COVID-19 patients during the entire hospitalization. We established that elevated thrombin generation becoming apparent through elevated levels of endogenous thrombin potential (AUC) might be a prognostic indicator of the pro-thrombotic state in patients with genetic polymorphisms of PAI-I and fibrinogen.

The study results indicate that pro-thrombotic readiness is determined genetically in case COVID-19 patients have allelic variants in PAI-I, prothrombin (factor II) and fibrinogen (factor I) genes.

Keywords: 
COVID-19, genotype, risk, mutation, thrombinemia, polymorphism, thrombin, thrombosis
Vorobyeva N.A., Vorobyeva A.I., Vorontsova A.S. Predicting risks of prothrombotic readiness under COVID-19 using genetic testing. Health Risk Analysis, 2023, no. 2, pp. 130–139. DOI: 10.21668/health.risk/2023.2.12.eng
References: 
  1. Katsoularis I., Fonseca-Rodríguez O., Farrington P., Jerndal H., Häggström Lundevaller E., Sund M., Lindmark K., Fors Connolly A.-M. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: nationwide self-controlled cases series and matched cohort study. BMJ, 2022, vol. 377, pp. e069590. DOI: 10.1136/bmj-2021-069590
  2. Bikdeli B., Madhavan M.V., Jimenez D., Chuich T., Dreyfus I., Driggin E., Der Nigoghossian C., Ageno W. [et al.]. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up: JACC State-of-the-Art Review. J. Am. Coll. Cardiol., 2020, vol. 75, no. 23, pp. 2950–2973. DOI: 10.1016/j.jacc.2020.04.031
  3. Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S., Huang H., Zhang L. [et al.]. Risk factors associated with acute res-piratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med., 2020, vol. 180, no. 7, pp. 934–943. DOI: 10.1001/jamainternmed.2020.0994
  4. Soares M.P., Teixeira L., Moita L.F. Disease tolerance and immunity in host protection against infection. Nat. Rev. Immunol., 2017, vol. 17, no. 2, pp. 83–96. DOI: 10.1038/nri.2016.136
  5. Kabouridis P.S., Jury E.C. Lipid rafts and T-lymphocyte function: implications for autoimmunity. FEBS Lett., 2008, vol. 582, no. 27, pp. 3711–3718. DOI: 10.1016/j.febslet.2008.10.006
  6. Mannucci P.M., Franchini M. Classic thrombophilic gene variants. Thromb. Haemost., 2015, vol. 114, no. 5, pp. 885–889. DOI: 10.1160/TH15-02-0141
  7. Haralambous E., Hibberd M.L., Hermans P.W., Ninis N., Nadel S., Levin M. Role of functional plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism in susceptibility, severity, and outcome of meningococcal disease in Caucasian children. Crit. Care Med., 2003, vol. 31, no. 12, pp. 2788–2793. DOI: 10.1097/01.CCM.0000100122.57249.5D
  8. Wan Y., Shang J., Graham R., Baric R.S., Li F. Receptor recognition by the Novel Coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS Coronavirus. J. Virol., 2020, vol. 94, no. 7, pp. e00127-20. DOI: 10.1128/JVI.00127-20
  9. Varga Z., Flammer A.J., Steiger P., Haberecker M., Andermatt R., Zinkernagel A.S., Mehra M.R., Schuepbach R.A. [et al.]. Endothelial cell infection and endotheliitis in COVID-19. Lancet, 2020, vol. 395, no. 10234, pp. 1417–1418. DOI: 10.1016/S0140-6736(20)30937-5
  10. Moore J.B., June C.H. Cytokine release syndrome in severe COVID-19. Science, 2020, vol. 368, no. 6490, pp. 473–474. DOI: 10.1126/science.abb8925
  11. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G. [et al.]. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, vol. 395, no. 10223, pp. 497–506. DOI: 10.1016/S0140-6736(20)30183-5
  12. Vorobyova N.A., Nedashkovsky E.V. Optimization of intensive care in acute disseminated intravascular syndrome. Anesteziologiya i reanimatologiya, 2003, no. 4, pp. 50–54 (in Russian).
  13. Vorob'eva N.A. Mesto geneticheskikh polimorfizmov sistemy gemostaza v geneze trombofilicheskikh sostoyanii [Role of genetic polymorphisms of the hemostasis system in the genesis of thrombophilic conditions]. Arctic environmental research, 2004, no. 2 (6), pp. 14–21 (in Russian).
  14. Garred P., Strom J.J., Quist L., Taaning E., Madsen H.O. Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J. Infect. Dis., 2003, vol. 188, no. 9, pp. 1394–1403. DOI: 10.1086/379044
  15. Gordon A.C., Lagan A.L., Aganna E., Cheung L., Peters C.J., McDermott M.F., Millo J.L., Welsh K.I. [et al.]. TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study. Genes Immun., 2004, vol. 5, no. 8, pp. 631–640. DOI: 10.1038/sj.gene.6364136
  16. Vorobyova N.A., Kapustin S.I. Role of hemostatic system's genetic monitoring during serious proceeding of acute syndrome of disseminated intravascular coagulation. Ekologiya cheloveka, 2005, no. 12, pp. 25–30 (in Russian).
  17. The International Society on Thrombosis and Hemostasis (ISTH) interim guidance on recognition and management of coagulopathy in COVID-19: digest. Aterotromboz, 2020, no. 1, pp. 6–8. DOI: 10.21518/2307-1109-2020-1-6-8 (in Russian).
  18. Shatohin Yu.V., Snezhko I.V., Ryabikina E.V. Violation of hemostasis in coronavirus infection. Yuzhno-Rossiiskii zhurnal terapevticheskoi praktiki, 2021, vol. 2, no. 2, pp. 6–15. DOI: 10.21886/2712-8156-2021-2-2-6-15 (in Russian).
  19. Linkins L.A., Takach Lapner S. Review of D-dimer testing: good, bad, and ugly. Int. J. Lab. Hematol., 2017, vol. 39, suppl. 1, pp. 98–103. DOI: 10.1111/ijlh.12665
  20. Thachil J., Lippi G., Favaloro E.J. D-dimer testing: laboratory aspects and current issues // Methods Mol. Biol. – 2017. – Vol. 1646. – Р. 91–104. DOI: 10.1007/978-1-4939-7196-1_7
  21. Colucci G., Tsakiris D.A. Thrombophilia screening revisited: an issue of personalized medicine // J. Thromb. Throm-bolysis. – 2020. – Vol. 49, № 4. – P. 618–629. DOI: 10.1007/s11239-020-02090-y
  22. Hemker H.C., Al Dieri R., De Smedt E., Béguin S. Thrombin generation, a function test of the haemostatic-thrombotic system. Thromb. Haemost., 2006, vol. 96, no. 5, pp. 553–561.
  23. Carlier L., Hunault G., Lerolle N., Macchi L. Ex vivo thrombin generation patterns in septic patients with and without disseminated intravascular coagulation. Thromb. Res., 2015, vol. 135, no. 1, pp. 192–197. DOI: 10.1016/j.thromres.2014.11.001
Received: 
02.04.2023
Approved: 
18.05.2023
Accepted for publication: 
02.06.2023

You are here

Home