Thrombosis and endogenous fibrinolysis in the deferred period of myocardial infarction

Authors: Kalinskaya A.I, Dukhin O.A., Uzhakhova Kh.M., Vasilieva E.Yu., Shpektor A.V.

Company: Department of Cardiology of Moscow State University of Medicine and Dentistry named after A.I. Evdokimov, Moscow, 127473, Russian Federation

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Type:  Original articles


For citation: Kalinskaya A.I., Dukhin O.A., Uzhakhova Kh.M., Vasilieva E.Yu., Shpektor A.V. Thrombosis and endogenous fibrinolysis in the deferred period of myocardial infarction. Creative Cardiology. 2020; 14 (1): 24–34 (in Russ.). DOI: 10.24022/1997-3187-2020-14-1-24-34

Received / Accepted:  05.03.2020 / 14.03.2020

Keywords: endogenous fibrinolysis myocardial infarction thrombosis spontaneous reperfusion

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Objective: to evaluate the processes of thrombosis and endogenous fibrinolysis in patients with a history of ST-segment elevation myocardial infarction (STEMI).
Material and methods. 102 participants were included in the study: 51 patients (19 with spontaneous reperfusion (SR) of infarct-related artery (IRA) during coronary angiography, 32 with total occlusion) and 51 healthy volunteers. The parameters of hemostasis were evaluated using rotational thromboelastometry and thrombodynamics, endothelial function – using the flow-mediated dilation test (FMD) test, all patients underwent echocardiography.
Results. Patients with a history of STEMI are characterized by faster clot formation (CT, with 720 [625; 850] s vs 810 [699; 940] s, p = 0.01), larger clot size at various stages of the experiment (angle α 49 [46; 59]° vs 44 [39; 55], p < 0.01; A10, mm (41 [39; 49] vs 36 [33; 42], p < 0.01); A20 (52 [50; 57] mm vs 50 [44; 53], p = 0.01), earlier onset of clot lysis (LOT (38.0 [30.8; 53.7] min vs 65.3 [42.9; 79.3], p < 0.01) compared to healthy volunteers. Patients with a history of IRA occlusion had a faster clot growth rate (V (28.1 [26.3; 35.0] μm/min vs 31.9 [30.2; 38.8], p < 0.01), a larger clot size (CS 1190.5 [1160; 1292] μm vs 1315 [1204; 1458], p < 0.01), reduced flow-mediated
dilation test (FMD test 11.6 [8.4; 13.1]% vs 17.3 [14.4; 20.0], p < 0.01) and ejection fraction of the left ventricle (EF, % 55 [52; 60]% vs 62.0 [57.5; 64.0], p < 0.01) compared to patients with SR of IRA during coronary angiography.
Conclusion. Patients with myocardial infarction are characterized by increased activation of clotting and endogenous fibrinolysis compared with healthy volunteers. Among patients with IRA occlusion the clotting remains increased to a greater extent in comparison to patients with a history of SR of IRA.


  1. Reddel C.J., Curnow J.L., Voitl J. et al. Detection of hypofibrinolysis in stable coronary artery disease using the overall haemostatic potential assay. Thromb. Res. 2013; 131 (5): 457–62. DOI: 10.1016/j.thromres.2013.03.015
  2. Urazovskaya I.L., Skrypnik D.V., Vasilieva E.Yu., Shpektor A.V. The effect of endothelial status on the possibility of spontaneous thrombolysis in patients with ST-elevation myocardial infarction. Creative Cardiology. 2008; 2 (1): 36–8 (in Russ.).
  3. Badings E.A., Remkes W.S., Salem H.K. et al. Early or late intervention in patients with transient ST-segment elevation acute coronary syndrome: Subgroup analysis of the ELISA-3 trial. Catheter. Cardiovasc. Interv. 2016; 88 (5): 755–64. DOI: 10.1002/ccd.26719
  4. Fefer P., Beigel R., Atar S. et al. Outcomes of patients presenting with clinical indices of spontaneous reperfusion in ST-elevation acute coronary syndrome undergoing deferred angiography. J. Am. Heart Assoc. 2017; 6 (7). DOI: 10.1161/JAHA.116.004552
  5. Lemkes J.S., Janssens G.N., van der Hoeven N.W. et al. Timing of revascularization in patients with transient ST-segment elevation myocardial infarction: a randomized clinical trial. Eur. Heart J. 2019; 40 (3): 283–91. DOI: 10.1093/eurheartj/ehy651
  6. Savvinova P.P., Kalinskaya A.I., Manchurov V.N., Anisimov K.V., Vasilieva E.Yu., Shpektor A.V. Coronary angiogram and laboratory parameters of blood clot formation and lysis correlation in patients with acute coronary syndrome. Russian Journal of Endovascular Surgery. 2019; 6 (3): 207–13 (in Russ.).
  7. Thygesen K., Alpert J.S., Jaffe A.S. et al. Fourth universal definition of myocardial infarction (2018). Circulation. 2018; 138 (20): e618–51. DOI: 10.1161/CIR.0000000000000617
  8. Meesters M.I., Koch A., Kuiper G., Zacharowski K., Boer C. Instability of the non-activated rotational thromboelastometry assay (NATEM) in citrate stored blood. Thromb. Res. 2015; 136 (2): 481–3. DOI: 10.1016/j.thromres.2015.05.026
  9. Balandina A.N., Koltsova E.M., Shibeko A.M., Kuprash A.D., Ataullakhanov F.I. Thrombodynamics: a new method to the diagnosis of hemostasis system disorders. Pediatr. Hematol. Immunopathol. 2018; 17 (4): 114–26. DOI: 10.24287/1726-1708-2018-17-4-114-126
  10. Kalinskaya A.I., Savvinova P.P., Vasilieva E.Yu., Shpektor A.V. The specifics of clotting and endogenic fibrinolysis in acute coronary syndrome patients. Russ. J. Cardiol. 2018; 23 (9): 12–6. DOI: 10.15829/1560-4071-2018-9-12-16
  11. Tuktamyshov R., Zhdanov R. The method of in vivo evaluation of hemostasis: spatial thrombodynamics. Hematology. 2015; 20 (10): 584–6. DOI: 10.1179/1607845415Y.0000000022
  12. Shlyk I.F. Informativeness of the thrombodynamic method in assessing the state of hemostasis in patients with coronary heart disease. Med. Her. South. Russ. 2019; 10 (2): 48–54. DOI: 10.21886/2219-8075-2019-10-2-48-54
  13. Badimon L., Vilahur G. Thrombosis formation on atherosclerotic lesions and plaque rupture. J. Intern. Med. 2014; 276 (6): 618–32. DOI: 10.1111/joim.12296
  14. Di Serafino L., Sarma J., Dierickx K. et al.Monocyte-platelets aggregates as cellular biomarker of endothelium-dependent coronary vasomotor dysfunction in patients with coronary artery disease. J. Cardiovasc. Transl. Res. 2014; 7 (1): 1–8. DOI: 10.1007/s12265-013-9520-x
  15. Pinegina N.V. Leukocyte-platelet complexes in the pathogenesis of acute coronary syndrome. Part 2. Creative Cardiology. 2016; 10 (3): 201–9 (in Russ.)
  16. Loguinova M., Pinegina N., Kogan V. et al. Monocytes of different subsets in complexes with platelets in patients with myocardial infarction. Thromb. Haemost. 2018; 118 (11): 1969–81. DOI: 10.1055/s-0038-1673342
  17. Gimbrone M.A., García-Cardeña G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 2016; 118 (4): 620–36. DOI: 10.1161/CIRCRESAHA.115.306301
  18. Borissoff J.I., Spronk H.M.H., ten Cate H. The hemostatic system as a modulator of atherosclerosis. N. Engl. J. Med. 2011; 364 (18): 1746–60. DOI: 10.1056/NEJMra1011670
  19. Hyseni A., Roest M., Braun S.L. et al. Chronic dysfunction of the endothelium is associated with mortality in acute coronary syndrome patients. Thromb. Res. 2013; 131 (3): 198–203. DOI: 10.1016/j.thromres.2012.12.001
  20. Thanyasiri P., Celermajer D.S., Adams M.R. Endothelial dysfunction occurs in peripheral circulation in patients with acute and stable coronary artery disease. Am. J. Physiol. Hear Circ. Physiol. 2005; 289 (2): H513–7. DOI: 10.1152/ajpheart.01086.2004
  21. Li J., Zhou Y., Zhang Y., Zheng J. Admission homocysteine is an independent predictor of spontaneous reperfusion and early infarct-related artery patency before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. BMC Cardiovasc. Disord. 2018; 18 (1). DOI: 10.1186/s12872-018-0868-3
  22. Sabra A., Lawrence M.J., Aubrey R. et al. Characterisation of clot microstructure properties in stable coronary artery disease. Open Hear. 2017; 4 (2): e000562. DOI: 10.1136/openhrt-2016-000562
  23. Kreutz R.P., Bitar A., Owens J. et al. Factor XIII Val34Leu polymorphism and recurrent myocardial infarction in patients with coronary artery disease. J. Thromb. Thrombolysis. 2014; 38 (3): 380–7. DOI: 10.1007/s11239-014-1059-4
  24. Lim S.L., Lam C.S.P., Segers V.F.M., Brutsaert D.L., De Keulenaer G.W. Cardiac endothelium-myocyte interaction: Clinical opportunities for new heart failure therapies regardless of ejection fraction. Eur. Heart J. 2015; 36 (31): 2050–60. DOI: 10.1093/eurheartj/ehv132
  25. Casas J.P., Bautista L.E., Humphries S.E., Hingorani A.D. Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23 028 subjects. Circulation. 2004; 109 (11): 1359–65. DOI: 10.1161/01.CIR.0000121357.76910.A3
  26. Fisch A.S., Yerges-Armstrong L.M., Backman J.D. et al. Genetic variation in the platelet endothelial aggregation receptor 1 gene results in endothelial dysfunction. PLoS One. 2015; 10 (9). DOI: 10.1371/journal.pone.0138795
  27. Zouein F.A., Booz G.W., Altara R. STAT3 and endothelial cell-cardiomyocyte dialog in cardiac remodeling. Front. Cardiovasc. Med. 2019; 6. DOI: 10.3389/fcvm.2019.00050
  28. Gong L.L., Peng J.H., Han F.F. et al. Association of tissue plasminogen activator and plasminogen activator inhibitor polymorphism with myocardial infarction: A meta-analysis. Thromb. Res. 2012; 130 (3). DOI: 10.1016/j.thromres.2012.06.015
  29. Shi J., Zhi P., Chen J., Wu P., Tan S. Genetic variations in the thrombin-activatable fibrinolysis inhibitor gene and risk of cardiovascular disease: a systematic review and meta-analysis. Thromb. Res. 2014; 134 (3): 610–6. DOI: 10.1016/j.thromres.2014.06.023
  30. Lebedeva A., Maryukhnich E., Grivel J.C., Vasilieva E., Margolis L., Shpektor A. Productive cytomegalovirus infection is associated with impaired endothelial function in ST-elevation myocardial infarction. Am. J. Med. 2020; 133 (1): 133–42. DOI: 10.1016/j.amjmed.2019.06.021

About Authors

  • Anna I. Kalinskaya, Associate Professor, Cand. Med. Sc., ORCID
  • Oleg A. Dukhin, Resident Physician,ORCID
  • Khyadi M. Uzhakhova, Postgraduate, ORCID
  • Aleksander V. Shpektor, Dr. Med. Sc., Professor, Corresponding Member of the Russian Academy of Sciences, Chief of Chair, Head of the University Clinic of Cardiology, ORCID
  • Elena Yu. Vasilieva, Dr. Med. Sc., Professor, Head of Atherothrombosis Laboratory, ORCID

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, Director of Bakoulev National Medical Research Center for Cardiovascular Surgery