Register
Forgot your password?

Diagnosis of the increased thrombotic risk in patients with chronic coronary syndrome after percutaneous coronary intervention: focus on the immune and fibrinolytic systems

Authors: Anisimova A.S.2, Rusakovich G.I.2, Maryukhnich E.V.1 2, Ivanova O.I., 1 2 Kordzaya E.L.2, Elizarova A.K.2, Kononikhin A.S.4, Bugrova A.E.3 4, Zakharova N.V.3 4, Nikolaev E.N.4, Vasilieva E.Yu.1 2

Company: 1 Russian University of Medicine, Moscow, Russian Federation
2 Davydovskiy City Clinical Hospital, Moscow, Russian Federation
3 Emanuel Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russian Federation
4 Skolkovo Institute of Science and Technology, Moscow, Russian Federation

For correspondence:  Sign in or register.

Type:  Original articles


DOI: https://doi.org/10.24022/1997-3187-2026-20-1-115-127

For citation: Anisimova A.S., Rusakovich G.I., Maryukhnich E.V., Ivanova O.I., Kordzaya E.L., Elizarova A.K., Kononikhin A.S., Bugrova A.E., Zakharova N.V., Nikolaev E.N., Vasilieva E.Yu. Diagnosis of the increased thrombotic risk in patients with chronic coronary syndrome after percutaneous coronary intervention: focus on the immune and fibrinolytic systems. Creative Cardiology. 2026; 20 (1): 115–127 (in Russ.). DOI: 10.24022/1997-3187-2026-20-1-115-127

Received / Accepted:  12.01.2026 / 03.03.2026

Keywords: chronic coronary syndrome antiplatelet therapy ischemic events immunothrombosis proteomic analysis



Subscribe 🔒

 

Abstract

Objective. To identify factors associated with increased risk of thrombotic complications in patients with chronic coronary syndrome (CCS) after percutaneous coronary intervention (PCI).

Material and methods. We enrolled 72 CCS patients after PCI receiving dual antiplatelet therapy (DAPT). All the patients underwent platelet aggregation assessment by impedance aggregometry and plasma proteomic profiling at admission and on 3–5 days after DAPT initiation. At 12 months, the incidence of thrombotic events was assessed and patients were classified into two groups: Group 1 – patients without thrombotic complications, Group 2 – patients with thrombotic complications.

Results. In both groups, aggregometry parameters were within target ranges under DAPT. Mass-spectrometric analysis revealed 10 differentially represented proteins between groups, five of which are involved in immune system regulation. Univariate logistic regression identified the strongest predictors of thrombotic events: circulating monocyte count (log ORstd = 2,109; 95% CI 2,724–1196,471; p = 0,007) and concentrations of several plasma proteins – inter-α-trypsin inhibitor heavy chain H4 (log ORstd = 1,112; 95% CI 0,245–2,167; p = 0,013), gelsolin (log ORstd = 1,064; 95% CI 0,240–2,097; p= 0,011), C1-esterase inhibitor (log ORstd = –1,776; 95% CI –3,861…–0,217; p = 0,024),

and phospholipid transfer protein (log ORstd = –2,145; 95% CI –4,503…–0,482; p = 0,008).

Conclusion. We identified factors whose levels are associated with increased risk of thrombotic complications in CCS patients after PCI. Thrombotic complications in CCS patients may be driven by immune system activation and an imbalance in the fibrinolytic system. Further research is required before clinical implementation of these factors as biomarkers.

References

  1. Mehran R., Baber U., Steg P.G. et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2-year results from a prospective observational study. Lancet. 2013; 382: 1714–1722. DOI: 10.1016/S0140-6736(13)61720-1
  2. Barbarash O.L., Karpov Yu.A., Panov A.V. et al. 2024 Clinical practice guidelines for stable coronary artery disease. Russian Journal of Cardiology. 2024; 29: 6110 (in Russ.). DOI: 10.15829/1560-4071-2024-6110
  3. Vrints C., Andreotti F., Koskinas K.C. et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur. Heart J. 2024; 45: 3415–3537. DOI: 10.1093/eurheartj/ehae177
  4. Collet J.-P., Cuisset T., Rangé G. et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N. Engl. J. Med. 2012; 367: 2100–2109. DOI: 10.1056/NEJMoa1209979
  5. Cayla G., Cuisset T., Silvain J. et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016; 388: 2015–2022. DOI: 10.1016/S0140-6736(16)31323-X
  6. Ridker P.M., Everett B.M., Thuren T. et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N. Engl. J. Med. 2017; 377: 1119–1131. DOI: 10.1056/NEJMoa1707914
  7. Dregoesc M.I., Țigu A.B., Bekkering S. et al. Intermediate monocytes are associated with the first major adverse cardiovascular event in patients with stable coronary artery disease. Int. J. Cardiol. 2024; 400: 131780. DOI: 10.1016/j.ijcard.2024.131780
  8. Halimeh S., De Angelis G., Sander A. et al. Multiplate® whole blood impedance point-of-care aggregometry: preliminary reference values in healthy infants, children and adolescents. Klin. Padiatr. 2010; 222: 158–163. DOI: 10.1055/s-0030-1249081
  9. Kononikhin A.S., Starodubtseva N.L., Brzhozovskiy A.G. et al. Absolute quantitative targeted monitoring of potential plasma protein biomarkers: a pilot study on healthy individuals. Biomedicines. 2024; 12 (10): 2403. DOI: 10.3390/biomedicines12102403
  10. Angiolillo D.J., Galli M., Alexopoulos D. et al. International Consensus Statement on platelet function and genetic testing in percutaneous coronary intervention. JACC Cardiovasc. Interv. 2024; 17: 2639–2663. DOI: 10.1016/j.jcin.2024.08.027
  11. Mazhar F., Faucon A.-L., Fu E.L. et al. Systemic inflammation and health outcomes in patients receiving treatment for atherosclerotic cardiovascular disease. Eur. Heart J. 2024; 45 (44): 4719–4730. DOI: 10.1093/eurheartj/ehae557
  12. Piñeiro M., Alava M.A., González-Ramón N. et al. ITIH4 serum concentration increases during acute-phase processes in human patients and is up-regulated by interleukin-6 in hepatocarcinoma HepG2 cells. Biochem. Biophys. Res. Commun. 1999; 263: 224–229. DOI: 10.1006/bbrc.1999.1349
  13. Zhao M., Yoneda M., Ohashi Y. et al. Evidence for the covalent binding of SHAP, heavy chains of inter-α-trypsin inhibitor, to hyaluronan. J. Biol. Chem. 1995; 270: 26657–26663. DOI: 10.1074/jbc.270.44.26657
  14. Pihl R., Jensen R.K., Poulsen E.C. et al. ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism. Sci. Adv. 2021; 7: eba7381. DOI: 10.1126/sciadv.aba7381
  15. Osada A., Matsumoto I., Mikami N. et al. Citrullinated interalpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in neutrophil migration. Clin. Exp. Immunol. 2021; 203: 385–399. DOI: 10.1111/cei.13556
  16. Zhuo L., Kimata K. Structure and function of inter-α-trypsin inhibitor heavy chains. Connect. Tissue Res. 2008; 49: 311–320. DOI: 10.1080/03008200802325458
  17. Davis A.E., Mejia P., Lu F. Biological activities of C1 inhibitor. Mol. Immunol. 2008; 45: 4057–4063. DOI: 10.1016/j.molimm.2008.06.028
  18. Kajdácsi E., Jandrasics Z., Veszeli N. et al. Patterns of C1-inhibitor/plasma serine protease complexes in healthy humans and in hereditary angioedema patients. Front. Immunol. 2020; 11: 794. DOI: 10.3389/fimmu.2020.00794
  19. Amara U., Flierl M.A., Rittirsch D. et al. Molecular intercommunication between the complement and coagulation systems. J. Immunol. 2010; 185: 5628–5636. DOI: 10.4049/jimmunol.0903678
  20. Foley J.H., Walton B.L., Aleman M.M. et al. Complement activation in arterial and venous thrombosis is mediated by plasmin. EBioMedicine. 2016; 5: 175–182. DOI: 10.1016/j.ebiom.2016.02.011
  21. Redecha P., Tilley R., Tencati M. et al. Tissue factor: a link between C5a and neutrophil activation in antiphospholipid antibody-induced fetal injury. Blood. 2007; 110: 2423–2431. DOI: 10.1182/blood-2007-01-070631
  22. Wilhelm C.R., Ristich J., Kormos R.L., Wagner W.R. Monocyte tissue factor expression and ongoing complement generation in ventricular assist device patients. Ann. Thorac. Surg. 1998; 65: 1071–1076. DOI: 10.1016/S0003-4975(98)00111-8
  23. Nan J., Meng S., Hu H. et al. The predictive value of monocyte count to high-density lipoprotein cholesterol ratio in restenosis after drug-eluting stent implantation. Int. J. Gen. Med. 2020; 13: 1255–1263. DOI: 10.2147/IJGM.S275202
  24. Leatham E.W., Bath P.M., Tooze J.A., Camm A.J. Increased monocyte tissue factor expression in coronary disease. Heart. 1995; 73: 10–13. DOI: 10.1136/hrt.73.1.10
  25. Allen N., Barrett T.J., Guo Y. et al. Circulating monocyte-platelet aggregates are a robust marker of platelet activity in cardiovascular disease. Atherosclerosis. 2019; 282: 11–18. DOI: 10.1016/j.atherosclerosis.2018.12.029
  26. Furman M.I., Benoit S.E., Barnard M.R. et al. Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J. Am. Coll. Cardiol. 1998; 31: 352–358. DOI: 10.1016/S0735-1097(97)00510-X
  27. Siller-Matula J.M., Christ G., Lang I.M. et al. Multiple electrode aggregometry predicts stent thrombosis better than the vasodilator-stimulated phosphoprotein phosphorylation assay. J. Thromb. Haemost. 2010; 8: 351–359. DOI: 10.1111/j.1538-7836.2009.03699.x
  28. Gjermeni D., Anfang V., Vetter H. et al. Low on-clopidogrel ADP- and TRAP-6-induced platelet aggregation in patients with atrial fibrillation undergoing percutaneous coronary intervention: an observational pilot study. J. Thromb. Thrombolysis. 2024; 57: 361–369. DOI: 10.1007/s11239-023-02937-0
  29. Bournazos S., Rennie J., Hart S.P. et al. Monocyte functional responsiveness after PSGL-1-mediated platelet adhesion is dependent on platelet activation status. Arterioscler. Thromb. Vasc. Biol. 2008; 28: 1491–1498. DOI: 10.1161/ATVBAHA.108.167601
  30. Jiang X.-C., Jin W., Hussain M.M. The impact of phospholipid transfer protein (PLTP) on lipoprotein metabolism. Nutr. Metab. (Lond.). 2012; 9 (1): 75. DOI: 10.1186/1743-7075-9-75
  31. Robciuc M.R., Metso J., Sima A. et al. Human apoA-I increases macrophage foam cell-derived PLTP activity without affecting the PLTP mass. Lipids Health Dis. 2010; 9: 59. DOI: 10.1186/1476-511X-9-59
  32. Vuletic S., Dong W., Wolfbauer G. et al. PLTP regulates STAT3 and NF-κB in differentiated THP-1 cells and human monocyte-derived macrophages. Biochim. Biophys. Acta Mol. Cell Res. 2011; 1813: 1917–1924. DOI: 10.1016/j.bbamcr.2011.06.013
  33. Ullo M.F., D’Amico A.E., Lavenus S.B., Logue J.S. The amoeboid migration of monocytes in confining channels requires the local remodeling of the cortical actin cytoskeleton by cofilin-1. Sci. Rep. 2024; 14: 10241. DOI: 10.1038/s41598-024-60971-1

About Authors

  • Aleksandra S. Anisimova, Cardiologist; ORCID
  • Georgiy I. Rusakovich, Biostatistician; ORCID
  • Elena V. Maryukhnich, Junior Researcher 1, 2; ORCID
  • Oksana I. Ivanova, Researcher 1, Junior Researcher 2; ORCID
  • Elena L. Kordzaya, Cardiologist; ORCID
  • Antonina K. Elizarova, Cardiologist; ORCID
  • Aleksey S. Kononikhin, Senior Researcher; ORCID
  • Anna E. Bugrova, Senior Researcher 3, 4; ORCID
  • Natalya V. Zakharova, Senior Researcher 3, 4; ORCID
  • Evgeniy N. Nikolaev, Dr. Phys.-Math. Sci., Professor, Corresponding Member of Russian Academy of Sciences, Director of Project Center of Omics Technologies and Advanced Mass Spectrometry; ORCID
  • Elena Yu. Vasilieva, Dr. Med. Sci., Professor of Cardiology Chair, Head of Laboratory of Atherothrombosis 1, president 2; ORCID

Chief Editor

Elena Z. Golukhova, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, Director of Bakoulev National Medical Research Center for Cardiovascular Surgery


Sort by