Comparative analysis of prothrombotic activity in patients with myocardial infarction with and without obstructive coronary artery disease

Aim. To compare parameters of prothrombotic activity in patients with myocardial infarction (MI) with obstructive (MICAD) and non-obstructive coronary artery disease (MINOCA).

Material and methods. The study included 40 patients with MI, which were divided into experimental (n=19) and control group (n=21). Three patients (15,7%) with acute myocarditis were excluded from the analysis. Hemostasiological and hematological blood tests were studied upon admission, on the 2nd, 4th, 7th days from hospitalization. Blood samples for protein C, antithrombin, von Willebrand factor (VWF), plasminogen, homocysteine were performed on 4th±1 day from hospitalization. To determine the IgG/IgM anticardiolipin (aCL) and anti-beta 2 glycoprotein I (β2-GPI) antibodies in order to diagnose antiphospholipid syndrome (APS), the ORGENTEC Anti- β2-Glycoprotein I IgG/IgM ELISA enzyme immunoassay was used. Blood tests for lupus anticoagulant were performed using an ACL-Top 700 analyzer (Werfen) with HemosIL SynthASil dRVVT screen/dRVVT confirm and with a SCT screen/SCT confirm quartz activator.

Results. According to the data obtained, it was found that patients with MINOCA had a significantly lower level of plasminogen (p=0,007), as well as a higher level of homocysteine (p=0,03). For such indicators as protein C, antithrombin, ejection fraction, differences between the groups were not revealed (p<0,05). At the same time, protein C deficiency was detected in 2 (12,5%) patients with MINOCA and in 1 (5,3%) patient in the control group. Antithrombin deficiency was detected in 2 (12,5%) patients with MINOCA and in 2 (9,5%) patients with MICAD. An increase in the level of ejection fraction was found in 6 (37,5%) patients in the study group and in 7 (33,3%) patients in the control group. There were no differences in levels of lupus anticoagulant, aCL and β2-GPI antibodies (p>0,05). There was a higher platelet count in patients with MINOCA on the 2^nd and 4^th days of acute MI (p=0,46 and p=0,01, respectively). However, the hemoglobin level in patients with MINOCA was significantly lower on admission, 4^th and 7^th day of MI (p=0,02, p=0,03 and p=0,04, respectively).

Conclusion. According to the study results, in patients with MINOCA and MICAD, differences in blood thrombotic activity were revealed. A higher level of homocysteine and a lower level of plasminogen were determined in patients with MINOCA. For such parameters as protein C, antithrombin, VWF, aCL and β2-GPI antibodies, differences between the groups were not determined. According to laboratory data, patients with MINOCA showed higher platelet count, but lower levels of hemoglobin and hematocrit in the early postinfarction period.

1. Spronk HMH, Padro T, Siland JE, et al. Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis. Thromb Haemost. 2018;118(2):229-50. doi:10.1160/TH17-07-0492.

2. Pustjens TFS, Appelman Y, Damman P, et al. Guidelines for the Management of Myocardial infarction/injury With Non-Obstructive Coronary Arteries (MINOCA): A Position Paper From the Dutch ACS Working Group. Neth Heart J. 2020;28(3):116-30. doi:10.1007/s12471-019-01344-6.

3. Momot AP. The problem of thrombophilia in clinical practice. Russian Journal of Children Hematology and Oncology. 2015;2(1):36-48. (In Russ.) doi:10.17650/2311-1267-2015-1-36-48.

4. Prediman K. Shah Thrombogenic risk factors for atherothrombosis Rev. Cardiovasc Med. Winter. 2006;7(1):10-6.

5. Pasupathy S, Air TM, Dreyer RP, et al. Systematic Review of Patients Presenting With Suspected Myocardial Infarction and Nonobstructive Coronary Arteries. Circulation. 2015;131(10):861-70. doi:10.1161/CIRCULATIONAHA.114.011201.

6. Da Costa A, Tardy B, Haouchette K, et al. Long term prognosis of patients with myocardial infarction and normal coronary angiography: impact of inherited coagulation disorders. Thromb Haemost. 2004;91(2):388-93.

7. Fedorova SB, Kulagina IV, Ryabov VV. Hemostatic Gene Polymorphisms in Acute Coronary Syndrome with Nonobstructive Coronary Atherosclerosis. Kardiologiia. 2019;59(10):14-22. (In Russ.)

8. Ryabov VV, Gomboeva SB, Lugacheva YuD, et al. Unfavorable variants of folate metabolism genes in patients with acute coronary syndrome in non-obstructive coronary atherosclerosis. Russian Journal of Cardiology. 2018;23(10):33-42. (In Russ.) doi:10.15829/1560-4071-2018-10-33-42.

9. Nazir S, Tachamo N, Lohani S, et al. Acute myocardial infarction and antiphospholipid antibody syndrome: a systematic review. Coron Artery Dis. 2017;28(4):332-5. doi:10.1097/MCA.0000000000000476.

10. Gandhi H, Ahmed N, Spevack DM. Prevalence of Myocardial Infarction With NonObstructive Coronary Arteries (MINOCA) Amongst Acute Coronary Syndrome in Patients With Antiphospholipid Syndrome. Int J Cardiol Heart Vasc. 2019;22:148-9. doi:10.1016/j. ijcha.2018.12.015.

11. Sharif-Yakan A, Divchev D, Trautwein U, Nienaber ChA. The coronary slow flow phenomena or “cardiac syndrome Y”: Reviews in Vascular Medicine. 2014;2(4):118-22. doi:10.1016/j. rvm.2014.07.001.

12. Boekholdt S, Kramer M. Arterial Thrombosis and the Role of Thrombophilia. Seminars in Thrombosis and Hemostasis. 2007;33(6):588-96. doi:10.1055/s-2007-985755.

13. Celik M, Altintas A, Celik Y, et al. Thrombophilia in young patients with acute myocardial infarction. Saudi Med J. 2008;29(1):48-54.

14. Roldán V, Ordoñez A, Marín F, et al. Antithrombin Cambridge II (A384S) supports a role for antithrombin deficiency in arterial thrombosis. Thromb Haemost. 2009;101(3):483-6.

15. Yang B, Fan S, Zhi X, et al. Prevalence of Hyperhomocysteinemia in China: A Systematic Review and Meta-Analysis. Nutrients. 2015;7:74-90. doi:10.3390/nu7010074.

16. Ma Y, Li L, Geng XB, et al. Correlation Between Hyperhomocysteinemia and Outcomes of Patients With Acute Myocardial Infarction. Am J Ther. 2016;23(6):e1464-e1468. doi:10.1097/MJT.0000000000000130.

17. Huynh DTN, Heo KS. Therapeutic targets for endothelial dysfunction in vascular diseases. Arch Pharm Res. 2019;42(10):848-61. doi:10.1007/s12272-019-01180-7.

18. Fefelova EV, Tereshkov PP, Isakova NV, et al. Some ways of hypercoagulation development in ischemic heart disease patients. ENI Trans-Baikal Medical Bulletin. 2019;2:90-8. (In Russ.)

19. Demirci E, Çelik O, Kalçık M, et al. Evaluation of homocystein and asymmetric dimethyl arginine levels in patients with coronary slow flow phenomenon. Interv Med Appl Sci. 2019;11(2):89-94. doi:10.1556/1646.11.2019.07.

20. Wang X, Zhao J, Zhang Y, et al. Kinetics of plasma von Willebrand factor in acute myocardial infarction patients: a meta-analysis. Oncotarget. 2017;8(52):90371-9. doi:10.18632/oncotarget.20091.

21. Dobrovolsky AB, Titaeva EV. Screening of clotting system disorders by laboratory tests. Russ J Cardiol. 2015;(3):52-7. (In Russ.) doi:10.15829/1560-4071-201503-52-57.

22. Svenungsson E, Antovic A. The antiphospholipid syndrome — often overlooked cause of vascular occlusions? J Intern Med. 2020;287(4):349-72. doi:10.1111/joim.13022.

23. Stepien K, Nowak K, Wypasek E, et al. High prevalence of inherited thrombophilia and antiphospholipid syndrome in myocardial infarction with non-obstructive coronary arteries: Comparison with cryptogenic stroke Comparative Study. Int J Cardiol. 2019;290:1-6. doi:10.1016/j.ijcard.2019.05.037.

24. Szmitko PE, Wang Ch-H, Weise RD, et al. New markers of inflammation and endothelial cell activation: Part I. Circulation. 2003;108(16):1917-23. doi:10.1161/01.CIR.0000089190.95415.9F.

25. Hjort M, Eggers KM, Lindhagen L, et al. Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries. Clin Chem. 2019;65(8):1023-30. doi:10.1373/clinchem.2018.301085.