Analysis of hereditary thrombophilia and antiphospholipid syndrome in patients with acute coronary syndrome based on registry data in the Krasnodar Territory

Objective: to evaluate the prevalence of congenital and acquired thrombophilia in patients with myocardial infarction (MI).

Materials and methods: thrombophilic factors were studied in patients included in the registry of acute coronary syndrome in the Krasnodar Territory. The sample included patients who were admitted for acute myocardial infarction at the Ochapovsky Regional Clinical Hospital, from November 2023 to November 2024, and who meet the universal diagnostic criteria for acute myocardial infarction. Based on the coronary angiography data, two groups were identified: 1 — patients with coronary artery stenosis 150%), lipoprotein (a) (> 30 mg/dl) and homocysteine (≥15 µm) were evaluated.

Results: a comparison was conducted of 100 sequentially enrolled patients with myocardial infarction without obstructive (stenosis 50%) coronary arteries (MIOCA) (the average age is 50.8±12.9 years). The most significant incidence of hereditary thrombophilia was found in the group of patients with MINOCA (21 patients (21%) versus 9 (8.8%) with MIOKA (p=0.0076). In addition, hyperhomocysteinemia, APS, and elevated factor VIII were also more common among MINOCA patients. APS was detected in 13 (13.0%) patients with IBD, mainly in a single-positive form, and prevailed in patients with non-ST segment elevation myocardial infarction (11 patients (11.0%) versus 2 patients (2.0%) with ST segment elevation, p=0.0035). In turn, lipoprotein (a) was more common in patients with MIOKA (32 patients (31.4%) versus 18 patients (18.0%) with MIOKA, p=0.0221.

Conclusions: the prevalence of thrombophilia, including APS, is higher in the group of patients without significant coronary artery damage. The study demonstrates that screening and detection of thrombophilia in patients with MINOCA is of high clinical importance. Based on the data obtained, it can be assumed that the appointment of long-term anticoagulant therapy will have a favorable prognosis in patients with IBD with certain disorders, especially with AFS.

1. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, et al. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017;38(3):143-153. https://doi.org/10.1093/eurheartj/ehw149

2. Gehrie ER, Reynolds HR, Chen AY, Neelon BH, Roe MT, et al. Characterization and outcomes of women and men with non-ST-segment elevation myocardial infarction and nonobstructive coronary artery disease: results from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) quality improvement initiative. Am Heart J. 2009;158(4):688-694. https://doi.org/10.1016/j.ahj.2009.08.004

3. Pasupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation. 2015;131(10):861-870. Erratum in: Circulation. 2015;131(19):e475. https://doi.org/10.1161/CIRCULATIONAHA.114.011201

4. Scalone G, Niccoli G, Crea F. Editor’s Choice- Pathophysiology, diagnosis and management of MINOCA: an update. Eur Heart J Acute Cardiovasc Care. 2019;8(1):54-62. https://doi.org/10.1177/2048872618782414

5. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-177. https://doi.org/10.1093/eurheartj/ehx393

6. Kardasz I, De Caterina R. Myocardial infarction with normal coronary arteries: a conundrum with multiple aetiologies and variable prognosis: an update. J Intern Med. 2007;261(4):330-348. https://doi.org/10.1111/j.1365-2796.2007.01788.x

7. ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to the global disease burden. J Thromb Haemost. 2014;12(10):1580-1590. https://doi.org/10.1111/jth.12698

8. Middeldorp S. Inherited thrombophilia: a double-edged sword. Hematology Am Soc Hematol Educ Program. 2016;2016(1):1-9. https://doi.org/10.1182/asheducation-2016.1.1

9. Prandoni P. Links between arterial and venous disease. J Intern Med. 2007;262(3):341-350. https://doi.org/10.1111/j.1365-2796.2007.01815.x

10. Mega JL, Braunwald E, Wiviott SD, Bassand JP, Bhatt DL, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9-19. https://doi.org/10.1056/NEJMoa1112277

11. Reitsma PH, Rosendaal FR. Past and future of genetic research in thrombosis. J Thromb Haemost. 2007;5 Suppl 1:264-269. https://doi.org/10.1111/j.1538-7836.2007.02502.x

12. Khan S, Dickerman JD. Hereditary thrombophilia. Thromb J. 2006;4:15. https://doi.org/10.1186/1477-9560-4-15

13. Burzotta F, Paciaroni K, De Stefano V, Chiusolo P, Manzoli A, et al. Increased prevalence of the G20210A prothrombin gene variant in acute coronary syndromes without metabolic or acquired risk factors or with limited extent of disease. Eur Heart J. 2002;23(1):26-30. https://doi.org/10.1053/euhj.2001.2685

14. Kruchinova S.V., Kosmacheva E.D., Raff S.A., Tatarintseva Z.G., Porhanov V.A. Results of dynamic follow-up for patients with myocardial infarction without obstructive lesion of coronary arteries: data of the overall register for acute coronary syndrome in Krasnodar region. Innovative Medicine of Kuban. 2019;(2):6-12. (In Russ.) https://doi.org/10.35401/2500-0268-2019-14-2-6-12

15. Wypasek E, Corral J, Alhenc-Gelas M, Sydor W, Iwaniec T, et al. Genetic characterization of antithrombin, protein C, and protein S deficiencies in Polish patients. Pol Arch Intern Med. 2017;127(7-8):512-523. https://doi.org/10.20452/pamw.4045

16. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306. https://doi.org/10.1111/j.1538-7836.2006.01753.x

17. Celińska-Lowenhoff M, Iwaniec T, Padjas A, Musiał J, Undas A. Altered fibrin clot structure/function in patients with antiphospholipid syndrome: association with thrombotic manifestation. Thromb Haemost. 2014;112(2):287-296. https://doi.org/10.1160/TH13-11-0980

18. Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7(10):1737-1740. https://doi.org/10.1111/j.1538-7836.2009.03555.x

19. Rodgers SE, Wong A, Gopal RD, Dale BJ, Duncan EM, McRae SJ. Evaluation of pre-analytical variables in a commercial thrombin generation assay. Thromb Res. 2014;134(1):160-164. https://doi.org/10.1016/j.thromres.2014.04.010

20. Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun. 2000;15(2):145-151. https://doi.org/10.1006/jaut.2000.0409

21. Graziani MS, Zanolla L, Righetti G, Nicoli M, Modena N, et al. Lipoprotein(a) concentrations are increased in patients with myocardial infarction and angiographically normal coronary arteries. Eur J Clin Chem Clin Biochem. 1993;31(3):135-137. PMID: 8490059.

22. Franchini M, Martinelli I, Mannucci PM. Uncertain thrombophilia markers. Thromb Haemost. 2016;115(1):25-30. https://doi.org/10.1160/TH15-06-0478

23. Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296(22):2720-2726. Erratum in: JAMA. 2007;297(9):952. https://doi.org/10.1001/jama.296.22.2720.

24. Bereczky Z, Balogh L, Bagoly Z. Inherited thrombophilia and the risk of myocardial infarction: current evidence and uncertainties. Kardiol Pol. 2019;77(4):419-429. https://doi.org/10.33963/KP.14804

25. Bala MM, Celinska-Lowenhoff M, Szot W, Padjas A, Kaczmarczyk M, et al. Antiplatelet and anticoagulant agents for secondary prevention of stroke and other thromboembolic events in people with antiphospholipid syndrome. Cochrane Database Syst Rev. 2017;10(10):CD012169. Update in: Cochrane Database Syst Rev. 2020;10:CD012169. https://doi.org/10.1002/14651858.CD012169.pub2.

26. Ruiz-Irastorza G, Cuadrado MJ, Ruiz-Arruza I, Brey R, Crowther M, et al. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. 2011;20(2):206-218. https://doi.org/10.1177/0961203310395803

27. Forastiero R. Multiple antiphospholipid antibodies positivity and antiphospholipid syndrome criteria re-evaluation. Lupus. 2014;23(12):1252-1254. https://doi.org/10.1177/0961203314531635