STUDY OF THE GENETIC ASPECTS OF THE RISK OF SHUNT THROMBOSIS AFTER OPERATIONS IN THE LOWER LIMBS ARTERIES
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Keywords

peripheral artery disease (PAD), critical limb ischemia (CLI), thrombophilia mutations, thrombosis after peripheral arterial bypass

How to Cite

R. V. Sabadosh, V. A. Reshetylo, N. M. Rizyuk, & A. V. Reshetylo. (2019). STUDY OF THE GENETIC ASPECTS OF THE RISK OF SHUNT THROMBOSIS AFTER OPERATIONS IN THE LOWER LIMBS ARTERIES. Eastern Ukrainian Medical Journal, 7(3), 233-245. Retrieved from http://eumj.med.sumdu.edu.ua/index.php/journal/article/view/40

Abstract

Introduction. Critical limb ischemia is a serious threat, and even after surgery for revascularization, only 45% of those operated on retain both extremities within 1 year. During this time, unfortunately, in 30% of cases, the affected limbs are amputated, and the remaining 25% of critical ischemia cases result in death.

Purpose. In order to improve the treatment outcomes of patients with peripheral arterial disease (PAD), the relationship between hemocoagulation-related gene polymorphism and the risk of shunt thrombosis after reconstructive arterial disease has been studied.

Materials and Methods. The study included 40 patients who had previously undergone open reconstructive surgery for peripheral arterial disease, who were divided into two groups. The main criterion for inclusion of the patient in the main group was thrombosis of the shunt at any time after reconstructive surgery, and in the comparison group ­– the absence of thrombosis after peripheral arterial bypass at least 1 year after reconstructive surgery. All patients with polymerase chain reaction were analyzed for the presence of the following hereditary thrombophilia: Leiden factor G1691A, prothrombin G20210A, FGB G (-455) A, ITGA2 C807T, ITGB3 T1565C, PAI-1 5G (-675) 4G and MTHFR.

Discussion. The study found a relationship between FGB G (-455) A, ITGA2 C807T and ITGB3 T1565C gene mutations and thrombosis after peripheral arterial bypass. It has been statistically proven that when there is at least one of the thrombophilia such as FGB G (-455) A, ITGA2 C807T and ITGB3 T1565C present in a patient with peripheral arterial disease, the risk of shunt thrombosis will increase in the future.

A prospective direction for further research is the study of the question of how differentiated additional prevention of thrombosis of arterial shunts in patients with PLEAD depending on the detected hereditary thrombophilia will affect the frequency of thrombosis of these shunts. The study found that in patients with peripheral arterial disease who are planning to undergo surgery on peripheral arteries, it is advisable to study the presence or absence of thrombophilia bypass as FGB G (-455) A, ITGA2 C807T and ITGB3 T1565C. If these patients have at least one of these thrombophilia, the risk of bypass thrombosis in them is statistically significant in the future.

A promising direction for further research may be to investigate how differentiated additional prevention of arterial bypass thrombosis in patients with PAD, depending on the hereditary thrombophilia detected, will affect the frequency of thrombosis of these pass and bypass.

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References

1. Emile R. Mohler, Michael R. Jaff. [Peripheral Artery Disease]. John Wiley & Sons. 2017; 10(2), 1118776097, 9781118776094. 208 p.
2. Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. [Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis]. Lancet. 2013;382:1329–40.
3. Sigvant B, Wiberg-Hedman K, Bergqvist D, Rolandsson O, Andersson B, Persson E, Wahlberg E. [A population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex differences]. J. Vasc. Surg. 2007;45:1185–1191.
4. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FGR. [Inter-society consensus for the management of peripheral arterial disease (TASC II)]. Journal of vascular surgery. 2007;45(1):S5-S67.
5. De Moerloose Philippe, Boehlenn Françoise. Inherited thrombophilia in arterial disease: a selective review. In: Seminars in hematology. WB Saunders. 2007; pp. 106-113.
6. Robert B, Rutherford J, Dennis Baker, Calvin Ernst K, Wayne Johnston, John M Porter, Sam Ahn, Darrell N Jones. [Recommended standards for reports dealing with lower extremity ischemia: Revised version]. J. Vasc. Surg. 1997;26:517-38.
7. Joseph L Mills, Sr Michael S Conte, David G Armstrong, Frank B Pomposelli, Andres Schanzer, Anton N Sidawy, George Andros. [The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and foot Infection (WIfI)]. J. Vasc. Surg. 2014;59:220-34.
8. R Development Core Team. R. A language and environment for statistical computing. R Foundation for Statistical Computing. Retrieved from: http://www.R-project.org/
9. Richa Handa, Sanjiv Sharma. CA Vascular Graft Failure of Leg Arterial bypasses - a Review. Journal of Hypertension and Cardiology. 2014;1(3):17-21. doi: 10.14302 issn.2329-9487, jhc-14-404
10. Van Cott EM, Khor B, Zehnder JL. Factor V Leiden. American Journal of Hematology. 2015;91(1):46–49. doi: 10.1002/ajh.24222
11. Poort, Swibertus R., et al. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996;88(10): 3698-3703.
12. Ye Z, Liu EH, Higgins JP, Keavney BD, Lowe GD, Collins R, et al. [Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66,155 cases and 91,307 controls]. Lancet. 2006;367(9511):651–8.
13. Laki K, Gladner JA. [Chemistry and Physiology of the Fibrinogen-Fibrin Transition].
1. Physiological Reviews. 1964;44(2):127–160. doi: 10.1152/physrev.1964.44.2.127
14. Lee SH, Kim MK, Park MS, Choi SM, Kim JT, Kim BC, Cho KH. [beta-Fibrinogen Gene -455 G/A Polymorphism in Korean Ischemic Stroke Patients]. J. Clin. Neurol. 2008;Mar;4(1):17-22. doi: 10.3988/jcn.2008.4.1.17
15. Alan D. Platelets. Third Edition [3 ed.]. Academic Press, 2013. 1398 p.
16. Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. [Hereditary variation in platelet integrin alpha 2 beta 1 density is associated with two silent polymorphisms in the alpha 2 gene coding sequence]. Blood. 1997;89:1939–1943.
17. Kunicki TJ. [The Influence of Platelet Collagen Receptor Polymorphisms in Hemostasis and Thrombotic Disease]. Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22(1):14-20.
18. Guangliang Wu, Yujing Xi, Li Yao, Li Su,Yan Yan, Minzhi Li, Lian Gu. [Genetic polymorphism of ITGA2 C807T can increase the risk of ischemic stroke]. International Journal of Neuroscience. 2014;124(11):841-851.
19. Bennett JS. [Structure and function of the platelet integrin alpha II bbeta 3]. J Clin Investig. 2005;115(12):3363–9.
20. Galasso G, Santulli G, Piscione F, De Rosa R, Trimarco V, Piccolo R, Chiariello M. [The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events]. BMC Cardiovascular Disorders. 2010;10(1). doi: 10.1186/1471-2261-10-41
21. Martinelli I, Bucciarelli P, Mannucci PM. [Thrombotic risk factors: basic pathophysiology]. Crit Care Med. 2010;38(2):3–9.
22. Tsantes, Argirios E, et al. [The effect of the plasminogen activator inhibitor-1 4G/5G polymorphism on the thrombotic risk]. Thrombosis research. 2008;122(6):736-742.
23. Bowen Derrick John, Bowley S, John M, Collins PW. [Factor V Leiden (G1691A), the Prothrombin 3’-Untranslated Region Variant (G20210A) and Thermolabile Methylenetetrahydrofolate Reductase (C677T): A Single Genetic Test Genotypes all Three Loci–Determination of Frequencies in the S. Wales Population of the UK]. Thromb Haemost. 1998;79(5):949-54.
24. Zivelin Ariella, Rosenberg N, Faier S, Kornbrot N, Peretz H, Mannhalter C, Horellou MH, Seligsohn U. [A single genetic origin for the common prothrombotic G20210A polymorphism in the prothrombin gene]. Blood. 1998;92(4):1119-1124.; Thrombosis and haemostasis. 1998;79(05):949-954.
25. Iso Hiroyasu et al. [Polymorphisms of the beta fibrinogen gene and plasma fibrinogen concentration in Caucasian and Japanese population samples]. Thrombosis and haemostasis. 1995;73(1):106-111.
26. Tsantes AE, Nikolopoulos GK, Bagos PG, Vaiopoulos G, Travlou A. [Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: A meta-analysis]. International Journal of Cardiology. 2007;118(2):189–196. doi: 10.1016/j.ijcard.2006.06.047
27. Shan Wang-Gohrke, Jenny Chang-Claude. [Integrin β3 Leu33Pro polymorphism and breast cancer risk: a population-based case-control study in Germany]. Breast cancer research and treatment. 2004;88(3):231-237.
28. Luhm R, Pearson S, Endean D, Friedman K, Montgomer R, Hessner M. [Prevalence of Prothrombin G20210A, Factor V G1691A (Leiden), and Methylenetetrahydrofolate Reductase (MTHFR) C677T in Seven Different Populations Determined by Multiplex Allele-specific PCR]. Thrombosis and Haemostasis. 1999;81(5):733–738. doi: 10.1055/s-0037-1614563
29. Naran NH, Chetty N, Crowther NJ. [The influence of metabolic syndrome components on plasma PAI-1 concentrations is modified by the PAI-1 4G/5G genotype and ethnicity]. Atherosclerosis. 2008;196(1):155–163. doi: 10.1016/j.atherosclerosis.2007.03.024