Arterial and venous thrombosis. Is the Virchow’s triad always valid?
https://doi.org/10.24884/1682-6655-2022-21-1-78-86
Abstract
Despite the success of conservative and surgical treatment of vascular diseases, the prevention of arterial and venous thrombosis remains extremely actual. For more than a hundred years, the so-called «Virchow’s triad» has been used to explain the mechanism of thrombosis: 1–slowing of blood flow; 2–hypercoagulation; 3 – damage to the vascular wall. However, the combination of these factors is fully applicable only for venous thrombosis and limited for arterial thrombosis. The generally accepted strategy for the prevention of venous thrombosis is the use of anticoagulants, while for arterial thrombosis – antiaggregants. In recent years the mechanisms of blood clot formation at high blood flow rates in the areas of arterial stenosis, as well as the role of platelets and von Willebrand factor in this process, were investigated. In the presented review, the details of the mechanisms of thrombosis in the arteries are analyzed and the concept of «arterial triad» is introduced. Arterial triad includes: 1 – arterial stenosis (increase in shear rate); 2 – platelets (their activation and interaction with von Willebrand factor); 3 – damage of the vascular wall. The arterial triad describes the mechanisms of thrombosis in the presence of artery stenosis (usually due to atherosclerosis). Understanding similarities and differences between Virchow’s and arterial triads, will allow us to estimate the risk factors in patients with cardiovascular pathology and develop optimal methods of their prevention.
About the Authors
T. D. Vlasov
Pavlov University
Russian Federation
Russian Federation
Vlasov Timur D. – Dr. of Sci. (Med.), professor, head of the Department of Pathophysiology with a course of clinical pathophysiology
6-8, L’va Tolstogo str., Saint Petersburg, 197022
S. M. Yashin
Pavlov University
Russian Federation
Russian Federation
Yashin Sergey M. – Dr. of Sci. (Med.), professor, Head of the department of hospital surgery ¹ 2 with clinics
6-8, L’va Tolstogo str., Saint Petersburg, 197022
References
1. Huang W, Goldberg RJ, Anderson FA et al. Secular trends in occurrence of acute venous thromboembolism: the Worcester VTE study (1985–2009) // Am. J. Med. 2014;(127):829–839.e5.
2. Raskob GE, Angchaisuksiri P, Blanco AN et al. ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease burden // Arterioscler. Thromb. Vasc. Biol. 2014;(34):2363–2371. Doi: 10.1161/ATVBAHA.114.304488.
3. Bagot CN, Arya R. Virchow and his triad: a question of attribution // Brit. J. Haematology. 2008;143(2):180–190. Doi: 10.1111/j.1365-2141.2008.07323.x
4. Lippi G, Favaloro EJ. Venous and Arterial Thromboses: Two Sides of the Same Coin? / Semin // Thromb. Hemost. 2018; 44(03):239–248. Doi: 10.1055/s-0037-1607202.
5. Sevitt S. The structure and growth of valve-pocket thrombi in femoral veins // J. Clin. Pathol. 1974;27(7):517–528. Doi:10.1136/jcp.27.7.517.
6. Jadaon MM. Epidemiology of Prothrombin G20210A Mutation in the Mediterranean Region // Mediterr J Hematol Infect Dis. 2011;3(1):e2011054. Doi: 10.4084/MJHID.2011.054
7. Kujovich JL. Factor V Leiden thrombophilia // Genet. Med. 2011;13(1):1–16. Doi: 10.1097/GIM.0b013e3181faa0f2.
8. Mackman N. New insights into the mechanisms of venous thrombosis // J Clin. Invest. 2012; 122(7):2331–2336. Doi:10.1172/JCI60229.
9. Bovill EG, van der Vliet A. Venous valvular stasis-associated hypoxia and thrombosis: what is the link? // Annu Rev Physiol. 2011;(73):527–545. Doi: 10.1146/annurev-physiol012110-142305.
10. Castro-Ferreira R, Cardoso R, Leite-Moreira A, Mansilha A The Role of Endothelial Dysfunction and Inflammation in Chronic Venous Disease // Ann. Vasc. Surgery. 2018; (46):380–393. Doi: 10.1016/j.avsg.2017.06.131.
11. Janaszak-Jasiecka A, Siekierzycka A, Płoska A et al. Endothelial Dysfunction Driven by Hypoxia – The Influence of Oxygen Deficiency on NO Bioavailability // Biomolecules. 2021;11 (7):982. Doi: 10.3390/biom11070982.
12. Osterud B, Bjorklid E. Tissue factor in blood cells and endothelial cells / /Front Biosci (Elite Ed). 2012;(4):289–299. Doi: 10.2741/376.
13. Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis // BMC Cardiovasc Disord. 2015;(15):130. Doi: 10.1186/s12872-015-0124-z.
14. Poredos P, Jezovnik MK. Endothelial Dysfunction and Venous Thrombosis // Angiology. 2018;69(7):564–567. Doi: 10.1177/0003319717732238.
15. Smeets MWJ, Mourik MJ, Niessen HWM, Hordijk PL. Stasis Promotes Erythrocyte Adhesion to von Willebrand Factor // Arter. Thromb. Vasc. Biol. 2017;37(9):1618–1627. Doi: 10.1161/atvbaha.117.309885
16. Lobastov KV, Dement’eva GI, Laberko LA. Sovremennye predstavleniya ob etiologii i patogeneze venoznogo tromboza: pereosmyslenie triady Virhova // Flebologiya. 2019;13(3):227–235. (In Russ.). Doi: 10.17116/flebo201913031227.
17. Mizuno K, Satomura K, Miyamoto A et al. Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes // N. Engl. J. Med. 1992;326(5):287–291. Doi: 10.1056/NEJM199201303260502.
18. Bennett PC, Silverman SH, Gill PS, Lip GY. Peripheral arterial disease and Virchow’s triad // Thromb. Haemost. 2009;101(6):1032–1040. Doi: 10.1160/TH08-08-0518.
19. Bank I, Libourel EJ, Middeldorp S et al. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancyrelated complications in a family study // Arch Intern Med. 2004;164(17):1932–1937. Doi: 10.1001/archinte.164.17.1932.
20. Sampram ES, Lindblad B. The impact of factor V mutation on the risk for occlusion in patients undergoing peripheral vascular reconstructions // Eur. J. Vasc. Endovasc. Surg. 2001;22 (2):134–138. Doi: 10.1053/ejvs.2001.1420.
21. Kuruvilla A, Norris GM, Manjila S et al. Factor v leiden mutation in reocclusion after intra-arterial thrombolysis // Stroke. 2009;40(2):660–662. Doi: 10.1161/STROKEAHA. 108.522771.
22. Massoudy P, Thielmann M, Müller-Beissenhirtz H et al. Thrombophilia in cardiac surgery-patients with symptomatic factor V Leiden // J. Card. Surg. 2009;24(4):379–382. Doi: 10.1111/j.1540-8191.2008.00761.x.
23. Badimon L, Vilahur G. Thrombosis formation on atherosclerotic lesions and plaque rupture // J. Intern. Med. 2014; 276(6):618–632. Doi: 10.1111/joim.12296.
24. Palasubramaniam J, Wang X, Peter K. Myocardial Infarction-From Atherosclerosis to Thrombosis // Arterioscler Thromb Vasc Biol. 2019;39(8):E176–E185. Doi: 10.1161/ATVBAHA.119.312578.
25. Satoh K, Satoh T, Yaoita N, Shimokawa H. Recent Advances in the Understanding of Thrombosis // Arterioscler. Thromb. Vasc Biol. 2019;39(6):E159–E165. Doi: 10.1161/ ATVBAHA.119.312003.
26. Abdelhalim MA. The effects of size and period of administration of gold nanoparticles on rheological parameters of blood plasma of rats over a wide range of shear rates: in vivo // Lipids Health. Dis. 2011;(10):191. Doi: 10.1186/1476- 511X-10-191.
27. Kroll MH, Hellums JD, McIntire LV et al. Platelets and shear stress // Blood. 1996;88(5): 1525–1541. Doi: 10.1182/ blood.V88.5.1525.1525.
28. Bark DLJr, Ku DN. Wall shear over high degree stenoses pertinent to atherothrombosis // J Biomech. 2010;43(15):2970– 2977. Doi: 10.1016/j.jbiomech.2010.07.011.
29. Foin N, Gutierrez-Chico JL, Nakatani S et al. Incomplete stent apposition causes high shear flow disturbances and delay in neointimal coverage as a function of strut to wall detachment distance // Circulation: Cardiovascular Interventions. 2014;7(2):180–189. Doi: 10.1161/CIRCINTERVENTIONS.113.000931.
30. Stockschlaeder M, Schneppenheim R, Budde U. Update on von Willebrand factor multimers: focus on high-molecularweight multimers and their role in hemostasis // Blood Coagul. Fibrinolysis. 2014;25(3):206–216. Doi: 10.1097/MBC. 0000000000000065.
31. Chen X, Cheng X, Zhang S, Wu D. ADAMTS13: An Emerging Target in Stroke Therapy // Front. Neurol. 2019; (10):772. Doi: 10.3389/fneur.2019.00772.
32. Schneider SW, Nuschele S, Wixforth A et al. Shearinduced unfolding triggers adhesion of von Willebrand factor fibers // Proceedings of the National Academy of Sciences. 2007;104(19):7899–7903. Doi: 10.1073/pnas.0608422104.
33. Xu ER. von Bülow S, Chen PC et al. Structure and dynamics of the platelet integrin-binding C4 domain of von Willebrand factor // Blood. 2019;133(4):366–376. Doi: 10.1182/ blood-2018-04-843615.
34. Wellings PJ, Ku DN. Mechanisms of Platelet Capture Under Very High Shear // Cardiovasc. Engin. Technol. 2012; 3(2):161–170. Doi: 10.1007/s13239-012-0086-6.
35. Shankaran H, Alexandridis P, Neelamegham S. Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension // Blood. 2003;101(7):2637–2645. Doi: 10.1182/ blood-2002-05-1550.
36. Zhang C, Kelkar A, Neelamegham S. von Willebrand factor self-association is regulated by the shear-dependent unfolding of the A2 domain // Blood Adv. 2019;3(7):957–968. Doi: 10.1182/bloodadvances.2018030122/
37. Ruggeri ZM, Orje JN, Habermann R et al. Activationindependent platelet adhesion and aggregation under elevated shear stress // Blood. 2006;108(6):1903–1910. Doi: 10.1182/ blood-2006-04-011551.
38. Ku DN. Blood flow in arteries // Annual Review of Fluid Mechanics. 1997;(29):399–434. Doi: 10.1146/annurev.fluid.29.1.399
39. Chatzizisis YS, Coskun AU, Jonas M et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior // J. Am. Coll. Cardiol. 2007;49(25):2379– 2393. Doi: 10.1016/j.jacc.2007.02.059.
40. Yamamoto E, Siasos G, Zaromytidou M et al. Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study // Circ. Cardiovasc. Interv. 2017;10(8): e005455. Doi: 10.1161/CIRCINTERVENTIONS.117.005455.
41. Bryan MT, Duckles H, Feng S et al. Mechanoresponsive networks controlling vascular inflammation // Arterioscler. Thromb. Vasc Biol. 2014;34(10):2199–2205. Doi: 10.1161/ ATVBAHA.114.303424.
42. Kim D, Bresette C, Liu Z. Ku D.N. Occlusive thrombosis in arteries // APL Bioeng. 2019;3 (4):041502. Doi: 10.1063/1.5115554.
43. Warny M, Helby J, Birgens HS et al. Arterial and venous thrombosis by high platelet count and high hematocrit: 108 521 individuals from the Copenhagen General Population Study // J. Thromb. Haemost. 2019;17(11):1898–1911. Doi: 10.1111/jth.14574.
44. Juif PE, Boehler M, Dobrow M et al. Clinical Pharmacology of the Reversible and Potent P2Y12 Receptor Antagonist ACT-246475 After Single Subcutaneous Administration in Healthy Male Subjects // J. Clin. Pharmacol. 2019;59(1):123– 130. Doi: 10.1002/jcph.1296.
45. Sinnaeve P, Fahrni G, Schelfaut D, Spirito A, Mueller C et al. Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction // J Am Coll Cardiol 2020;(75):2588–2597
46. Bowry AD, Brookhart MA, Choudhry NK. Meta-analysis of the efficacy and safety of clopidogrel plus aspirin as compared to antiplatelet monotherapy for the prevention of vascular events // Am. J. Cardiol. 2008;(101):960–966. Doi: 10.1016/j.amjcard.2007.11.057
47. Rothberg MB, Celestin C, Fiore LD et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit // Ann Intern Med. 2005;143(4):241–250. Doi: 10.7326/0003- 4819-143-4-200508160-00005.
48. Dans AL, Connolly SJ, Wallentin L et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the randomized evaluation of long-term anticoagulation therapy (RE-LY) trial // Circulation. 2013;(127):634–640. Doi: 10.1161/CIRCULATIONAHA.112.115386.
49. Shah R, Hellkamp A, Lokhnygina Y. Becker et al. ROCKET AF Steering Committee Investigators. Use of concomitant aspirin in patients with atrial fibrillation: findings from the ROCKET AF trial // Am. Heart. J. 2016;(179):77–86. Doi: 10.1016/j.ahj.2016.05.019.
50. Xu H, Ruff CT, Giugliano RP et al. Concomitant use of single antiplatelet therapy with edoxaban or warfarin in patients with atrial fibrillation: analysis from the ENGAGE AF-TIMI 48 trial // J. Am. Heart Assoc. 2016;5(2):E002587. Doi: 10.1161/JAHA.115.002587.
51. Ruff CT, Giugliano RP, Braunwald E et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials // Lancet. 2014;383(9921):955–962. Doi: 10.1016/S0140-6736(13)62343-0.
52. Weitz JI, Chan NC. Advances in Antithrombotic Therapy // Arterioscler Thromb Vasc Biol. 2019;(39):7–12. Doi: 10.1161/ATVBAHA.118.310960.
Review
For citations:
Vlasov T.D., Yashin S.M. Arterial and venous thrombosis. Is the Virchow’s triad always valid? Regional blood circulation and microcirculation. 2022;21(1):78-86. (In Russ.) https://doi.org/10.24884/1682-6655-2022-21-1-78-86
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