Preview

Ateroscleroz

Advanced search

ASPIRIN RESISTANCE AS A RISK MARKER FOR VENOUS THROMBOEMBOLIC COMPLICATIONS

https://doi.org/10.15372/ATER20180405

Abstract

The possible mechanisms for the development of aspirin resistance, platelet involvement in thrombus formation, inflammation and atherogenesisare presented. The presence of associations between aspirin resistance and the risk of thrombotic complications in people not using aspirin and the possibility of using aspirin resistance to assess the individual risk of thromboembolic complications in 492 patients (mean age 56.2 ± 0.9 years) with arterial hypertension I - Stage II and without ithas been researched. The parameters of platelet aggregation were studied in subgroups of patients different in the risk of developing venous thrombo-embolic complications by reaction to the cyclooxygenase blocker. It has been revealed that the conducted antiplatelet therapy is effective in 50-60 % of persons with cardiovascular diseases; ~ 40 % of patients show signs of relative resistance to antiplatelet agents. Resistance to therapeutic doses of antiplatelet agents is multifactorial, however, the presence of a shunt between thromboxane synthetase and lipoxygenase plays a role in it. It is likely that the influence of inflammation on the development of aspirin resistance through an increase in the synthesis of 12-NETU, thromboxane and leukotrienes. Aspirin resistance is a risk factor for the development of venous thrombotic complications, regardless of the use of antiaggregant therapy. It was established that the most accurate prediction of the result according to the severity of hemorheological disorders (distinguishing between moderate and severe disorders from the lungs) is provided by such indicators of platelet aggregation as the coefficient K ((ADF5 % - ADP 5 % + Asp) - 100 / ADF 5 %) (AUC 0.995) and ADP 5 % (AUC 0.713). Changes in platelet aggregation in response to aspirin in an in vitro test can be used to identify individuals with a high risk of thrombotic complications, and to assess individual risk (specificity 92.9-98.2 %, sensitivity 83.7-93 %).

About the Authors

M. V. Kruchinina
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS; Novosibirsk State Medical University of Minzdrav of Russia
Russian Federation


A. A. Gromov
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS
Russian Federation


A. V. Rabko
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS
Russian Federation


P. A. Abdullaeva
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS
Russian Federation


V. A. Baum
Institute of Internal and Preventive Medicine - Branch of Federal Research Institute of Cytology and Genetics of SB RAS
Russian Federation


V. M. Generalov
Federal Budgetary Research Institution «State Research Center of Virology and Biotechnology «Vector», Federal Service for Surveillance on Consumer Rights Protection and Human Well-being
Russian Federation


K. V. Generalov
Federal Budgetary Research Institution «State Research Center of Virology and Biotechnology «Vector», Federal Service for Surveillance on Consumer Rights Protection and Human Well-being
Russian Federation


V. N. Kruchinin
Rzhanov Institute of Semiconductor Physics of SB RAS
Russian Federation


S. V. Rykhlitskiy
Rzhanov Institute of Semiconductor Physics of SB RAS
Russian Federation


G. V. Shuvalov
Siberian State Order of the Red Banner of Labor Institute of Metrology
Russian Federation


References

1. Rothwell P.M., Cook N.R., Gaziano J.M., Price J.F., Belch J.F.F., Roncaglioni M.C., Morimoto T., Mehta Z., Rothwell P.M., Cook N.R., Gaziano J.M. et al. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials // Lancet. 2018. Vol. 392. P. 387-399. DOI: 10.1016/S0140-6736(18)31133-4.

2. Li L., Geraghty O.C., Mehta Z., Rothwell P.M. On behalf of the Oxford Vascular Study Age-Specific Risks, Severity, Time Course, and Outcome of Bleeding on Long-Term Antiplatelet Treatment After Vascular Events: A Population-Based Cohort Study // Lancet. 2017. Vol. 390. P. 490-499. DOI: org/10.1016/S0140-6718(18)31125-2.

3. Schmaier A.A., Bhatt D.L. Are Patients Getting Their Aspirin’s Worth in Ischemic Stroke? // J. Am. Heart Assoc. 2018. Vol. 7, N 11. P. e009564(12). DOI: 10.1161/JAHA.118.009564.

4. Lepropre S., Kautbally S., Octave M., Ginion A., Onselaer M.-B., Steinberg G.R., Kemp B.E., Hego A., Wéra O., Brouns S., Swieringa F., Giera M., Darley-Usmar V.M., Ambroise J., Guigas B., Heemskerk J., Bertrand L., Oury S., Beauloye C., Horman S. AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation // Blood. 2018. Vol. 132, N 11. P. 1180-1192. DOI: https://doi.org/10.1182/blood-2018-02-831503.

5. Yang M., Cooley B.C., Li W., Chen Y., Vasquez-Vivar J., Scoggins N.O., Cameron S.J., Morrell C.N., Silverstein R.L. Platelet CD36 promotes thrombosis by activating redox sensor ERK5 in hyperlipidemic conditions // Blood. 2017. Vol. 129, N 21. P. 2917-2927. DOI: 10.1182/blood-2016-11-750133.

6. Duchez A.C., Boudreau L.H., Naika G.S., Bollinger J., Belleannée C., Cloutier N., Laffont B., Mendoza-Villarroel R.E., Lévesque T., Rollet-Labelle E., Rousseau M., Allaeys I., Tremblay J.J., Poubelle P.E., Lambeau G., Pouliot M., Provost P., Soulet D., Gelb M.H., Boilard E. Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A2-IIA // Proc. Natl. Acad. Sci. U.S.A. 2015. Vol. 112, N 27. P. E3564-E3573. DOI: 10.1073/pnas.1507905112.

7. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients // BMJ. 2002. Vol. 324. P. 71-86. DOI: org/10.1136/bmj.324.7329.71.

8. Guirguis-Blake J.M., Evans C.V., Senger C.A., O’Connor E.A., Whitlock E.P. Aspirin for theprimary prevention of cardiovascular events: asystematic evidence review for the US Preventive Services Task Force // Ann. Intern. Med. 2016. Vol. 164, N 12. P. 804-813. DOI: 10.7326/M15-2113.

9. Antithrombotic Trialists’ (ATT) Collaboration, Baigent C., Blackwell L., Collins R., Emberson J., Godwin J., Peto R., Buring J., Hennekens C., Kearney P., Meade T., Patrono C., Roncaglioni M.C., Zanchetti A. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials // Lancet. 2009. Vol. 373. P. 1849-1660. DOI: 10.1016/S0140-6736(09) 60503-1.

10. McNeil J.J., Wolfe R., Woods R.L., Tonkin A.M., Donnan G.A., Nelson M.R., Reid C.M., Lockery J.E., Kirpach D., Storey E., Shah R.C., Williamson J.D., et al. For the ASPREE Investigator Group.Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly // New Engl. J. Med. 2018. http://dx.doi.org/10.1056/NEJMoa1805819.

11. Gaziano J.M., Brotons C., Coppolecchia R., Cricelli C., Darius H., Gorelick P.B., Howard G., Pearson T.A., Rothwell P.M., Ruilope L.M., Tendera M., Tognoni G. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial // Lancet. 2018. http://dx.doi.org/10.1016/S0140-6736(18)31924-X.

12. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2 // Lancet. 1988. Vol. 332. P. 349-360. DOI: org/10.1016/S0140-6736(88)92833-4.

13. Hennekens С.Н., Sacks F.M., Tonkin A., Jukema J.W., Byington R.P., Pitt B., Berry D.A., Berry S.M., Ford N.F., Walker A.J., Natarajan K., Sheng-Lin C., Fiedorek F.T., Belder R.Additive benefits of prevastin and aspirin to decrease risk of cardiovascular disease: randomized and observational comparisons of secondary prevention trials and their meta-analyses // Arch. Int. Med. 2004. Vol. 164, N 1. P. 40-44. DOI: 10.1001/archinte.164.1.40.

14. Vernstrшm L., Funck K.L., Grove E.L., Laugesen E., Baier J.M., Hvas A.M., Poulsen P. L. Antiplatelet effect of aspirin during 24 h in patients with type 2 diabetes without cardiovascular disease // Thromb. Res. 2018. Vol. 161. P. 1-6. DOI: 10.1016/j.thromres. 2017.11.013.

15. Motovska Z., Bhatt D.L. 12 months of DAPT after acute coronary syndrome still beats 6 months // Lancet. 2018. Vol. 391. P. 1240-1242. DOI: 10.1016/S0140-6736(18)30612-3.

16. Gremmel T., Michelson A.D., Frelinger A.L., Bhatt D.L. Novel aspects of antiplatelet therapy in cardiovascular disease // Res. Pract. Thromb. Haemost. 2018. Vol. 2, N 3. P. 439-449. DOI: 10.1002/rth2.12115.

17. Кочетков С.Ю. Исследование влияния комбинированного применения ацетилсалициловой кислоты и производных 3-гидроксипиридина и таурина на некоторые показатели гемостаза в эксперименте: дис. … канд. мед. наук. Саранск, 2015. 145 c.

18. Jakl M., Sevcik R., Fatorova I., Horacek J.M., Pudil R. High on-treatment platelet reactivity: risk factors and 5-year outcomes in patients with acute myocardial infarction // Anatol. J. Cardiol. 2017. Vol. 17, N 2. P. 113-118. DOI: 10.14744/AnatolJCardiol.2016.7042.

19. Grotemeyer K.H., Scharafinski H.W., Husstedt I.W. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients // Thromb. Res. 1993. Vol. 71, N 5. P. 397-403. DOI:10.1016/0049-3848(93)90164-j.

20. Mueller M.R., Salat A., Stangl P., Murabito M., Pulaki S., Boehm D., Koppensteiner R., Ergun E., Mittlboeck M., Schreiner W., Losert U., Wolner E. Variable platelet response to lowdose ASA and the risk of limb deterioration in patients submitted to peripheral arterial angioplasty // Thromb. Haemost. 1997. Vol. 78, N 3. P. 1003-1007. DOI: 10.1055/s-0038-1657677.

21. Eikelboom J.W., Hirsh J., Weitz J.I., Johnston M., Yi Q., Yusuf S. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events // Circulation. 2002. Vol. 105, N 14. P. 1650-1655. DOI: 10.1161/01.CIR.0000013777. 21160.07.

22. Chen W.H., Simon D.I. Aspirin response variability and resistance // Аntiplatelet еherapy in ischemic heart disease. Wiley-Blackwell, 2009. P. 47-58. DOI: 10.1002/9781444303339.ch4.

23. Kim J.T., Choi K.H., Park M.S., Lee J.S., Saver J.L., Cho K.H. Clinical significance of acute and serial platelet function testing in acute ischemic stroke // J. Am. Heart Assoc. 2018. Vol. 7, N 11. P. e008313(7). DOI: 10.1161/JAHA.117.008313.

24. Cheng X., Xie N.C., Xu H.L., Chen C., Lian Y.J. Biochemical aspirin resistance is associated with increased stroke severity and infarct volumes in ischemic stroke patients // Oncotarget. 2017. Vol. 8, N 44. P. 77086-177095. DOI: 10.18632/oncotarget. 20356.

25. Neumann F.J., Sousa-Uva M., Ahlsson A., Alfonso F., Banning A.P., Benedetto U., Byrne R.A., Collet J.P., Falk V., Head S.J., Jüni P., Kastrati A., Koller A., Kristensen S.D., Niebauer J., Richter D.J., Seferovic P.M., Sibbing D., Stefanini G.G., Windecker S., Yadav R., Zembala M.O. ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization // Eur. Heart J. 2018. Vol. 00. P. 1-96. DOI: 10.1093/eurheartj/ehy394.

26. Sibbing D., Aradi D., Jacobshagen C., Gross L., Trenk D., Geisler T., Orban M., Hadamitzky M., Merkely B., Kiss R.G., Komócsi A., Dézsi C.A., Holdt L., Felix S.B., Parma R., Klopotowski M., Schwinger R.H.G., Rieber J., Huber K., Neumann F.J., Koltowski L., Mehilli J., Huczek Z., Massberg S. TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial // Lancet. 2017. Vol. 390. P. 1747-1757. DOI: 10.1016/S0140-6736(17)32155-4.

27. Cuisset T., Deharo P., Quilici J., Johnson T.W., Deffarges S., Bassez C., Bonnet G., Fourcade L., Mouret J.P., Lambert M., Verdier V., Morange P.E., Alessi M.C., Bonnet J.L. Benefit of switching dual antiplatelet therapy after acute coronary syndrome: the TOPIC (timing of platelet inhibition after acute coronary syndrome) randomized study // Eur. Heart J. 2017. Vol. 38, N 41. P. 3070-3078. DOI: 10.1093/eurheartj/ehx175.

28. Deharo P., Quilici J., Camoin-Jau L., Johnson T.W., Bassez C., Bonnet G., Fernandez M., Ibrahim M., Suchon P., Verdier V., Fourcade L., Morange P.E., Bonnet J.L., Alessi M.C., Cuisset T. Benefit of switching dual antiplatelet therapy after acute coronary syndrome according to on treatment platelet reactivity: the TOPIC VASP prespecified analysis of the TOPIC randomized study // JACC Cardiovasc. Interv. 2017. Vol. 10, N 24. P. 2560-2570. DOI: 10.1016/j.jcin. 2017.08.044.

29. Costa F., van Klaveren D., James S. et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials // Lancet. 2017. Vol. 389. P. 1025-1034. DOI: 10.1016/S0140-6736(17)30397-5.

30. Wang C.W., Su L.L., Hua Q.J., He Y., Fan Y.N., Xi T.T., Yuan B., Liu Y.X., Ji S.B. Aspirin resistance predicts unfavorable functional outcome in acute ischemic stroke patients // Brain Res. Bull. 2018. Vol. 142. P. 176-182. DOI: 10.1016j.brainresbull.2018.07.004.

31. Чазова И.Е., Ратова Л.Г., Бойцов С.А., Небиеридзе Д.В. Диагностика и лечение артериальной гипертензии (Рекомендации Российского медицинского общества по артериальной гипертонии и Всероссийского научного общества кардиологов) // Систем. гипертензии. 2010. Т. 3. С. 5-27.

32. Born G.V. Aggregation of blood platelets by adenosine diphosphate and reversal // Nature. 1962. Vol. 194. P. 927-929. DOI: 10.1038/194927b0.

33. O’Brien J.R. Variability in the aggregation of human platelets by adrenaline // Nature. 1964. Vol. 202. P. 1188-1190. DOI: 10.1038/2021188a0.

34. Кручинина М.В., Абдуллаева П.А., Громов А.А., Баум В.А., Генералов В.М., Генералов К.В., Кручинин В.Н., Рыхлицкий С.В. Возможности оценки степени тяжести гемореологических нарушений у лиц с артериальной гипертензией // Междунар. журн. прикл. и фундамент. исследований. 2018. № 6. С. 75-84. DOI: 10.17513/mjpfi.12296.

35. Kannel W.B. Risk stratification in hypertension: new insights from the Framingham Study // Am. J. Hypertens. 2000. Vol. 13, N 2. P. 3S-10S. DOI: org/10.1016/S0895-7061(99)00252-6.

36. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений (ВТЭО) // Флебология. 2015. Т. 9, № (4-2). С. 1-52.

37. Баринов В.Е., Лобастов В., Счастливцев И.В., Цаплин С.Н., Лаберко Л.А., Брехов Е.И., Бояринцев В.В. Предикторы развития венозных тромбоэмболических осложнений у оперированных пациентов из группы высокого риска // Флебология. 2014. Т. 8, № 1. С. 21-30.

38. Caprini J.A. Thrombotic risk assessment: A hybrid approach. URL: Availableat: http://www.venousdisease. com/Publications/J.A. Caprini-HybridApproach 3-10-05.pdf (дата обращения: 08.07.17).

39. Шитикова А.С. Тромбоцитарный гемостаз. СПб.: Изд-во СПб. ГМУ, 2000. 227 c.

40. Slatter D.A., Percy C.L., Redpath K.A., Gajsiewicz J.M., Brooks N.J., Clayton A., Tyrrell V.J., Rosas M., Lauder S.N., Watson A., Dul M., Garcia-Diaz Y., Aldrovandi M., Heurich M., Hall J., Morrissey J.H., Lacroix-Desmazes S., Delignat S., Jenkins P.V., Collins P.W., O’Donnell V.B. Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies // JCI Insight. 2018. Vol. 3, N 6. P. e98459(5). DOI: 10.1172/jci.insight.98459.

41. Adili R., Tourdot B.E., Mast K., Yeung J., Freedman J.C., Green A., Luci D.K., Jadhav A., Simeonov A., Maloney D.J., Holman T.R., Holinstat M. First selective 12-LOX inhibitor, ML355, impairs Tthrombus formation and vessel occlusion in vivo with minimal effects on yemostasis // Arterioscler. Thromb. Vasc. Biol. 2017. Vol. 37, N 10. P. 1828-1839. DOI: 10.1161/ATVBAHA.117.309868.

42. Zhang X.J., Cheng X., Yan Z.Z., Fang J., Wang X., Wang W., Liu Z.Y., Shen L.J., Zhang P., Wang P.X., Liao R., Ji Y.X., Wang J.Y., Tian S., Zhu X.Y., Zhang Y., Tian R.F., Wang L., Ma X.L., Huang Z., She Z.G., Li H. An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury // Nature Med. 2018. Vol. 24. P. 73-83. DOI: 10.1038/nm.4451.

43. Yeung J., Tourdot B.E., Fernandez-Perez P., Vesci J., Ren J., Smyrniotis C.J., Luci D.K., Jadhav A., Simeonov A., Maloney D.J., Holman T.R., McKenzie S.E. Holinstat M. Platelet 12-LOX is essential for FcgRIIa-mediated platelet activation // Blood. 2014. Vol. 124. P. 2271-2279. DOI: https://doi.org/10.1182/blood-2014-05-575878.

44. He Z., Peng Y., Duan W., Tian Y., Zhang J., Hu T., Cai Y., Feng Y., Li G. Aspirin regulates hepatocellular lipid metabolism by activating AMPK signaling pathway // J. Toxicol. Sci. 2015. Vol. 40, N 1. P. 127-136. DOI: 10.2131/jts.40.127.

45. Liu L., Gao Y.H., Cao J. et al. High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome // J. Geriatr. Cardiol. 2016. Vol. 13. P. 531-536. DOI: 10.11909/j.issn.1671-5411.2016.06.009.

46. DiNicolantonio J.J., O’Keefe J.H., McCarty M.F. Targeting aspirin resistance with nutraceuticals: a possible strategy for reducing cardiovascular morbidity and mortality // Open Heart. 2017. Vol. 4, N 2. P. e000642(7). DOI: 10.1136/openhrt-2017-000642.

47. Ting H.J., Khasawneh F.T. Platelet function and Isoprostane biology. Should Isoprostanes be the newest member of the Orphan-ligand family? // J. Biomed. Sci. 2010. Vol. 17, N 1. P. 24-31. DOI: 10.1186/1423-0127-17-24.

48. Ivanov I., Heydeck D., Hofheinz K., Roffeis J., O’Donnell V.B., Kuhn H., Walther M. Molecular enzymology of lipoxygenases // Arch. Biochem. Biophys. 2010. Vol. 503, N 2. P. 161-174. DOI: 10.1016/j.abb.2010.08. 016.

49. Ишонина О.Г. Особенности метаболических изменений в крови пациенток с сахарным диабетом 2 типа в зависимости от возраста и степени компенсации углеводного обмена: дис. … канд. биол. наук. Ростов н/Д, 2014. 170 с.


Review

For citations:


Kruchinina M.V., Gromov A.A., Rabko A.V., Abdullaeva P.A., Baum V.A., Generalov V.M., Generalov K.V., Kruchinin V.N., Rykhlitskiy S.V., Shuvalov G.V. ASPIRIN RESISTANCE AS A RISK MARKER FOR VENOUS THROMBOEMBOLIC COMPLICATIONS. Ateroscleroz. 2018;14(4):40-55. (In Russ.) https://doi.org/10.15372/ATER20180405

Views: 493


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2078-256X (Print)
ISSN 2949-3633 (Online)