Selective intra-arterial thrombolysis in acute limb ischemia

• Kalinin R.E.
• Klimentova E.A.
• Pshennikov A.S.
• Egorov A.A.
• Suchkov I.A.

Abstract

Despite significant advances in modern treatment of patients with peripheral artery disease, acute limb ischemia remains highly prevalent, limb-threatening, and potentially fatal, continuing to pose a challenge to vascular surgeons. Currently, there are various approaches to managing patients with acute limb ischemia. Selective intra-arterial thrombolysis is an acceptable alternative to surgical treatment. To date, the main indications, advantages and complications of thrombolysis have been identified. Searching for prognostic risk factors for the development of hemorrhagic complications and the likelihood of adverse outcomes after selective intra-arterial thrombolysis can help in choosing a treatment method for patients with this disease. However, despite the introduction of new thrombolytic drugs and improved infusion techniques of selective intra-arterial thrombolysis, the long-term results of vascular patency have not significantly improved and are in fact comparable to those in the urokinase era. Therefore, the prevention of reocclusion by means of additional pharmacological agents is an area that is under development and is being actively studied using numerous approaches, including the use of modern anticoagulant and antiplatelet drugs.

Funding. The study had no financial support.

Conflict of interest. The authors declare no conflicts of interest.

Authors’ contribution. Study conception and design – Kalinin R.E., Klimentova E.A., Pshennikov A.S., Egorov A.A., Suchkov I.A.; data collection and handling – Klimentova E.A., Egorov A.A.; draft manuscript preparation – Klimentova E.A.; manuscript revision – Kalinin R.E., Pshennikov A.S., Suchkov I.A

For citation: Kalinin R.E., Klimentova E.A., Pshennikov A.S., Egorov A.A., Suchkov I.A. Selective intra-arterial thrombolysis in acute limb ischemia. Angiology and Vascular Surgery. Journal named after Academician A.V. Pokrovsky. 2024; 30 (1): 7–17. DOI: https://doi.org/10.33029/1027-6661-2024-30-1-7-17

Keywords: acute limb ischemia; selective intra-arterial thrombolysis; reocclusion of the vascular wall; thrombotic masses; vascular conduit

References

1. Galyfos G., Chamzin A., Intzes N., et al. Acute limb ischemia. Journal of Cardiovascular Surgery. 2023; 64 (4): 396–405. DOI: https://doi.org/10.23736/S0021–9509.22.12536–X

2. Fluck F., Augustin A.M., Bley T., Kickuth R. Current Treatment Options in Acute Limb Ischemia. Rofo. 2020; 192 (4): 319–326. DOI: https://doi.org/10.1055/a–0998–4204

3. Kalinin R.E., Suchkov I.A., Mzhavanadze N.D., et al. Nitric oxide metabolites in the development of complications after open reconstructive interventions in patients with peripheral atherosclerosis. Eruditio Juvenium. 2021; 9 (3): 407–414. DOI: https://doi.org/10.23888/HMJ202193407–414 (in Russian)

4. Kalinin R.E., Suchkov I.A., Mzhavanadze N.D., Korotkova N.V., Nikiforov A.A., Surov I.Y., Ivanova P.Y., Bozhenova A.D., Strelnikova E.A. Comparison of cytotoxicity of vascular prostheses in vitro. 2020; 28 (2): 183–192. DOI: https://doi.org/10.23888/PAVLOVJ2020282183–192 (in Russian)

5. Kulezic A., Acosta S. Epidemiology and Prognostic Factors in Acute Lower Limb Ischaemia: A Population Based Study. European Journal of Vascular and Endovascular Surgery. 2022; 63 (2): 296–303. DOI: https://doi.org/10.1016/j.ejvs.2021.10.044

6. Rosenberg H., Rosenberg E., Kubelik D. Acute limb ischemia. Canadian Medical Association Journal. 2023; 195 (40): E1383. DOI: https://doi.org/10.1503/cmaj.230471

7. Luan T.M.B., Bang H.T., Tan N.M., et al. Catheter–directed intra–arterial thrombolysis in the treatment of acute thrombosis of below–the–knee arteries. Radiology Case Reports. 2021; 16 (8): 2086–2090. DOI: https://doi.org/10.1016/j.radcr.2021.05.012

8. Ouriel K., Shortell C.K., DeWeese J.A., et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. Journal of Vascular Surgery. 1994; 19 (6): 1021–1030. DOI: https://doi.org/10.1016/s0741–5214(94)70214–4

9. Results of a prospective randomized trial evaluating surgery versus thrombolysis for ischemia of the lower extremity. The STILE trial. Annals of Surgery. 1994; 220 (3): 251–266. DOI: https://doi.org/10.1097/00000658–199409000–00003

10. Ouriel K., Veith F.J., Sasahara A.A. A comparison of recombinant urokinase with vascular surgery as initial treatment for acute arterial occlusion of the legs. Thrombolysis or Peripheral Arterial Surgery (TOPAS) Investigators. The New England Journal of Medicine. 1998; 338 (16): 1105–1111. DOI: https://doi.org/10.1056/NEJM199804163381603

11. Taha A.G., Byrne R.M., Avgerinos E.D., et al. Comparative effectiveness of endovascular versus surgical revascularization for acute lower extremity ischemia. Journal of Vascular Surgery. 2015; 61 (1): 147–154. DOI: 10.1016/j.jvs.2014.06.109

12. Dragas M., Zlatanovic P., Koncar I., et al. Effect of Intra–operative Intra–arterial Thrombolysis on Long Term Clinical Outcomes in Patients with Acute Popliteal Artery Aneurysm Thrombosis. European Journal of Vascular and Endovascular Surgery. 2020; 59 (2): 255–264. DOI: 10.1016/j.ejvs.2019.10.013

13. Shi T., Zhang Y., Shen C., Fang J. A single–centre protocol using low–dose urokinase for catheter–directed thrombolysis in the treatment of acute lower limb ischaemia. Vascular. 2023; 17085381231174922. DOI: https://doi.org/10.1177/17085381231174922

14. Güneş Y., Sincer I., Erdal E. Catheter–directed intra–arterial thrombolysis for lower extremity arterial occlusions. The Anatolian Journal of Cardiology. 2019; 22 (2): 54–59. DOI: https://doi.org/10.14744/AnatolJCardiol.2019.63296

15. Chait J., Aurshina A., Marks N., et al. Comparison of Ultrasound–Accelerated Versus Multi–Hole Infusion Catheter–Directed Thrombolysis for the Treatment of Acute Limb Ischemia. Vascular and Endovascular Surgery. 2019; 53 (7): 558–562. DOI: https://doi.org/10.1177/1538574419861768

16. Khan S., Hawkins B.M. Acute Limb Ischemia Interventions. Interventional Cardiology Clinics. 2020; 9 (2): 221–228. DOI: https://doi.org/10.1016/j.iccl.2019.12.002

17. Broderick C., Patel J.V. Infusion techniques for peripheral arterial thrombolysis. Cochrane Database and Systematic Reviews. 2021; 11 (11): CD000985. DOI: 10.1002/14651858.CD000985.pub3

18. Berridge D.C., Gregson R.H.S., Hopkinson B.R., Makin G.S. Randomized trial of intra–arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra–arterial streptokinase in peripheral arterial thrombolysis. British Journal of Surgery. 1991; 78 (8): 988–995. DOI: https://doi.org/10.1002/bjs.1800780831

19. Saroukhani A., Ravari H., Pezeshki R.M. Effects of Intravenous and Catheter Directed Thrombolytic Therapy with Recombinant Tissue Plasminogen Activator (Alteplase) in Non–Traumatic Acute Limb Ischemia; A Randomized Double–Blind Clinical Trial. Bulletin of Emergency And Trauma. 2015; 3 (3): 86–92.

20. Braithwaite B.D., Buckenham T.M., Galland R.B., et al. Prospective randomized trial of high–dose bolus versus low–dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group. British Journal of Surgery. 1997; 84 (5): 646–650.

21. Yusuf S.W., Whitaker S.C., Gregson R.H., et al. Prospective randomised comparative study of pulse spray and conventional local thrombolysis. European Journal of Vascular and Endovascular Surgery. 1995; 10 (2): 136–141. DOI: https://doi.org/10.1016/s1078–5884(05)80104–2

22. Duda S.H., Tepe G., Luz O., et al. Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone – a randomized pilot trial (the PROMPT study). Platelet receptor antibodies in order to manage peripheral artery thrombosis. Radiology. 2001; 221 (3): 689–696. DOI: https://doi.org/10.1148/radiol.2213010400

23. Comerota A.J., Davidovic L., Hanna K., et al. Phase 2, randomized, open–label study on catheter–directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion. Journal of Drug Assessment. 2019; 8 (1): 43–54. DOI: https://doi.org/10.1080/21556660.2019.1586402

24. Vakhitov D., Oksala N., Saarinen E., et al. Survival of Patients and Treatment–Related Outcome After Intra–Arterial Thrombolysis for Acute Lower Limb Ischemia. Annals of Vascular Surgery. 2019; 55: 251–259. DOI: https://doi.org/10.1016/j.avsg.2018.07.041

25. Björck M., Earnshaw J.J., Acosta S., et al. European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. European Journal of Vascular and Endovascular Surgery. 2020; 59: 173–218. DOI: https://doi.org/10.1016/j.ejvs.2019.09.006

26. Jongkind V., Earnshaw J.J., Gonçalves F.B., et al. Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in light of the COVID–19 pandemic, based on a scoping review of the literature. European Journal of Vascular and Endovascular Surgery. 2022; 63 (1): 80–89. DOI: https://doi.org/10.1016/j.ejvs.2021.08.028

27. Theodoridis P.G., Davos C.H., Dodos I., et al. Thrombolysis in Acute Lower Limb Ischemia: Review of the Current Literature. Annals of Vascular Surgery. 2018; 52: 255–262. DOI: https://doi.org/10.1016/j.avsg.2018.02.030

28. Vakhitov D., Oksala N., Saarinen E., et al. Survival of Patients and Treatment–Related Outcome After Intra–Arterial Thrombolysis for Acute Lower Limb Ischemia. Annals of Vascular Surgery. 2019; 55: 251–259. DOI: https://doi.org/10.1016/j.avsg.2018.07.041

29. Darwood R., Berridge D.C., Kessel D.O., et al. Surgery versus thrombolysis for initial management of acute limb ischaemia. Cochrane Database and Systematic Reviews. 2018; 8 (8): CD002784. DOI: https://doi.org/10.1002/14651858

30. Sandbaek G., Staxrud L.E., Rosen L., et al. Factors predicting the outcome of intraarterial thrombolysis in peripheral arterial and graft occlusions. Acta Radiologica. 1996; 37 (3Pt1): 299–304. DOI: 10.1177/02841851960371P163

31. Schrijver A.M., de Vries J.P., van den Heuvel D.A., Moll F.L. Long–Term Outcomes of Catheter–Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts. Annals of Vascular Surgery. 2016; 31: 134–142. DOI: https://doi.org/10.1016/j.avsg.2015.08.026

32. Liu X., Xie H., Zheng G., Liu Y. The plasma D–dimer trends and their value in acute lower limb ischemia patients treated by catheter directed thrombolysis. Scientific Reports. 2021; 11 (1): 10388. DOI: https://doi.org/10.1038/s41598–021–89905–x

33. Ouriel K., Shortell C.K., Azodo M.V., et al. Acute peripheral arterial occlusion: predictors of success in catheter–directed thrombolytic therapy. Radiology. 1994; 193 (2): 561–566. DOI: https://doi.org/10.1148/radiology.193.2.7972780

34. Plate G., Oredsson S., Lanke J. When is thrombolysis for acute lower limb ischemia worthwhile? European Journal of Vascular and Endovascular Surgery. 2009; 37 (2): 206–212. DOI: https://doi.org/10.1016/j.ejvs.2008.11.010

35. Earnshaw J.J., Whitman B., Foy C. National Audit of Thrombolysis for Acute Leg Ischemia (NATALI): clinical factors associated with early outcome. Journal of Vascular Surgery. 2004; 39 (5): 1018–1025. DOI: https://doi.org/10.1016/j.jvs.2004.01.019

36. Clouse M.E., Stokes K.R., Perry L.J., Wheeler H.G. Percutaneous intraarterial thrombolysis: analysis of factors affecting outcome. Journal of Vascular and Interventional Radiology. 1994; 5 (1): 93–100. DOI: https://doi.org/10.1016/s1051–0443(94)71461–5

37. Bagoly Z., Szegedi I., Kálmándi R., et al. Markers of Coagulation and Fibrinolysis Predicting the Outcome of Acute Ischemic Stroke Thrombolysis Treatment: A Review of the Literature. Frontiers in Neurology. 2019; 10: 513. DOI: https://doi.org/10.3389/fneur.2019.00513

38. Miles L.A., Ny L., Wilczynska M., et al. Plasminogen Receptors and Fibrinolysis. International Journal of Molecular Sciences. 2021; 22 (4): 1712. DOI: https://doi.org/10.3390/ijms22041712

39. Garcia–Avello A., Garcia–Frade L.J., Gandarias C., et al. High F1.2 fragment of prothrombin, thrombin–antithrombin III complex (TAT) and soluble fibrin plasma levels demonstrate hypercoagulability induced during loco–regional thrombolytic therapy with rt–PA. Thrombosis Research. 1994; 73 (2): 109–115. DOI: https://doi.org/10.1016/0049–3848(94)90085–x

40. Gram J., Munkvad S., Leebeek F.W., et al. Reactive coagulation induced by plasmin in patients treated with recombinant tissue–type plasminogen activator. Coronary artery disease. 1993; 4 (4): 371–377. DOI: https://doi.org/10.1097/00019501–199304000–00009

41. Hvas C.L., Larsen J.B. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. International Journal of Molecular Sciences. 2023; 24 (18): 14179. DOI: https://doi.org/10.3390/ijms241814179

42. Schrijver A.M., de Vries J.P., van den Heuvel D.A., Moll F.L. Long–Term Outcomes of Catheter–Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts. Annals of Vascular Surgery. 2016; 31: 134–142. DOI: https://doi.org/10.1016/j.avsg.2015.08.026

43. Koupenova M., Clancy L., Corkrey H.A., Freedman J.E. Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis. Circulation Research. 2018; 122 (2): 337–351. DOI: https://doi.org/10.1161/CIRCRESAHA.117.310795

44. Vakhitov D., Hakovirta H., Saarinen E., et al. Prognostic risk factors for recurrent acute lower limb ischemia in patients treated with intra–arterial thrombolysis. Journal of Vascular Surgery. 2020; 71 (4): 1268–1275. DOI: https://doi.org/10.1016/j.jvs.2019.07.061

45. Nicolini F.A., Lee P., Malycky J.L., et al. Selective inhibition of factor Xa during thrombolytic therapy markedly improves coronary artery patency in a canine model of coronary thrombosis. Blood Coagulation & Fibrinolysis. 1996; 7 (1): 39–48. DOI: https://doi.org/10.1097/00001721–199601000–00005

46. Nicolini F.A., Lee P., Rios G., et al. Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. Circulation. 1994; 89 (4): 1802–1809. DOI: https://doi.org/10.1161/01.cir.89.4.1802

47. Leadley R.J. Jr., Kasiewski C.J., Bostwick J.S., et al. Comparison of enoxaparin, hirulog, and heparin as adjunctive antithrombotic therapy during thrombolysis with rtPA in the stenosed canine coronary artery. Thrombosis and Haemostasis. 1997; 78 (4): 1278–1285.

48. Rebello S.S., Bentley R.G., Morgan S.R., et al. Antithrombotic efficacy of a novel factor Xa inhibitor, FXV673, in a canine model of coronary artery thrombolysis. British Journal of Pharmacology. 2001; 133 (7): 1190–1198. DOI: https://doi.org/10.1038/sj.bjp.0704182

49. Abendschein D.R., Baum P.K., Verhallen P., et al. A novel synthetic inhibitor of factor Xa decreases early reocclusion and improves 24–h patency after coronary fibrinolysis in dogs. Journal of Pharmacology and Experimental Therapeutics. 2001; 296 (2): 567–572.

50. Ammollo C.T., Semeraro F., Incampo F., et al. Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin–activatable fibrinolysis inhibitor. Journal of Thrombosis and Haemostasis. 2010; 8 (4): 790–798. DOI: https://doi.org/10.1111/j.1538–7836.2010.03739.x

51. Steffel J., Eikelboom J.W., Anand S.S., et al. The COMPASS Trial: Net Clinical Benefit of Low–Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients With Chronic Vascular Disease. Circulation. 2020; 142 (1): 40–48. DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.046048

16. Khan S., Hawkins B.M. Acute Limb Ischemia Interventions. Interventional Cardiology Clinics. 2020; 9 (2): 221-228. DOI: https://doi.org/10.1016/j.iccl.2019.12.002

17. Broderick C., Patel J.V. Infusion techniques for peripheral arterial thrombolysis. Cochrane Database and Systematic Reviews. 2021; 11 (11): CD000985. DOI: 10.1002/14651858.CD000985.pub3

18. Berridge D.C., Gregson R.H.S., Hopkinson B.R., Makin G.S. Randomized trial of intra-arterial recombinant tissue plasminogen activator, intravenous recombinant tissue plasminogen activator and intra-arterial streptokinase in peripheral arterial thrombolysis. British Journal of Surgery. 1991; 78 (8): 988-995. DOI: https://doi.org/10.1002/bjs.1800780831

19. Saroukhani A., Ravari H., Pezeshki R.M. Effects of Intravenous and Catheter Directed Thrombolytic Therapy with Recombinant Tissue Plasminogen Activator (Alteplase) in Non-Traumatic Acute Limb Ischemia; A Randomized Double-Blind Clinical Trial. Bulletin of Emergency And Trauma. 2015; 3 (3): 86-92.

20. Braithwaite B.D., Buckenham T.M., Galland R.B., et al. Prospective randomized trial of high-dose bolus versus low-dose tissue plasminogen activator infusion in the management of acute limb ischaemia. Thrombolysis Study Group. British Journal of Surgery. 1997; 84 (5): 646-650.

21. Yusuf S.W., Whitaker S.C., Gregson R.H., et al. Prospective randomised comparative study of pulse spray and conventional local thrombolysis. European Journal of Vascular and Endovascular Surgery. 1995; 10 (2): 136-141. DOI: https://doi.org/10.1016/s1078-5884(05)80104-2

22. Duda S.H., Tepe G., Luz O., et al. Peripheral artery occlusion: treatment with abciximab plus urokinase versus with urokinase alone - a randomized pilot trial (the PROMPT study). Platelet receptor antibodies in order to manage peripheral artery thrombosis. Radiology. 2001; 221 (3): 689-696. DOI: https://doi.org/10.1148/radiol.2213010400

23. Comerota A.J., Davidovic L., Hanna K., et al. Phase 2, randomized, open-label study on catheter-directed thrombolysis with plasmin versus rtPA and placebo in acute peripheral arterial occlusion. Journal of Drug Assessment. 2019; 8 (1): 43-54. DOI: https://doi.org/10.1080/21556660.2019.1586402

24. Vakhitov D., Oksala N., Saarinen E., et al. Survival of Patients and Treatment-Related Outcome After Intra-Arterial Thrombolysis for Acute Lower Limb Ischemia. Annals of Vascular Surgery. 2019; 55: 251-259. DOI: https://doi.org/10.1016/j.avsg.2018.07.041

25. Björck M., Earnshaw J.J., Acosta S., et al. European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia. European Journal of Vascular and Endovascular Surgery. 2020; 59: 173-218. DOI: https://doi.org/10.1016/j.ejvs.2019.09.006

26. Jongkind V., Earnshaw J.J., Gonçalves F.B., et al. Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in light of the COVID-19 pandemic, based on a scoping review of the literature. European Journal of Vascular and Endovascular Surgery. 2022; 63 (1): 80-89. DOI: https://doi.org/10.1016/j.ejvs.2021.08.028

27. Theodoridis P.G., Davos C.H., Dodos I., et al. Thrombolysis in Acute Lower Limb Ischemia: Review of the Current Literature. Annals of Vascular Surgery. 2018; 52: 255-262. DOI: https://doi.org/10.1016/j.avsg.2018.02.030

28. Vakhitov D., Oksala N., Saarinen E., et al. Survival of Patients and Treatment-Related Outcome After Intra-Arterial Thrombolysis for Acute Lower Limb Ischemia. Annals of Vascular Surgery. 2019; 55: 251-259. DOI: https://doi.org/10.1016/j.avsg.2018.07.041

29. Darwood R., Berridge D.C., Kessel D.O., et al. Surgery versus thrombolysis for initial management of acute limb ischaemia. Cochrane Database and Systematic Reviews. 2018; 8 (8): CD002784. DOI: https://doi.org/10.1002/14651858

30. Sandbaek G., Staxrud L.E., Rosen L., et al. Factors predicting the outcome of intraarterial thrombolysis in peripheral arterial and graft occlusions. Acta Radiologica. 1996; 37 (3Pt1): 299-304. DOI: 10.1177/02841851960371P163

31. Schrijver A.M., de Vries J.P., van den Heuvel D.A., Moll F.L. Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts. Annals of Vascular Surgery. 2016; 31: 134-142. DOI: https://doi.org/10.1016/j.avsg.2015.08.026

32. Liu X., Xie H., Zheng G., Liu Y. The plasma D-dimer trends and their value in acute lower limb ischemia patients treated by catheter directed thrombolysis. Scientific Reports. 2021; 11 (1): 10388. DOI: https://doi.org/10.1038/s41598-021-89905-x

33. Ouriel K., Shortell C.K., Azodo M.V., et al. Acute peripheral arterial occlusion: predictors of success in catheter-directed thrombolytic therapy. Radiology. 1994; 193 (2): 561-566. DOI: https://doi.org/10.1148/radiology.193.2.7972780

34. Plate G., Oredsson S., Lanke J. When is thrombolysis for acute lower limb ischemia worthwhile? European Journal of Vascular and Endovascular Surgery. 2009; 37 (2): 206-212. DOI: https://doi.org/10.1016/j.ejvs.2008.11.010

35. Earnshaw J.J., Whitman B., Foy C. National Audit of Thrombolysis for Acute Leg Ischemia (NATALI): clinical factors associated with early outcome. Journal of Vascular Surgery. 2004; 39 (5): 1018-1025. DOI: https://doi.org/10.1016/j.jvs.2004.01.019

36. Clouse M.E., Stokes K.R., Perry L.J., Wheeler H.G. Percutaneous intraarterial thrombolysis: analysis of factors affecting outcome. Journal of Vascular and Interventional Radiology. 1994; 5 (1): 93-100. DOI: https://doi.org/10.1016/s1051-0443(94)71461-5

37. Bagoly Z., Szegedi I., Kálmándi R., et al. Markers of Coagulation and Fibrinolysis Predicting the Outcome of Acute Ischemic Stroke Thrombolysis Treatment: A Review of the Literature. Frontiers in Neurology. 2019; 10: 513. DOI: https://doi.org/10.3389/fneur.2019.00513

38. Miles L.A., Ny L., Wilczynska M., et al. Plasminogen Receptors and Fibrinolysis. International Journal of Molecular Sciences. 2021; 22 (4): 1712. DOI: https://doi.org/10.3390/ijms22041712

39. Garcia-Avello A., Garcia-Frade L.J., Gandarias C., et al. High F1.2 fragment of prothrombin, thrombin-antithrombin III complex (TAT) and soluble fibrin plasma levels demonstrate hypercoagulability induced during loco-regional thrombolytic therapy with rt-PA. Thrombosis Research. 1994; 73 (2): 109-115. DOI: https://doi.org/10.1016/0049-3848(94)90085-x

40. Gram J., Munkvad S., Leebeek F.W., et al. Reactive coagulation induced by plasmin in patients treated with recombinant tissue-type plasminogen activator. Coronary artery disease. 1993; 4 (4): 371-377. DOI: https://doi.org/10.1097/00019501-199304000-00009

41. Hvas C.L., Larsen J.B. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. International Journal of Molecular Sciences. 2023; 24 (18): 14179. DOI: https://doi.org/10.3390/ijms241814179

42. Schrijver A.M., de Vries J.P., van den Heuvel D.A., Moll F.L. Long-Term Outcomes of Catheter-Directed Thrombolysis for Acute Lower Extremity Occlusions of Native Arteries and Prosthetic Bypass Grafts. Annals of Vascular Surgery. 2016; 31: 134-142. DOI: https://doi.org/10.1016/j.avsg.2015.08.026

43. Koupenova M., Clancy L., Corkrey H.A., Freedman J.E. Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis. Circulation Research. 2018; 122 (2): 337-351. DOI: https://doi.org/10.1161/CIRCRESAHA.117.310795

44. Vakhitov D., Hakovirta H., Saarinen E., et al. Prognostic risk factors for recurrent acute lower limb ischemia in patients treated with intra-arterial thrombolysis. Journal of Vascular Surgery. 2020; 71 (4): 1268-1275. DOI: https://doi.org/10.1016/j.jvs.2019.07.061

45. Nicolini F.A., Lee P., Malycky J.L., et al. Selective inhibition of factor Xa during thrombolytic therapy markedly improves coronary artery patency in a canine model of coronary thrombosis. Blood Coagulation & Fibrinolysis. 1996; 7 (1): 39-48. DOI: https://doi.org/10.1097/00001721-199601000-00005

46. Nicolini F.A., Lee P., Rios G., et al. Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. Circulation. 1994; 89 (4): 1802-1809. DOI: https://doi.org/10.1161/01.cir.89.4.1802

47. Leadley R.J. Jr., Kasiewski C.J., Bostwick J.S., et al. Comparison of enoxaparin, hirulog, and heparin as adjunctive antithrombotic therapy during thrombolysis with rtPA in the stenosed canine coronary artery. Thrombosis and Haemostasis. 1997; 78 (4): 1278-1285.

48. Rebello S.S., Bentley R.G., Morgan S.R., et al. Antithrombotic efficacy of a novel factor Xa inhibitor, FXV673, in a canine model of coronary artery thrombolysis. British Journal of Pharmacology. 2001; 133 (7): 1190-1198. DOI: https://doi.org/10.1038/sj.bjp.0704182

49. Abendschein D.R., Baum P.K., Verhallen P., et al. A novel synthetic inhibitor of factor Xa decreases early reocclusion and improves 24-h patency after coronary fibrinolysis in dogs. Journal of Pharmacology and Experimental Therapeutics. 2001; 296 (2): 567-572.

50. Ammollo C.T., Semeraro F., Incampo F., et al. Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin-activatable fibrinolysis inhibitor. Journal of Thrombosis and Haemostasis. 2010; 8 (4): 790-798. DOI: https://doi.org/10.1111/j.1538-7836.2010.03739.x

51. Steffel J., Eikelboom J.W., Anand S.S., et al. The COMPASS Trial: Net Clinical Benefit of Low-Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients With Chronic Vascular Disease. Circulation. 2020; 142 (1): 40-48. DOI: https://doi.org/10.1161/CIRCULATIONAHA.120.046048

All articles in our journal are distributed under the CC BY-NC-ND 4.0 (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International)

п?? GEOTAR-Media Publishing Group. The use of textual and illustrative content from this publication for the training of any artificial intelligence systems п?? including machine learning models and neural networks п?? is strictly prohibited without the prior written consent of the copyright holder.