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Mechanisms of Thrombosis

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Thrombolysis in Pulmonary Embolism

Abstract

In the era of translational medicine, clinical and molecular evidence provide several links between inflammation and pulmonary embolism suggesting a close relationship among atherothrombosis risk factors and venous thrombosis. Inflammation, a well-established pathway driven by interleukin-expression, could induce endothelial veins activity and vascular disease. Additionally, acute infections with collateral thrombosis mechanisms could have an important role. Considering all evidence linking inflammation with pulmonary embolism, it is possible that new elements have to be included in a contemporary viewpoint of Virchow’s triad and that unprovoked or idiopathic pulmonary embolism term has to be redefined. Currently, with the combination of improved models of venous thromboembolism and high-resolution microscopy techniques, new evidence linking molecular, cellular mechanisms, platelets and innate immune cells with venous thrombosis have been identified. Thrombosis triggered by systemic hypoxemia is mediated by tissue factor induction in macrophages following activation of the transcription factor early growth response-1 gene. This transcription factor with hypoxia inducible factor-1 is also an important transcription factor mediating adaptive responses to hypoxia in endothelium; in vitro, these responses include proinflammatory and pro-adhesive changes. Finally, pathologic evidence shows left and right myocarditis associated with endocardium thrombosis in patients who died secondary to pulmonary embolism.

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References

  1. Furie F, Furie BC. Mechanisms of thrombus formation. N Engl J Med. 2008;359:938–49.

    Article  CAS  PubMed  Google Scholar 

  2. Steffel J, Braunwald E. Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J. 2011;32:1968–76.

    Article  CAS  PubMed  Google Scholar 

  3. Kroce K, Libby P. Intertwining of thrombosis and inflammation in atherosclerosis. Curr Opin Hematol. 2007;14:55–61.

    Article  Google Scholar 

  4. Kaski JC, Arrebola-Moreno AL. Inflammation and thrombosis in atrial fibrillation. Rev Esp Cardiol. 2011;64:551–3.

    Article  PubMed  Google Scholar 

  5. Inoue T, Croce K, Morooka T, Sakuma M, Node K, Simon DI. Vascular inflammation and repair. J Am Coll Cardiol Intv. 2011;4:1057–66.

    Article  Google Scholar 

  6. Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet. 2006;367:1075–9.

    Article  PubMed  Google Scholar 

  7. Jerjes-Sanchez C. Venous and arterial thrombosis. A continuum spectrum of the same disease? Eur Heart J. 2005;26:1–2.

    Article  Google Scholar 

  8. Prandoni P, Bilora F, Marchiori A, Bernardi E, Peitrobeli F, Lensing AWA, Prins MH, Girolami A. An association between atherosclerosis and venous thrombosis. N Engl J Med. 2003;348:1435–41.

    Article  PubMed  Google Scholar 

  9. Becattini C, Agnelli G, Prandoni P, Silingardi M, Salvi R, Taliani MR, Poggio R, de Imberti D, Ageno W, Pogliani E, Porro F, Casazza F. A prospective study on cardiovascular events after acute pulmonary embolism. Eur Heart J. 2005;26:77–83.

    Article  PubMed  Google Scholar 

  10. Libby P, Crea F. Clinical implications of inflammation for cardiovascular primary prevention. Eur Heart J. 2010;31:777–83.

    Article  CAS  PubMed  Google Scholar 

  11. Libby P, Ridker PM, Hansson GK, for the Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54:2129–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Glynn RJ, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, Mac Fadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Ridker PM. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009;360:1851–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Piazza G, Goldhaber ZS. Venous thromboembolism and atherotrombosis. An integrated approach. Circulation. 2010;121:2146–50.

    Article  PubMed  Google Scholar 

  14. Goldhaber ZS. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010;56:1–7.

    Article  PubMed  Google Scholar 

  15. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A. 1987;84:9265–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Palmer RM, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987;327:524–6.

    Article  CAS  PubMed  Google Scholar 

  17. Marcus AJ, Broekman MJ, Pinsky DJ. COX inhibitors and thromboregulation. N Engl J Med. 2002;347:1025–6.

    Article  PubMed  Google Scholar 

  18. Lerman A, Zeiher AM. Endothelial function: cardiac events. Circulation. 2005;111:363–8.

    Article  PubMed  Google Scholar 

  19. Gorog DA. Prognostic value of plasma fibrinolysis activation markers in cardiovascular disease. J Am Coll Cardiol. 2010;55:2701–9.

    Article  CAS  PubMed  Google Scholar 

  20. Capodanno D, Angiolillo DJ. Antithrombotic therapy in the elderly. J Am Coll Cardiol. 2010;56:1683–92.

    Article  CAS  PubMed  Google Scholar 

  21. De Caterina R, Husted S, Wallentin L, Andreotti F, Arnesen H, Bachmann F, Baigent C, Huber K, Jespersen J, Kristensen SD, Lip GYH, Morais J, Rasmussen LH, Siegbahn A, Verheugt FWA, Weitz JI. General mechanisms of anticoagulation and targets of anticoagulants. Thromb Haemost. 2013;109:569–79.

    Google Scholar 

  22. Gurbel PA, Tantry US. Antiplatelet and anticoagulant agents in heart failure. J Am Coll Cardiol. 2014;2:1–14.

    Google Scholar 

  23. Dubois C, Panicot-Dubois L, Gainor JF, Furie BC, Furie B. Thrombin-initiated platelet activation in vivo is vWF independent during thrombus formation in a laser injury model. J Clin Invest. 2007;117:953–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Dahlback B. Blood coagulation. Lancet. 2000;355:1627–32.

    Article  CAS  PubMed  Google Scholar 

  25. Schreiner PJ, Morrisett JD, Sharrett AR, Patsch W, Tyroler HA, Wu K, Heiss G. Lipoprotein(a) as a risk factor for preclinical atherosclerosis. Arterioscler Thromb. 1993;3:826–33.

    Article  Google Scholar 

  26. Sotiriou SN, Orlova VV, Al-Fakhri N, Ihanus E, Economopoulou M, Isermann B, Bdeir K, Nawroth PP, Preissner KT, Gahmberg CG, Koschinsky ML, Chavakis T. Lipoprotein (a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin. FASEB J. 2006;20:559–61.

    CAS  PubMed  Google Scholar 

  27. Gouni-Berthold I, Berthold HK. Lipoprotein (a): current perspectives. Curr Vasc Pharmacol. 2011;9:682–92.

    Article  CAS  PubMed  Google Scholar 

  28. Tsimikas S, Witztum JL. The role of oxidized phospholipids in mediating lipoprotein (a) atherogenicity. Curr Opin Lipidol. 2008;19:369–77.

    Article  CAS  PubMed  Google Scholar 

  29. Ichikawa T, Unoki H, Sun H, Shimoyamada H, Marcovina S, Shikama H, Watanabe T, Fan J. Lipoprotein (a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo (a) transgenic rabbits. Am J Pathol. 2002;160:227–36.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Scherz N, Labarére J, Aujesky D, Méan M. Elevated admission glucose and mortality in patients with pulmonary embolism. Diabetes Care. 2012;35:25–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Schermuly RT, Ghofrani HA, Wilkins MR, Grimminger F. Mechanisms of disease: pulmonary arterial hypertension. Nat Rev Cardiol. 2011;8:443–55.

    Article  CAS  PubMed  Google Scholar 

  32. Libby P, Simon DI. Inflammation and thrombosis: the clot thickens. Circulation. 2001;103:1718–20.

    Article  CAS  PubMed  Google Scholar 

  33. Liuzzo G, Santamaria M, Biasucci LM, Narducci M, Colafrancesco V, Porto A, Brugaletta S, Pinnelli M, Rizzello V, Maseri A, Crea F. Persistent activation of nuclear factor kappa-ß signaling pathway in patients with unstable angina and elevated levels of C-reactive protein. J Am Coll Cardiol. 2007;49:185–94.

    Article  CAS  PubMed  Google Scholar 

  34. Riveiro A, Lindmarker P, Johnson H, Juhlin-Dannfelt A, Jorfeldt L. Pulmonary embolism: one-year follow-up with echocardiography Doppler and five-year survival analysis. Circulation. 1999;99:1325–30.

    Article  Google Scholar 

  35. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism; clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386–9.

    Article  CAS  PubMed  Google Scholar 

  36. Jerjes-Sanchez C, Elizalde GJ, Sandoval JZ, Gutierrez-Fajardo P, Seoane DLM, Ramirez-Rivera A, Pulido T, Beltran M, Santos E, Bautista E, Ibarra-Perez C, Arriaga-Nava R. Diagnostico, estratificacion y tratamiento de la tromboembolia pulmonar aguda. Guias y Recomendaciones del Capitulo de Circulacion Pulmonar de la Sociedad Mexicana de Cardiologia. Arch Cardiol Mex. 2004;74 Suppl 3:S547–85.

    Google Scholar 

  37. AHA Scientific Statement from American Heart Association. Management of massive and submassive pulmonary embolism, ileofemoral deep venous thrombosis and chronic thromboembolic pulmonary hypertension. Circulation. 2011;123:1788–830.

    Article  Google Scholar 

  38. The Task Force on the diagnosis and management of acute pulmonary embolism of the European Cardiology Society. Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J. 2008;29:2276–315.

    Google Scholar 

  39. Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347:1143–50.

    Article  CAS  PubMed  Google Scholar 

  40. Meneveau N, Mingb LP, Seronde MF, Mersina N, Schielea F, Caulfield F, Bernard Y, Bassand JP. In-hospital and long-term outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy. Eur Heart J. 2003;24:1447–54.

    Article  PubMed  Google Scholar 

  41. Goldhaber SZ, Come PC, Lee RT, Brauwald LT, Parker JA, Haire WD, Feldstein ML, Miller M, Toltzis R, Smith JL, Taveira de Silva AM, Mogtader A, McDonough TJ. Alteplase versus heparin in acute pulmonary embolism; randomized trial assessing right-ventricular function and pulmonary perfusion. Lancet. 1993;341:507–511.

    Google Scholar 

  42. Jerjes-Sanchez C, Villarreal-Umaña S, Ramirez-Rivera A, Garcia-Sosa A, Canseco LM, Archondo T, Reyes E, Garza A, Arriaga R, Castillo F, Jasso O, Garcia H, Bermudez M, Hernández JM, Garcia J, Martinez P, Rangel F, Gutierrez J, Comparan A. Improving adjunctive treatment in pulmonary embolism and fibrinolytic therapy. The role of enoxaparin and weight-adjusted unfractionated heparin. J Thromb Thrombolysis. 2009;27:154–62.

    Article  CAS  PubMed  Google Scholar 

  43. Jerjes-Sanchez C, Ramirez-Rivera A, Arriaga-Nava R, Iglesias-Gonzalez S, Gutierrez P, Ibarra-Perez C, Martinez A, Valencia S, Rosado-Buzzo A, Pierzo JA, Rosas E. High-dose and short-term streptokinase infusion in patients with pulmonary embolism. Prospective with seven-year follow-up trial. J Thromb Thrombolysis. 2001;12:237–47.

    Article  CAS  PubMed  Google Scholar 

  44. Jerjes-Sanchez C, Ramirez-Rivera A, Garcia ML, Arriaga-Nava R, Valencia-Sanchez S, Rosado-Buzzo A, Pierzo JA, Rosas ME. Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomized controlled trial. J Thromb Thrombolysis. 1995;2:67–9.

    Article  Google Scholar 

  45. Lualdi JC, Goldhaber SZ. Right ventricular dysfunction after acute pulmonary embolism: pathophysiologic factors, detection, and therapeutic implications. Am Heart J. 1995;130:1276–82.

    Article  CAS  PubMed  Google Scholar 

  46. Begieneman MVP, Van de Goot FRW, Van der Bilt IAC, Vonk Noordegraaf C, Spreeuwenberg MD, Paulus WJ, Van Hinsbergh VWM, Visser FC, Niessen HWM. Pulmonary embolism causes endomyocarditis in the human heart. Heart. 2008;94:450–6.

    Article  CAS  PubMed  Google Scholar 

  47. Iwadate K, Tanno K, Doi M, et al. Two cases of right ventricular ischemic injury due to massive pulmonary embolism. Forensic Sci Int. 2001;116:189–95.

    Article  CAS  PubMed  Google Scholar 

  48. Iwadate K, Doi M, Tanno K, et al. Right ventricular damage due to pulmonary embolism: examination of the number of infiltrating macrophages. Forensic Sci Int. 2003;134:147–53.

    Article  PubMed  Google Scholar 

  49. Key NS. Bench to bedside: new developments in our understanding of the pathophysiology of thrombosis. J Thromb Thrombolysis. 2013;35:342–5.

    Article  PubMed  Google Scholar 

  50. Hamer JD, Malone PC, Silver IA. The PO2 in venous valve pockets: its possible bearing on thrombogenesis. Br J Surg. 1981;68:166–70.

    Article  CAS  PubMed  Google Scholar 

  51. Lawson CA, Yan SD, Yan SF, Liao H, Zhou YS, Sobel J, Kisiel W, Stern DM, Pinsky DJ. Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation. J Clin Invest. 1997;99:1729–38.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Reitsma PH, Rosendaal FR. Past and future of genetic research in thrombosis. J Thromb Haemost. 2007;5 Suppl 1:264–9.

    Article  CAS  PubMed  Google Scholar 

  53. Kaplan MJ, Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol. 2012;189:2689–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Manly DA, Boles J, Mackman N. Role of tissue factor in venous thrombosis. Annu Rev Physiol. 2011;73:515–25.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. Rautou PE, Mackman N. Microvesicles as risk markers for venous thrombosis. Expert Rev Hematol. 2013;6:91–101.

    Article  CAS  PubMed  Google Scholar 

  56. Brooks EG, Trotman W, Wadsworth MP, Taatjes DJ, Evans MF, Ittleman FP, Callas PW, Esmon CT, Bovill EG. Valves of the deep venous system: an overlooked risk factor. Blood. 2009;114:1276–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Instituto de Cardiologia y Medicina Vascular, TEC Salud, San Pedro Garza Garcia, Nuevo León, Mexico

    Carlos Jerjes-Sánchez M.D., F.C.C.P., F.A.C.C. (Sistema Nacional de Investigadores, Nivel II – Clinical Research Director)

  2. Escuela de Medicina, Tecnológico de Monterrey, San Pedro Garza Garcia, Nuevo León, Mexico

    Carlos Jerjes-Sánchez M.D., F.C.C.P., F.A.C.C. (Sistema Nacional de Investigadores, Nivel II – Clinical Research Director)

  3. Unidad de Investigacion Clinica en Medicina SC, Monterrey, Nuevo León, Mexico

    Carlos Jerjes-Sánchez M.D., F.C.C.P., F.A.C.C. (Sistema Nacional de Investigadores, Nivel II – Clinical Research Director)

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  1. Carlos Jerjes-Sánchez M.D., F.C.C.P., F.A.C.C.
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Correspondence to Carlos Jerjes-Sánchez M.D., F.C.C.P., F.A.C.C. .

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Jerjes-Sánchez, C. (2015). Mechanisms of Thrombosis. In: Thrombolysis in Pulmonary Embolism. Springer, Cham. https://doi.org/10.1007/978-3-319-19707-4_1

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  • DOI: https://doi.org/10.1007/978-3-319-19707-4_1

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-19706-7

  • Online ISBN: 978-3-319-19707-4

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