ABSTRACT

Venous thromboembolism represents a spectrum of the same entity which includes pulmonary embolism and deep vein thrombosis. The conventional anticoagulation with unfractionated heparin and low-molecular-weight heparin for 5-10 days is the initial treatment of choice. Pulmonary embolism treatment typically continues with vitamin K antagonists between 3 and 6 months, in some cases anticoagulation is up to 1 year, due to the latency of risk factors. Several studies have confirmed the effectiveness and safety of low-molecular-weight heparin compared with unfractionated heparin in the acute phase treatment of pulmonary embolism; nowadays the use of the latter is routine in both prevention and treatment of deep-vein thrombosis. This differs from the treatment of massive and/or submassive pulmonary embolism requiring fibrinolytic therapy because mortality is up to 70%, strongly related to right ventricular failure and heart failure.

KEYWORDS

Venous thromboembolic disease, pulmonary thromboembolism, unfractionated heparin, low-molecular-weight heparin, vitamin K antagonists.

REFERENCES

1. Moser KM, Fedullo PF, LitteJohn JK, Crawford R. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA 1994;271(3):223-225.

2. Kasper W, Konstantinides S, Geibel A, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997;30(5):1165-1171.

3. Jerjes-Sánchez C, Elizalde GJJ, Sandoval ZJ, et al. Diagnóstico, estratificación y tratamiento de la tromboembolia pulmonar aguda. Guías y recomendaciones del Capítulo de Circulación Pulmonar de la Sociedad Mexicana de Cardiología. Arch Cardiol Mex 2004;74(3 Supl): S547-S585.

4. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet 1960;1(7138):1309-1312.

5. Task Force on Pulmonary Embolism, European Society of Cardiology. Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J 2000;21(16):1301-1336.

6. Ruiz MJ, Andreo GM. Tratamiento médico del tromboembolismo pulmonar. En: Juretschke MA, Barbosa AC, editores. Tromboembolismo pulmonar. Monografías NEUMOMADRID. Vol. IV. España: NEUMOMADRID, Doyma; 2002.p.111-130.

7. Tapson VF. Acute pulmonary embolism. N Engl J Med 2008;358(10):1037-1052.

8. Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. JAMA 1998;279(6):458-462.

9. Conti S, Daschbach M, Blaisdell FW. A comparison of high-dose versus conventional dose heparin therapy for deep vein thrombosis. Surgery 1982;92(6):972-980.

10. Warkentin TE, Kelton JG. A 14-year study of heparin induced thrombocytopenia. Am J Med 1996;101(5):502-507.

11. Villagómez A, Alcántar E, Avelar F, et al. Guías para el diagnóstico, prevención y tratamiento de la enfermedad tromboembólica venosa. Med Inter Mex 2006;22:S1-S37.

12. Kearon C. Long-term management of patients after venous thromboembolism. Circulation 2004;110(9 Suppl 1):110-18.

13. Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G; American College of Chest Physicians. Oral anticoagulant therapy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e44S-e88S.

14. Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1995;108(4 Suppl):335S-351S.

15. Remy-Jardin M, Pistolesi M, Goodman LR, et al. Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. Radiology 2007;245(2):315-329.

16. Quinlan DJ, McQuillan A, Eikelboom JW. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta analysis of randomized, controlled trials. Ann Intern Med 2004;140(3):175-183.

17. Jaff MR, McMurtry MS, Archer SL, et al; American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; American Heart Association Council on Peripheral Vascular Disease; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011;123(16):1788-1830.

18. Garcia DA, Baglin TP, Weitz JI, Samama MM; American College of Chest Physicians. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e24S-e43S.

19. Brandjes DP, Heijboer H, Büller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992;327(21):1485-1489.

20. Fasco MJ, Hildebrandt EF, Suttie JW. Evidence that warfarin anticoagulant action involves two distinct reductase activities. J Biol Chem 1982;257(19):11210-11212.

21. Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost 2005;93(5):872-875.

22. Kurnik D, Loebstein R, Rabinovitz H, Austerweil N, Halkin H, Almog S. Over-the-counter vitamin K1-containing multivitamin supplements disrupt warfarin anticoagulation in vitamin K1-depleted patients. A prospective, controlled trial. Thromb Haemost 2004;92(5):1018-1024.

23. Choonara IA, Malia RG, Haynes BP, et al. The relationship between inhibition of vitamin K1 2,3-epoxide reductase and reduction of clotting factor activity with warfarin. Br J Clin Pharmacol 1988;25(1):1-7.

24. Forfar JC. Prediction of hemorrhage during long-term oral coumarin anticoagulation by excessive prothrombin ratio. Am Heart J 1982;103(3):445-446.

25. Toschi V, Lettino M, Gallo R, Badimon JJ, Chesebro JH. Biochemistry and biology of hirudin. Coron Artery Dis 1996;7(6):420-428.

26. Lewis BE, Walenga JM, Wallis DE. Anticoagulation with Novastan (argatroban) in patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome. Semin Thromb Hemost 1997;23(2):197-202.

27. Connolly SJ, Ezekowitz MD, Yusuf S, et al.; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361(12):1139-1151.

28. Schulman S, Kearon C, Kakkar AK, et al.; RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009;361(24):2342-2352.

29. Vargas RAG, Ramírez LAN, Medina VME. Nuevos anticoagulantes: dabigatrán, rivaroxabán y apixabán. Gac Méd Méx 2012;148(3):257-264.

30. Bauersachs R, Berkowitz SD, Brenner B, et al.; EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363(26):2499-2510.

31. Büller HR, Prins MH, Lensin AW, et al.; EINSTEIN-PE investigadores. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366(14):1287-1297.

32. Kearon C, Akl EA, Comerota AJ, et al.; American College of Chest Physicians. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S-494S.

33. Arcasoy SM, Kreit JW. Thrombolytic therapy of pulmonary embolism: a comprehensive review of current evidence. Chest 1999;115(6):1695-1707.

34. Monreal M, Casals A, Las Heras G, et al. Hemorragias por heparina en el tratamiento del tromboembolismo venoso. Angiología 1990;42(1):11-15.

35. Mikkola KM, Patel SR, Parker JA, Grodstein F, Goldhaber SZ. Increasing age is a major risk factor for hemorrhagic complications after pulmonary embolism thrombolysis. Am Heart J 1997;134(1):69-72.

36. The urokinase pulmonary embolism trial (UPET). A national cooperative study. Circulation 1973;47(2 Suppl):II1-130.

37. Meyer G, Gisselbrecht M, Diehl JL, Journois D, Sors H. Incidence and predictors of major hemorrhagic complications from thrombolytic therapy in patients with massive pulmonary embolism. Am J Med 1998;105(6):472-477.

38. Kanter DS, Mikkola KM, Patel SR, Parker JA, Goldhaber SZ. Thrombolytic therapy for pulmonary embolism. Frequency of intracranial hemorrhage and associated risk factors. Chest 1997;111(5):1241-1245.

39. Tibbutt DA, Davies JA, Anderson JA, et al. Comparison by controlled clinical trial of streptokinase and heparin in treatment of life-threatening pulmonary embolism. Br Med J 1974;1(5904):343-347.

40. Dalla-Volta S, Palla A, Santolicandro A, et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. Plasminogen activator Italian multicenter study 2. J Am Coll Cardiol 1992;20(3):520-526.

41. Nauffal MD, Modesto AM, Ansótegui BE. Diagnóstico y tratamiento del tromboembolismo pulmonar hemodinámicamente inestable. En: Juretschke MMA, Barbosa AC, editores. Tromboembolismo pulmonar. Monografías NEUMOMADRID. Vol. IV. España: NEUMOMADRID, Doyma; 2002. pp. 131-148.

42. Leeper KV Jr, Popovich J Jr, Lesser BA, et al. Treatment of massive acute pulmonary embolism. The use of low doses of intrapulmonary arterial streptokinase combined with full doses of systemic heparin. Chest 1988;93(2):234-240.

43. Mackman N. Triggers, targets and treatments for thrombosis. Nature 2008;451(7181):914-918.

44. Raschke RA, Gollihare B, Peirce JC. The effectiveness of implementing the weight-based heparin nomogram as a practice guideline. Arch Intern Med 1996;156(15):1645-1649.

45. Torbicki A, Perrier A, Konstantinides S, et al. ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29(18):2276-2315.

46. Stein PD, Hull RD, Raskob G. Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism. Consideration of noninvasive management. Ann Intern Med 1994;121(5):313-317.