Abstract

Acute pulmonary embolism (PE) is a common presentation on the acute medical take. In our previous article in Vol 6 issue 1 we discussed the diagnostic approach to this condition. This article concentrates on the treatment of PE, including guidance for treatment of PE in pregnancy and cancer. This article also discusses the role of alternative anticoagulants, thrombolysis, surgery and inferior vena caval filters.
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References

1. Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979–1998: an analysis using multiple-cause mortality data. Arch Intern Med 2003; 163: 1711.
2. Dismuke SE, Wagner EH. Pulmonary embolism as a cause of death. The changing mortality in hospitalized patients. JAMA 1986; 255: 2039.
3. Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis 1975; 17: 257.
4. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1991; 151: 933.
5. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 401s.
6. Carson JL, Kelley MA, Duff A, et al. The clinical course of pulmonary embolism. N Engl J Med 1992; 326: 1240.
7. Donaldson GA, Williams C, Schnnel JG, et al. A reappraisal of the application of the Trendelenburg operation to massive fatal embolism. Report of a successful pulmonary-artery thrombectomy using a cardiopulmonary bypass. N Engl J Med 1963; 268: 171.
8. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1991; 151: 933.
9. Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 287S.
10. Hull RD, Raskob GE, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med 1986; 315: 1109.
11. Raschke RA, Reilly BM, Guidry JR, et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. Ann Intern Med 1993; 119: 874.
12. Barrit DW, Jordan SC. Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial. Lancet 1960; 1: 1309.
13. Kernohan RJ, Todd C. Heparin therapy in thromboembolic disease. Lancet 1966; 1: 621.
14. Alpert JS, Smith R, Carlson J, et al. Mortality in patients treated for pulmonary embolism. JAMA 1976; 236: 1477.
15. Kanis JA. Heparin in the treatment of pulmonary thromboembolism. Thromb Diath Haemorrh 1974; 32: 519.
16. Simonneau G, Sors H, Charbonnier B, et al. A comparison of lowmolecular-weight heparin with unfractionated heparin for acute pulmonary embolism. The THESEE Study Group. Tinzaparine ou Heparine Standard: Evaluations dans l’Embolie Pulmonaire. N Engl J Med 1997; 337: 663.
17. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000; 83: 209.
18. Merli G, Spiro TE, Olsson CG, et al. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med 2001; 134: 191.
19. Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 287S.
20. Stein PD, Hull RD, Raskob GE. Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial noninvasive leg tests. Am J Med 2000; 109: 301.
21. van Dongen CJ, van den Belt AG, Prins MH, et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Database Syst Rev 2004; : CD001100.
22. Buller HR, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 401S.
23. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337: 688.
24. Al-Yaseen E, Wells PS, Anderson J, et al. The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients. J Thromb Haemost 2005; 3: 100.
25. Hainer JW, Barrett JS, Assaid CA, et al. Dosing in heavy-weight/obese patients with the LMWH, tinzaparin: a pharmacodynamic study. Thromb Haemost 2002; 87: 817.
26. Wells PS, Anderson DR, Rodger MA, et al. A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism. Arch Intern Med 2005; 165: 733.
27. Hochberg EP, Chillemi AC, Wu CJ, et al. Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults. Blood 2001; 98: 1116.
28. Beer JH, Burger M, Gretener S, et al. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost 2003; 1: 186.
29. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with dalteparin. Thromb Haemost 2000; 83: 209.
30. Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology. Eur Heart J 2000; 21: 1301.
31. Levine MN, Raskob G, Beyth RJ, et al. Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 287S.
32. Hull R, Delmore T, Genton E, et al. Warfarin sodium versus low-dose heparin in the long-term treatment of venous thrombosis. N Engl J Med 1979; 301: 855.
33. Hull R, Delmore T, Carter C, et al. Adjusted subcutaneous heparin versus warfarin sodium in the long-term treatment of venous thrombosis. N Engl J Med 1982; 306: 189.
34. Ridker PM, Goldhaber SZ, Danielson E, et al. Long-term, low-intensity warfarin therapy for the prevention of recurrent venous thromboembolism. N Engl J Med 2003; 348: 1425.
35. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006; :CD001367.
36. Agnelli G, Prandoni P, Becattini C, et al. Extended oral anticoagulant therapy after a first episode of pulmonary embolism. Ann Intern Med 2003; 139: 19.
37. Kearon C, Gent M, Hirsh J, et al. A comparison of three months of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999; 340: 901.
38. Palareti G, Cosmi B, Legnani C, et al. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006; 355: 1780.
39. Meneveau N, Seronde MF, Blonde MC, et al. Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest 2006; 129: 1043.
40. Schulman S, Granqvist S, Holmstrom M, et al. The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group. N Engl J Med 1997; 336: 393.
41. Hull R, Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 1982; 307: 1676–1681.
42. Turpie AGG, Gunstensen J, Hirsh J, et al. Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet 1988; 1: 1242–1245.
43. Saour JN, Sieck JO, Mamo LAR, et al. Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N Engl J Med 1990; 322: 428–432.
44. Altman R, Rouvier J, Gurfinkel E, et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991; 101: 427–431.
45. Kearon C, Ginsberg JS, Kovacs MJ, et al. Comparison of low-intensity warfarin therapy with conventional-intensity warfarin therapy for longterm prevention of recurrent venous thromboembolism. New England Journal of Medicine 2003; 349: 631–639.
46. Ridker PM. Long-term low-dose warfarin use is effective in the prevention of recurrent venous thromboembolism: yes. Journal of Thrombosis and Haemostasis 2004; 2: 1034–1037.
47. Bern MM, Lokich JJ, Wallach SR, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. Ann Intern Med 1990; 112: 423–428.
48. Brandjes DP, Heijboer H, Buller HR, et al. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximalvein thrombosis. N Engl J Med 1992; 327: 1485.
49. Anand SS, Bates S, Ginsberg JS, et al. Recurrent venous thrombosis and heparin therapy: an evaluation of the importance of early activated partial thromboplastin times. Arch Intern Med 1999; 159: 2029.
50. Linkins LA, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a metaanalysis. Ann Intern Med 2003; 139: 893.
51. The Matisse Investigators. Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. N Engl J Med 2003; 349: 1695–1702.
52. Buller HR, Davidson BL, Decousus H, et al. Fondaparinux or enoxaparin for the initial treatment of symptomatic deep venous thrombosis. Ann Intern Med 2004; 140: 867–873.
53. Turpie AG, Fisher WD, Bauer KA, et al. BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study. J Thromb Haemost 2005; 3: 2479.
54. Eriksson BI, Borris L, Dahl OE, et al. Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement. J Thromb Haemost 2006; 4: 121.
55. Kucher N, Goldhaber SZ. Management of massive pulmonary embolism. Circulation 2005; 112: e28.
56. Mathru M, Venus B, Smith RA, et al. Treatment of low cardiac output complicating acute pulmonary hypertension in normovolemic goats. Crit Care Med 1986; 14: 120.
57. Molloy WD, Lee KY, Girling L, et al. Treatment of shock in a canine model of pulmonary embolism. Am Rev Respir Dis 1984; 130: 870.
58. Boulain T, Lanotte R, Legras A. Efficacy of epinephrine therapy in shock complicating acute PE. Chest 1993; 104: 300.
59. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999; 353: 1386–1389.
60. Kasper W, Konstantinides S, Greibel A, et al. Management strategies and determinants of outcome in acute pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997; 30: 1165–71.
61. Arcasoy SM, Kreit JW. Thrombolytic therapy of pulmonary embolism: a comprehensive review of current evidence. Chest 1999; 115: 1695–1707.
62. Urokinase Pulmonary Embolism Trial: phase 1 results; a cooperative study. JAMA 1970; 214: 2163–2172.
63. Tibbutt DA, Davies JA, Anderson JA, et al. Comparison by controlled clinical trial of streptokinase and heparin in treatment of life-threatening pulmonary embolism. BMJ 1974; 1: 343–347.
64. Ly B, Arnesen H, Erie H, et al. A controlled trial of streptokinase and heparin in the treatment of major pulmonary embolism. Acta Med Scand 1978; 203: 465–470.
65. Marini C, DiRicco G, Rossi G, et al. Fibrinolytic effects of urokinase and heparin in acute pulmonary embolism: a randomized clinical trial. Respiration 1988; 54: 162–173.
66. PIOPED Investigators. Tissue plasminogen activator for the treatment of acute pulmonary embolism: a collaborative study by the PIOPED investigators. Chest 1990; 97: 528–533.
67. Levine M, Hirsh J, Weitz J, et al. A randomized trial of a single bolus dosage regimen of recombinant tissue plasminogen activator in patients with acute pulmonary embolism. Chest 1990; 98: 1473–1479.
68. Dalla-Volta S, Palla A, Santolicandro A, et al. PAIMS 2: alteplase combined with heparin versus heparin in the treatment of acute pulmonary embolism. J Am Coll Cardiol 1992; 20: 520–526.
69. Kasper W, Konstantinides S, Geibel A, et al. Prognostic significance of right ventricular afterload stress detected by echocardiography in patients with clinically suspected pulmonary embolism. Heart 1997; 77: 346–349.
70. Wan S, Quinlan DJ, Agnelli G, et al. Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation 2004; 110: 744–749.
71. Mikkola K, Patel S, Parker J, et al. Increasing age is a risk factor for haemorrhagic complications after pulmonary embolism. Am Heart J 1997; 134: 69–72.
72. Dalen J. Thrombolytic therapy for pulmonary embolism, is it effective? Is it safe? When is it indicated? Arch Int Med 1997; 157: 2250–6.
73. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003; 58: 470–83.
74. Decousus H, Leizorovicz A, Parent F, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. N Engl J Med 1998; 338: 409.
75. Recommended reporting standards for vena caval filter placement and patient follow-up. J Vasc Interv Radiol 2003; 14: S427.
76. White RH, Zhou H, Kim J, et al. A population based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism. Arch Intern Med 2000; 160(13): 2033–2041.
77. Ku GH, Billet HH. Long lives, short indications. The case for removable inferior vena caval filters. Thromb Haemost 2005; 93: 17.
78. Baglin TP, Brush J, Streiff M. Guidelines on the use of vena caval filters. Br J Haematol 2006.
79. Buller HR, Agnelli G, Hull RD. Antithrombotic therapy for venous thromboembolic disease; The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest 2004; 126: 401S.
80. Neill AM, Appleton DS, Richards P. Retrievable inferior vena caval filter for thromboembolic disease in pregnancy. Br J Obstet Gynaecol 1997; 104(12): 1416–18.
81. Zwaan M, Lorch H, Kulke C, et al. Clinical experience with temporary vena caval filters. J Vasc Interv Radiol 1998; 9(4): 594–601.
82. Baglin TP, Brush J, Streiff M. Guidelines on use of vena cava filters British Journal of Haematology 2006; 134(6): 590–595.
83. Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection. Arch Intern Med 1998; 158: 1809–1812.
84. Meyer G, Marjanovic Z, Valcke J, et al. Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer. Arch Intern Med 2002; 162: 1729–1735.
85. Lee AY, Levine MN, Baker RI, et al. Low-molecular- weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349: 146-153.
86. Monreal M, Zacharski L, Jimenez JA, et al. Fixed-dose low-molecularweight heparin for secondary prevention of venous thromboembolism in patients with disseminated cancer: a prospective cohort study. J Thromb Haemost 2004; 2: 1311–1315.
87. Prandoni P, Falanga A. Piccioli A, Cancer and venous thromboembolism. Lancet Oncol 2005; 6: 401–410.
88. Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 2005; 128: 291–302.
89. Cruickshank MK, Levine MN, Hirsh J, et al. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151: 333–337.
90. Thromboemebolic Disease in Pregnancy and the Puerperium: Acute Management. Thomson AJ & Greer IA. Royal College of Obstetricians and Gynaecologists, RCOG press, London. Guideline No 28, 2001.
91. Ellison J, Walker ID, Greer IA. Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy. Brit J Obstet and Gynacol 2000; 107: 1116–1121.
92. Greer IA, Nelson-Piercy C. Low-molecular weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy. A systematic review of safety and efficacy. Blood 2005; 106: 401–407.
93. Sanson BJ, Lensing AW, Prins MH, et al. Safety of low-molecular-weight heparin in pregnancy: A systematic review. Thromb Haemost 1999; 81: 668–672.
94. Forestier F, Daffos F, Capella-Pavlovsky M. Low molecular weight heparin (PK 10169) does not cross the placenta during the second trimester of pregnancy: study by direct fetal blood sampling under ultrasound. Thromb Res 1984; 34: 557–60.
95. Forestier F, Daffos F, Rainaut M, et al. Low molecular weight heparin (CY 216) does not cross the placenta during the third trimester of pregnancy. Thromb Haemost 1987; 57: 234.
96. Blomback M, Bremme K, Hellgren M, et al. A pharmacokinetic study of dalteparin (Fragmin) during late pregnancy. Blood Coag Fibrinol 1998; 9: 343–50.
97. Casele HL, Laifer SA, Woelkers DA, et al. Changes in the pharmacokinetics of the low molecular weight heparin enoxaparin sodium during pregnancy. Am J Obstet Gynecol 1999; 181: 1113–17.
98. Greer IA, Hunt BJ. Low molecular weight heparin in pregnancy: Current Issues. Br J Haematol 2005; 128: 593–601.
99. Ahearn et al Massive pulmonary embolism during pregnancy successfully treated with recombinant tissue plasminogen activator: A case report and review of the treatment options. Arch Int Med 2002; 162: 1221–7.
100. O’Shaughnessy D, Miles J,Wimperis J. UK Patients with deep-vein thrombosis can be safely treated as outpatients. QJ Med 2000; 93: 663–7.
101. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003; 58: 470–83.
102. Wells PS, Kovacs MJ, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low molecular weight heparin. Arch Intern Med 1998; 158: 1809–1812.
103. Kovacs MJ, Anderson D, Morrow B, et al. Outpatient treatment of pulmonary embolism with Dalteparin. Thromb Haemost 2000; 83: 209–211.
104. Moser KM, Fedullo PF, LittleJohn JK, et al. Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis. JAMA 1994; 271(3): 223–5.
105. Plate G, Ohlin P, Eklof B. Pulmonary embolism in acute iliofemoralvein thrombosis. Br J Surg 1985; 72(11): 912–5.
106. Rowlinson JS, J Deagle J, Roseveare CD. Ambulatory investigation and treatment of patients with suspected pulmonary embolism: a retrospective review of one year’s experience. J R Coll Physicians Edinb 2006; 36: 12–16.