Venous thromboembolism is a common complication in patients with cancer. The management of deep vein thrombosis and pulmonary embolism can be a considerable challenge in patients with cancer. The cancer itself and associated treatments contribute to an ongoing thrombogenic stimulus, while cancer patients are thought to be at increased risk for anticoagulant-induced bleeding. Initial treatment of acute thromboembolism is with intravenous unfractionated heparin or subcutaneous low molecular weight heparin. Treatment at home with low molecular weight heparin is an attractive option in patients with malignant disease. Long-term treatment of acute venous thromboembolism has traditionally been with oral anticoagulants. However, the inconvenience and narrow therapeutic window of oral anticoagulants make such therapy unattractive and problematic in cancer patients. Low molecular weight heparins are being evaluated as an alternative for long-term therapy because their anticoagulant effects are more predictable and laboratory monitoring is unnecessary. Although many clinical issues remain unresolved in the treatment of cancer patients with venous thromboembolism, the future holds much promise as new antithrombotic agents, including factor Xa antagonists and oral thrombin inhibitors, are being tested in clinical trials.

1.
Hyers TM, Agnelli A, Hull RD, et al: Antithrombotic therapy for venous thromboembolic disease. Chest 1998;114(suppl 5):561S–578S.
2.
Levine MN, Hirsh J, Gent M, et al: A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin. Arch Intern Med 1994;154:49–56.
3.
Weitz JI: Low molecular weight heparins. N Engl J Med 1997;337:688–698.
4.
Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG: Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330–1335.
5.
Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM: Low molecular weight heparins compared with unfractionated heparin for treatment of acute deep vein thrombosis. A meta-analysis of randomized controlled trials. Ann Intern Med 1999;130:800–809.
6.
Hull RD, Raskob GE, Pineo GF, et al: Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992;326:975–982.
7.
Prandoni P, Lensing AWA, Buller HR, et al: Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992;339:441–445.
8.
Levine M, Gent M, Hirsh J, et al: A comparison of low molecular weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis. N Engl J Med 1996;334:677–681.
9.
Koopman MW, Prandoni P, Piovella F, et al: Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low molecular weight heparin administered at home. N Engl J Med 1996;334:682–687.
10.
The Columbus Investigators: Low molecular weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997;337:657–662.
11.
Harrison L, McGinnis J, Crowther M, Ginsberg J, Hirsh J: Assessment of outpatient treatment of deep vein thrombosis with low molecular weight heparin. Arch Intern Med 1998;158:2001–2003.
12.
Wells PS, Kovacs MJ, Bormanis J, Forgie MA, Goudie D, Morrow B, Kovacs J: Expanding eligibility for outpatient treatment of deep vein thrombosis and pulmonary embolism with low molecular weight heparin. Arch Intern Med 1998;158:1809–1812.
13.
Levine M, Raskob G, Landefeld CS, Kearon C: Hemorrhagic complications of anticoagulant treatment. Chest 1998;114(suppl):511S–523S.
14.
Hirsh J, Dalen JE, Anderson D, et al: Oral anticoagulants: Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998;114(suppl):445S–469S.
15.
Woerner EM, Rowe RL: Trousseau’s syndrome. Am Fam Physician 1998;38:195–201.
16.
Chan A, Woodruff RK: Complications and failure of anticoagulation therapy in the treatment of venous thromboembolism in patients with disseminated malignancy. Aust NZ J Med 1992;22:119–122.
17.
Norrby K: Heparin and angiogenesis: A low-molecular-weight fraction inhibits and a high-molecular-weight fraction stimulates angiogenesis systemically. Haemostasis 1993;23(suppl 1):141–149.
18.
Pini M, Aiello S, Manotti C, et al: Low molecular weight heparin versus warfarin in the prevention of recurrences after deep vein thrombosis. Thromb Haemost 1994;72:191–197.
19.
Lopaciuk S, Bielska-Falda H, Noszczyk W, et al: Low molecular weight heparin versus acenocoumarol in the secondary prophylaxis of deep vein thrombosis. Thromb Haemost 1999;81:26–31.
20.
Veiga F, Escriba A, Maluenda P, et al: Low molecular weight heparin (enoxaparin) versus oral anticoagulant therapy (acenocoumarol) in the long-term treatment of deep venous thrombosis in the elderly: A randomized trial. Thromb Haemost 2000;84:559–564.
21.
Hull R, Pineo G, Mah A, et al: Long-term low molecular weight heparin treatment versus oral anticoagulant therapy for proximal deep vein thrombosis (abstract). Blood 2000;96:449a.
22.
Schulman S, Rhedin A-S, Lindmarker P, et al: A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. N Engl J Med 1995;332:1661–1665.
23.
Schulman S, Granqvist S, Holmström M, et al: The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. N Engl J Med 1997;336:393–398.
24.
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;340:901–907.
25.
Gitter MJ, Jaeger TM, Petterson TM, et al: Bleeding and thromboembolism during anticoagulant therapy: A population-based study in Rochester, Minnesota. Mayo Clin Proc 1995;70:725–733.
26.
van der Meer FJM, Rosendaal FR, Vandenbroche JP, et al: Bleeding complication in oral anticoagulant therapy. Arch Intern Med 1993;153:1557–1562.
27.
Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen J, Buller HR: Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: A retrospective analysis. J Clin Oncol 2000;18:3078–3083.
28.
Palareti G, Legnani C, Lee A, et al: A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost 2000;84:805–810.
29.
Prandoni P, Lensing AWA, Cogo A, et al: The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1–7.
30.
Bona RD, Sivjee KY, Hickey AD, et al: The efficacy and safety of oral anticoagulation in patients with cancer. Thromb Haemost 1995;74:1055–1058.
31.
Heit JA, Mohr DN, Silverstein, et al: Predictors of recurrence after deep vein thrombosis and pulmonary embolism. A population-based cohort study. Arch Intern Med 2000;160:761–768.
32.
Hansson PO, Sorbo J, Eriksson H: Recurrent venous thromboembolism after deep vein thrombosis, incidence and risk factors. Arch Intern Med 2000;160:769–774.
33.
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. Prévention du Risque d’Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med 1998;338:409–415.
34.
Choucair AK, Silver P, Levin VA: Risk of intracranial hemorrhage in glioma patients receiving anticoagulant therapy for venous thromboembolism. J Neurosurg 1987;66:357–358.
35.
Altschuler E, Moosa H, Selker RG, et al: The risk and efficacy of anticoagulant therapy in the treatment of thromboembolic complications in patients with primary malignant brain tumors. Neurosurgery 1990;27:74–77.
36.
Schiff D, DeAngelis LM: Therapy of venous thromboembolism in patients with brain metastases. Cancer 1994;73:493–498.
37.
Norris LK, Grossman SA: Treatment of thromboembolic complications in patients with brain tumors. J Neurooncol 1994;22:127–137.
38.
So W, Hugenholtz A, Richard MT: Complications of anticoagulant therapy in patients with known central nervous system lesions. Can J Surg 1983;26:181–183.
39.
Schwarz RE, Marrero AM, Conlon KC, et al: Inferior vena cava filters in cancer patients: Indications and outcomes. J Clin Oncol 1996;14:652–657.
40.
Wentzien TH, O’Reilly RA, Kearns PJ: Prospective evaluation of anticoagulant reversal with oral vitamin K1 while continuing warfarin therapy unchanged. Chest 1998;114:1546–1550.
41.
Crowther MA, Julian J, McCarty D, Douketis J, Kovacs M, Biagoni L, Schnurr T, McGinnis J, Gent M, Hirsh J, Ginsberg J: Treatment of warfarin-associated coagulopathy with oral vitamin K: A randomized controlled trial. Lancet 2000;356:1551–1553.
42.
Hirsh J, Weitz JI: New antithrombotic agents. Lancet 1999;353:1431–1436.
43.
Walenga JM, Heske WP, Bara L, et al: Biochemical and pharmacologic rationale for the development of a synthetic heparin pentasaccharide. Thromb Res 1997;86:1–36.
44.
Lassen MR: The EPHESUS study: Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin: The prevention of venous thromboembolism (VTE) after elective hip replacement surgery (abstract). Blood 2000;96:490a.
45.
Eriksson B: The PENTHIFRA study: Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin: The prevention of venous thromboembolism (VTE) after hip fracture surgery (abstract). Blood 2000;96:490a.
46.
Bauer K: The PENTAMAKS study: Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin: The prevention of venous thromboembolism (VTE) after elective major knee surgery (abstract). Blood 2000;96:490a.
47.
Turpie G: The PENTATHLON 2000 study: Comparison of the first synthetic factor Xa inhibitor with low molecular weight heparin in the prevention of venous thromboembolism (VTE) after elective hip replacement surgery (abstract). Blood 2000;96:491a.
48.
Eriksson BI, Arfwidsson A-C, Sareyko Elvander C, et al: Subcutaneous and oral direct thrombin inhibitors for prophylaxis of deep venous thrombosis and pulmonary embolism after total hip and knee replacement (abstract). Blood 1999;94(suppl 1):589a.
49.
Eriksson H, Eriksson UG, Frison L, et al: Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT. Thromb Haemost 1999;81:358–363.
50.
Heit J, Colwell CW, Francis CW, et al: Comparison of the oral direct thrombin inhibitor H376/95 with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: A phase II dose-finding study (abstract). Blood 2000;96:491a.
51.
Rebello SS, Blank HS, Rote WE, et al: Antithrombotic efficacy of a recombinant nematode anticoagulant peptide (rNAP5) in canine models of thrombosis after single subcutaneous administration. J Pharmacol Exp Ther 1997;283:91–99.
52.
Lee A, Agnelli G, Büller H, et al: A dose-response study of the factor VIIa/tissue factor inhibitor rNAPc2 in the prevention of postoperative venous thromboembolism in patients undergoing total knee arthroplasty (abstract). Blood 2000;96:491a.
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