ABSTRACT
Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Its management remains challenging because patients with a cancer-associated thrombosis are at higher risk of recurrent VTE than are noncancer subjects with thrombosis and also have a greater risk for anticoagulant-associated bleeding complications while receiving therapy to prevent recurrent VTE. Recently, anticoagulant strategies based on the administration of low-molecular-weight heparin (LMWH) rather than vitamin K antagonists for up to 6 days to prevent recurrent VTE have been evaluated. These studies indicate that LMWH is associated with a lower rate for recurrent VTE and similar rates of bleeding when compared with oral anticoagulant therapy. Chronic exposure to LMWH may also prolong survival of cancer patients.
KEYWORDS
Neoplasms - venous thrombosis - deep vein thrombosis - pulmonary embolism - heparin - low-molecular-weight heparin - thromboembolism
REFERENCES
-
1
Trousseau A.
Phlegmasia alba dolens.
Clinique Medicale de l'Hotel-Dieu de Pais.
1865;
3
654-712
-
2
Prandoni P, Lensing A W, Piccioli A et al..
Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis.
Blood.
2002;
100
3484-3488
-
3
Hutten B A, Prins M H, Gent M, Ginsberg J, Tijssen J G, Buller H R.
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.
, [see comment]
J Clin Oncol.
2000;
18
3078-3083
-
4
Petralia G, Kakkar A K.
Antithrombotic therapy with low molecular weight heparin in cancer patients.
Eur J Med Res.
2004;
9
119-124
-
5
Buller H R, Agnelli G, Hull R D, Hyers T M, Prins M H, Raskob G E.
Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
Chest.
2004;
126(3 Suppl)
401S-428S
-
6
Hirsh J, Raschke R.
Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
Chest.
2004;
(3 Suppl)
188S-203S
-
7
Warkentin T E, Levine M N, Hirsh J et al..
Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.
N Engl J Med.
1995;
332
1330-1335
-
8
Gould M K, Dembitzer A D, Doyle R L, Hastie T J, Garber A M.
Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.
Ann Intern Med.
1999;
130
800-809
-
9
Dolovich L R, Ginsberg J S, Douketis J D, Holbrook A M, Cheah G.
A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency.
Arch Intern Med.
2000;
160
181-188
-
10
Shaughnessy S G, Young E, Deschamps P, Hirsh J.
The effects of low molecular weight and standard heparin on calcium loss from fetal rat calvaria.
Blood.
1995;
86
1368-1373
-
11
Muir J M, Hirsh J, Weitz J I, Andrew M, Young E, Shaughnessy S G.
A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats.
Blood.
1997;
89
3236-3242
-
12
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.
, [see comment]
N Engl J Med.
1996;
334
677-681
-
13
Koopman M M, 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. The Tasman Study Group.
, [see comment] [Erratum appears in N Engl J Med 1997;337:1251]
N Engl J Med.
1996;
334
682-687
-
14
Hull R D, Raskob G E, Pineo G F et al..
Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis.
, [see comment]
N Engl J Med.
1992;
326
975-982
-
15
Martins R, Colowick A, al Ewenstein B.
Anticoagulation in cancer patients with venous thromboembolic disease.
Blood.
1997;
909(Suppl 1)
297A
-
16
Bona R D, Sivjee K Y, Hickey A D, Wallace D M, Wajcs S B.
The efficacy and safety of oral anticoagulation in patients with cancer.
Thromb Haemost.
1995;
74
1055-1058
-
17
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: a randomized controlled study.
, [see comment]
Arch Intern Med.
2002;
162
1729-1735
-
18
Lee A Y, Levine M N, Baker R I et al..
Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.
, [see comment]
N Engl J Med.
2003;
349
146-153
-
19
Deitcher S, Kessler C, Merli G, Rigas J, Lyons R, Cort S.
Secondary prevention of venous thromboembolic events (VTE) in patients with active malignancy: a randomized study of enoxaparin sodium alone vs. initial enoxaparin sodium followed by warfarin for a 180-day period.
, [abstract]
J Thromb Haemost.
2003;
1(Suppl 1)
OC194
-
20
Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg J S.
Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis.
, [see comment]
Am J Med.
1996;
100
269-277
-
21
Hettiarachchi R J, Smorenburg S M, Ginsberg J, Levine M, Prins M H, Buller H R.
Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread.
Thromb Haemost.
1999;
82
947-952
-
22
Kakkar A KZ, Williamson R, Levine M, Low V, Lemoine N.
Low molecular weight heparin (LMWH) therapy and survival in advanced cancer.
Blood Coagul Fibrinolysis.
2002;
100
148A
-
23
Kakkar A K, Levine M N, Kadziola Z et al..
Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS).
J Clin Oncol.
2004;
22
1944-1948
-
24
Klerk C, Smorenburg S, Otten J, Büller H.
Malignancy and low-molecular weight-heparin therapy: the MALT trial.
, [abstract]
J Thromb Haemost.
2003;
1(Suppl 1)
OC195
-
25
Lee A Y, Rickles F R, Julian J A et al..
Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.
J Clin Oncol.
2005;
23
2123-2129
-
26
Lebeau B, Chastang C, Brechot J M et al..
Subcutaneous heparin treatment increases survival in small cell lung cancer. “Petites Cellules” Group.
Cancer.
1994;
74
38-45
-
27
Altinbas M, Coskun H S, Er O et al..
A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer.
J Thromb Haemost.
2004;
2
1266-1271
Dr. Gloria A Petralia
Centre for Surgical Science, Barts and The London Queen Mary's School of Medicine and Dentistry
Old Anatomy Building, Charterhouse Square, London EC1M 6BQ, United Kingdom
Email: petralia@tri-london.ac.uk