ABSTRACT
Malignancy is an acquired thrombophilic condition associated with a significant risk
of thrombosis. Venous and arterial thromboembolism is a common complication for patients
with cancer, who also present with a hypercoagulable state, even in the absence of
manifest thrombosis. Furthermore, clotting activation may play a role in tumor progression.
The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role
is attributed to the tumor cell capacity to interact with and activate the host hemostatic
system. Among other factors, the prothrombotic action of antitumor therapies is also
important. Thrombotic events can influence the morbidity and mortality of the underlying
disease. Therefore, preventing these complications in cancer patients is a clinically
relevant issue. Recently, new approaches to the prevention and cure of thrombosis
in cancer have been investigated, and the hypothesis that strategies to inhibit clotting
mechanism may favorably affect malignant disease is gaining increasing interest. In
this article, the various aspects of the complex relationship between thrombosis and
cancer, from pathophysiology to therapy, are reviewed.
KEYWORDS
Cancer - thrombosis - hypercoagulability - tumor procoagulant property - chemotherapy
REFERENCES
- 1
Rickles F R, Levine M N.
Epidemiology of thrombosis in cancer.
Acta Haematol.
2001;
106
6-12
- 2
Donati M B.
Cancer and thrombosis: from phlegmasia alba dolens to transgenic mice.
Thromb Haemost.
1995;
74
278-281
- 3
Falanga A, Barbui T.
Coagulopathy of acute promyelocytic leukemia.
Acta Haematol.
2001;
106
43-51
- 4
Falanga A, Rickles F R.
Pathophysiology of the thrombophilic state in the cancer patients.
Semin Thromb Hemost.
1999;
25
173-182
- 5
Falanga A, Barbui T, Rickles F R et al..
Guidelines for clotting studies in cancer patients.
Thromb Haemost.
1993;
70
540-542
- 6
Falanga A, Marchetti M, Vignoli A et al..
Clotting mechanisms and cancer: implications in thrombus formation and tumor progression.
Clin Adv Hematol Oncol.
2003;
1
673-678
- 7
Edwards R L, Rickles F R, Moritz T E et al..
Abnormalities of blood coagulation tests in patients with cancer.
Am J Clin Pathol.
1987;
88
596-602
- 8
Falanga A, Ofosu F A, Cortelazzo S et al..
Preliminary study to identify cancer patients at high risk of venous thrombosis following
major surgery.
Br J Haematol.
1993;
85
745-750
- 9
Goldenberg N, Kahn S R, Solymoss S.
Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism.
J Clin Oncol.
2003;
21
4194-4199
- 10
Beer J H, Haeberli A, Vogt A et al..
Coagulation markers predict survival in cancer patients.
Thromb Haemost.
2002;
88
745-749
- 11
Prandoni P, Lensing A WA, Büller H R et al..
Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.
N Engl J Med.
1992;
327
1128-1133
- 12
Piccioli A, Lensing A W, Prins M H et al..
SOMIT Investigators Group. Extensive screening for occult malignant disease in idiopathic
venous thromboembolism: a prospective randomized clinical trial.
J Thromb Haemost.
2004;
2
884-889
- 13
Kakkar A K, Williamson R CN.
Prevention of venous thromboembolism in cancer patients.
Semin Thromb Hemost.
1999;
25
239-243
- 14
Gale A J, Gordon S.
Update on tumor cell procoagulant factors.
Acta Haematol.
2001;
106
25-32
- 15
Falanga A, Consonni R, Marchetti M et al..
Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic
acid (ATRA) in acute promyelocytic leukemia cells.
Blood.
1998;
92
143-151
- 16
Zacharski L R, Wojtukiewicz M Z, Costantini V, Ornstein D L, Memoli V A.
Pathways of coagulation/fibrinolysis activation in malignancy.
Semin Thromb Hemost.
1992;
18
104-106
- 17
Look M P, Van Putten W L, Duffy M J et al..
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its
inhibitor PAI-1 in 8377 breast cancer patients.
J Natl Cancer Inst.
2002;
94
116-128
- 18 Fernandez P M, Patierno S R, Rickles F R. Tumor angiogenesis and blood coagulation. In:
Lugassy G, Falanga A, Kakkar AK, Rickles FR Thrombosis and Cancer. London; Martin
Dunitz 2004: 69-98
- 19 Honn K V, Tang D G, Chen Y Q. Adhesion molecules and site-specific metastases. In:
Neri Seneri GG, Abbate R, Gensini, G, Prisco D Thrombosis: An Update Florence; Scientific
Press 1992: 269-303
- 20
Marchetti M, Falanga A, Giovanelli S et al..
All-trans-retinoic acid increases the adhesion to endothelium of the acute promyelocytic
leukemia cell line NB4.
Br J Haematol.
1996;
93
360-366
- 21
Levine M N, Gent M, Hirsh J et al..
The thrombogenic effect of anti-cancer drug therapy in women with stage II breast
cancer.
N Engl J Med.
1988;
318
404-407
- 22
Lee A Y, Levine M N.
The thrombophilic state induced by therapeutic agents in the cancer patients.
Semin Thromb Hemost.
1999;
25
137-145
- 23
Barbui T, Falanga A.
Thalidomide and thrombosis in multiple myeloma.
J Thromb Haemost.
2003;
1
421-422
- 24
Kuenen B C, Levi M, Meijers J CM et al..
Analysis of coagulation cascade and endothelial cell activation during inhibition
of vascular endothelial growth factor/vascular endothelial growth factor receptor
pathway in cancer patients.
Arterioscler Thromb Vasc Biol.
2002;
22
1500-1505
- 25
Bergqvist D, Agnelli G, Cohen A T et al..
Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery
for cancer.
N Engl J Med.
2002;
346
975-980
- 26
Falanga A.
Thrombosis and malignancy: an underestimated problem.
Haematologica.
2003;
88
607-610
- 27 Levine M. Prevention of cancer-associated thrombosis: an overview. In: Lugassy
G, Falanga A, Kakkar AK, Rickles FR Thrombosis and Cancer London; Martin Dunitz 2004:
151-161
- 28
Levine M N, Gent M, Hirsh J et al..
Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism
in stage IV breast cancer.
Lancet.
1994;
343
886-889
- 29
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
- 30
Lee A YY, Levine M N, Baker R I et al..
for the CLOT Investigators.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
- 31
Verso M, Agnelli G.
Venous thromboembolism associated with long-term use of central venous catheters in
cancer patients.
J Clin Oncol.
2003;
21
3665-3675
- 32 Breddin H K, Bauersachs R. Prevention and treatment of thrombosis in cancer patients. In:
Lugassy G, Falanga A, Kakkar AK, Rickles FR Thrombosis and Cancer London; Martin Dunitz
2004: 187-206
- 33
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
- 34
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
- 35
Falanga A.
The effect of anticoagulant drugs on cancer.
J Thromb Haemost.
2004;
2
1263-1265
Anna FalangaM.D.
Hematology-Oncology Department, Ospedali Riuniti Bergamo
Largo Barozzi 1, 24128 Bergamo, Italy
eMail: annafalanga@yahoo.com