Semin Thromb Hemost 2005; 31(1): 104-110
DOI: 10.1055/s-2005-863812
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Thrombophilia in Cancer

Anna Falanga1
  • 1Associate Professor, Hematology-Oncology Department, Ospedali Riuniti Bergamo, Bergamo, Italy
Further Information

Publication History

Publication Date:
11 February 2005 (online)

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.

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