Download PDF
Semin Thromb Hemost 2006; 32(7): 694-699
DOI: 10.1055/s-2006-951297
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Cancer and Venous Thromboembolism

Andrea Piccioli1 , Anna Falanga2 , Ugo Baccaglini3 , Marina Marchetti2 , Paolo Prandoni1
  • 1Department of Medical and Surgical Sciences, University of Padua, Italy
  • 2Division of Hematology, Department of Hematology-Oncology, Ospedali Riuniti di Bergamo, Bergamo, Italy
  • 3Department of Day Surgery, University of Padua, Italy
Further Information

Publication History

Publication Date:
06 October 2006 (online)

    Permissions and Reprints

ABSTRACT

The evidence of the important two-way clinical correlation between cancer and venous thromboembolism (VTE) dates back to Trousseau's time. Over time it has been established that cancer patients not only exhibit a higher risk of developing VTE when compared with noncancer patients, but also that VTE, especially in its idiopathic presentation, sometimes acts as an epiphenomenon of a hidden cancer, offering possible chances for anticipated diagnosis of the pathology. Research has contributed greatly to the progression of this field through the identification of VTE risk factors in this setting, and through the assessment of the most adequate thromboprophylaxis and treatment modalities as well as secondary prophylaxis management. Anticoagulant drugs appear to be an attractive strategy in cancer treatment because there is growing evidence for their possible benefits in terms of cancer prognosis and patient survival.

KEYWORDS

Cancer - venous thromboembolism - low molecular weight heparin - warfarin - hypercoagulability

REFERENCES

  • 1 Trousseau A. Phlegmasia alba dolens. In: Clinique Medical de l'Hotel Dieu de Paris. London; The New Sydenham Society 1865: 94-96
    Google Scholar
  • 2 Prandoni P, Falanga A, Piccioli A. Cancer and venous thromboembolism.  Lancet Oncol. 2005;  6 401-410
    CrossrefPubMedGoogle Scholar
  • 3 Falanga A, Barbui T, Rickles F R, Levine M N. Guidelines for clotting studies in cancer patients.  Thromb Haemost. 1993;  70 540-542
    PubMedGoogle Scholar
  • 4 Falanga A, Donati M B. Pathogenesis of thrombosis in patients with malignancy.  Int J Hematol. 2001;  73 137-144
    CrossrefPubMedGoogle Scholar
  • 5 Gale A J, Gordon S G. Update on tumor cell procoagulant factors.  Acta Haematol. 2001;  106 25-32
    CrossrefPubMedGoogle Scholar
  • 6 Otten H M, Prins M H. Venous thromboembolism and occult malignancy.  Thromb Res. 2001;  102 V187-V194
    CrossrefPubMedGoogle Scholar
  • 7 Blom J W, Doggen C J, Osanto S, Rosendaal F R. Malignancies, prothrombotic mutations, and the risk of venous thrombosis.  JAMA. 2005;  293 715-722
    CrossrefPubMedGoogle Scholar
  • 8 Piccioli A, Prandoni P, Ewenstein B M, Goldhaber S Z. Cancer and venous thromboembolism.  Am Heart J. 1996;  132 850-855
    CrossrefPubMedGoogle Scholar
  • 9 Shen V S, Pollak E W. Fatal pulmonary embolism in cancer patients: is heparin prophylaxis justified?.  South Med J. 1980;  73 841-843
    PubMedGoogle Scholar
  • 10 Prandoni P, Piccioli A, Girolami A. Cancer and venous thromboembolism: an overview.  Haematologica. 1999;  84 437-445
    PubMedGoogle Scholar
  • 11 Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary embolism after hospital discharge: an underestimated risk.  Arch Surg. 1992;  127 310-313
    CrossrefPubMedGoogle Scholar
  • 12 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
    CrossrefPubMedGoogle Scholar
  • 13 Levine M N. Prevention of thrombotic disorders in cancer patients undergoing chemotherapy.  Thromb Haemost. 1997;  78 133-136
    PubMedGoogle Scholar
  • 14 Goodnough L T, Saito A, Manni A et al.. Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five-drug chemotherapy regimen: a study of 159 patients.  Cancer. 1984;  54 1264-1268
    CrossrefPubMedGoogle Scholar
  • 15 Otten H MMB, Mathijssen J, ten Cate H et al.. Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon.  Arch Intern Med. 2004;  164 190-194
    CrossrefPubMedGoogle Scholar
  • 16 Prichard K I, Paterson A H, Paul N A et al.. Increased thromboembolic complications with concurrent tamoxifen and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer.  J Clin Oncol. 1996;  14 2731-2737
    CrossrefPubMedGoogle Scholar
  • 17 Deitcher S R, Gemes M PV. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma.  Cancer. 2004;  101 439-449
    CrossrefPubMedGoogle Scholar
  • 18 Goldhaber S Z. Tamoxifen: preventing breast cancer and placing the risk of deep vein thrombosis in perspective.  Circulation. 2005;  111 539-541
    CrossrefPubMedGoogle Scholar
  • 19 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
    CrossrefPubMedGoogle Scholar
  • 20 Bern M M, Lokich J J, Wallach S R et al.. Very low dose of warfarin can prevent thrombosis in central venous catheters: a prospective trial.  Ann Intern Med. 1990;  112 423-428
    CrossrefPubMedGoogle Scholar
  • 21 Monreal M, Alastrue A, Rull M et al.. Upper extremity deep vein thrombosis in cancer patients with venous access devices prophylaxis with a low molecular weight heparin (Fragmin).  Thromb Haemost. 1996;  75 251-253
    PubMedGoogle Scholar
  • 22 Levine M N, Lee A Y, Kakkar A K. From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer.  J Thromb Haemost. 2003;  1 1456-1463
    CrossrefPubMedGoogle Scholar
  • 23 Geerts W H, Pineo G F, Heith J A et al.. Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy.  Chest. 2004;  126 338S-400S
    CrossrefPubMedGoogle Scholar
  • 24 Bergqvist D, Burmark U S, Flordal P A et al.. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 anti Xa IU in 2070 patients.  Br J Surg. 1995;  82 496-501
    CrossrefPubMedGoogle Scholar
  • 25 Enoxacan Study Group . Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment.  Br J Surg. 1997;  84 1099-1103
    CrossrefPubMedGoogle Scholar
  • 26 Rasmussen M S, Jorgensen L N, Wille-Jorgensen J P et al.. Prolonged prophylaxis with low molecular weight heparin (Dalteparin) after major abdominal surgery: the FAME study. In: Programs and Abstracts of the XIX Congress of the International Society of Thrombosis and Haemostasis July 12-18, 2003 Birmingham, United Kingdom (abst);
    Google Scholar
  • 27 Nurmohamed M T, van Riel A M, Henkens C M et al.. Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery.  Thromb Haemost. 1996;  75 233-238
    PubMedGoogle Scholar
  • 28 Agnelli G, Piovella F, Buoncristiani P et al.. Enoxaparin plus compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery.  N Engl J Med. 1998;  339 80-85
    CrossrefPubMedGoogle Scholar
  • 29 Levine M, Hirsh J, Gent M et al.. Double-blind randomized trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer.  Lancet. 1994;  343 886-889
    CrossrefPubMedGoogle Scholar
  • 30 Büller H R, Agnelli G, Hull R D et al.. Antithrombotic therapy for venous thromboembolic disease: the seventh ACCP Conference on antithrombotic and thrombolytic therapy.  Chest. 2004;  126(suppl) 401S-428S
    CrossrefPubMedGoogle Scholar
  • 31 Prandoni P, Lensing A WA, Cogo A et al.. The long-term clinical coarse of acute deep vein thrombosis.  Ann Intern Med. 1996;  125 1-7
    CrossrefPubMedGoogle Scholar
  • 32 Heit J A, Mohr D N, Silverstein M D et al.. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study.  Arch Intern Med. 2000;  160 761-768
    CrossrefPubMedGoogle Scholar
  • 33 Prandoni P, Lensing A WA, Piccioli A et al.. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thromboembolism.  Blood. 2002;  100 3484-3488
    CrossrefPubMedGoogle Scholar
  • 34 Lee A Y, Levine M N, Baker R I et al.. Low-molecular-weight heparin versus a coumarin for the prevention of venous thromboembolism in patients with cancer.  N Engl J Med. 2003;  349 146-153
    CrossrefPubMedGoogle Scholar
  • 35 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.  Arch Intern Med. 2002;  162 1729-1735
    CrossrefPubMedGoogle Scholar
  • 36 Falanga A, Piccioli A. Effect of anticoagulant drugs in cancer.  Curr Opin Pulm Med. 2005;  11 403-407
    CrossrefPubMedGoogle Scholar
  • 37 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.  J Clin Oncol. 2004;  22 1944-1948
    CrossrefPubMedGoogle Scholar
  • 38 Klerk C PW, Smorenburg S M, Otten H YM et al.. The effect of low-molecular-weight heparin on survival in patients with advanced malignancy.  J Clin Oncol. 2005;  23 2130-2135
    CrossrefPubMedGoogle Scholar
  • 39 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
    CrossrefPubMedGoogle Scholar
  • 40 Sorensen H T, Mellemkjaer L, Steffensen H et al.. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism.  N Engl J Med. 1998;  338 1169-1173
    CrossrefPubMedGoogle Scholar
  • 41 Baron J A, Gridley G, Weiderpass E et al.. Venous thromboembolism and cancer.  Lancet. 1998;  351 1077-1080
    CrossrefPubMedGoogle Scholar
  • 42 Murchison J T, Wylie L, Stockton D L. Excess risk of cancer in patients with primary venous thromboembolism: a national population-based cohort study.  Br J Cancer. 2004;  91 92-95
    CrossrefPubMedGoogle Scholar
  • 43 White R H, Chew H K, Zhou H et al.. Incidence of venous thromboembolism in the year before the diagnosis of cancer in 528,693 adults.  Arch Inter Med. 2005;  65 1782-1787
    PubMedGoogle Scholar
  • 44 Sorensen H T, Mellemkjare L, Olsen J H, Baron J A. Prognosis of cancers associated with venous thromboembolism.  N Engl J Med. 2000;  343 1846-1850
    CrossrefPubMedGoogle Scholar
  • 45 Monreal M, Lensing A WA, Prins M H et al.. Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism.  J Thromb Haemost. 2004;  2 876-881
    CrossrefPubMedGoogle Scholar
  • 46 Piccioli A, Lensing A WA, Prins M H et al.. Extensive screening for occult malignant disease in idiopathic venous thromboembolism.  J Thromb Haemost. 2004;  2 884-889
    CrossrefPubMedGoogle Scholar

Andrea PiccioliM.D. 

Department of Medical and Surgical Sciences, 2nd Chair of Internal Medicine, University of Padua

Via Ospedale Civile 105, 35128 Padua, Italy

Email: andreapiccioli@libero.it

      >