Download PDF
Hamostaseologie 2012; 32(02): 132-137
DOI: 10.5482/ha-1173
Review
Schattauer GmbH

Risk of venous thromboembolism and primary prophylaxis in cancer

Should all patients receive thromboprophylaxis?Risiko für venöse Thromboembolien und Primärprophylaxe bei KrebsSollten alle Patienten eine Thromboseprophylaxe erhalten?
I. Pabinger
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
,
C. Ay
1   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Austria
› Author Affiliations
Further Information

Publication History

received: 21 July 2011

accepted: 21 July 2011

Publication Date:
28 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Venous thromboembolism (VTE) is a common complication in patients with cancer that causes significant morbidity and mortality. Several patient-, tumour-and treatment-related risk factors for VTE in cancer patients have been identified. An effective and safe thromboprophylaxis in cancer patients at high risk of VTE is desirable. Recently, the identification of potential biomarkers and the development of risk scoring models for prediction of cancer-associated VTE have been published. Whether primary VTE prophylaxis based on risk assessment through these biomarkers and risk prediction models might be useful, is currently not yet known. However, thromboprophylaxis is clearly indicated in high-risk situations. While VTE prophylaxis is recommended in cancer patients undergoing surgery and in hospitalised patients with acute disease, studies in ambulatory cancer patients are still rare and evidence for primary VTE prophylaxis is currently limited. In this review, risk factors associated with VTE in cancer patients and current approaches of thromboprophylaxis in different settings, specifically in ambulatory cancer patients are subjected to a critical evaluation.

Zusammenfassung

Die venöse Thromboembolie (VTE) ist eine häufige Komplikation bei Krebspatienten mit erheblicher Morbidität und Mortalität. Verschiedene patienten-, tumor-und behandlungsbezogene Risikofaktoren für VTE bei Krebspatienten sind bekannt. Eine wirksame und sichere Thromboseprophylaxe für Krebspatienten mit einem hohen VTE-Risiko ist wünschenswert. Die Identifizierung potenzieller Biomarker und die Entwicklung eines Risikovorhersage-Modells für krebsassoziierte VTE wurden kürzlich publiziert. In wie weit eine primäre VTE-Prophylaxe auf Grundlage der Risikobeurteilung mit Hilfe dieser Biomarker und Risikovorhersage-Modelle vorteilhaft sein kann, ist zurzeit nicht bekannt. In Hochrisikosituationen jedoch ist die Thromboseprophylaxe klar indiziert. Während bei chirurgisch behandelten Krebspatienten und bei stationären Patienten mit akuten Krankheiten eine VTE-Prophylaxe empfohlen wird, liegen kaum Studien mit ambulanten Krebspatienten vor und die Datenlage für eine primäre VTE-Prophylaxe ist momentan beschränkt.

In dieser Übersicht werden Risikofaktoren für VTE bei Krebspatienten und aktuelle Ansätze zur Thromboseprophylaxe, besonders bei ambulanten Krebspatienten, einer kritischen Beurteilung unterzogen.

Keywords

Cancer - venous thromboembolism - thromboprophylaxis

Schlüsselwörter

Krebs - venöse Thromboembolie - Thromboseprophylaxe
 

  • References

  • 1 Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation 2003; 107: I17-I21.
    CrossrefPubMedGoogle Scholar
  • 2 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
    CrossrefPubMedGoogle Scholar
  • 3 Ay C, Simanek R, Vormittag R. et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 2008; 112: 2703-2708.
    CrossrefPubMedGoogle Scholar
  • 4 Kawaguchi T, Kumabe T, Kanamori M. et al. Early detection of venous thromboembolism in patients with neuroepithelial tumor: efficacy of screening with serum D-dimer measurements and Doppler ultrasonography. J Neurooncol 2011; 101: 495-504.
    CrossrefPubMedGoogle Scholar
  • 5 Beck-Razi N, Kuzmin A, Koren D. et al. Asymptomatic deep vein thrombosis in advanced cancer patients: the value of venous sonography. J Clin Ultrasound 2010; 38: 232-237.
    PubMedGoogle Scholar
  • 6 Satoh T, Oki A, Uno K. et al. High incidence of silent venous thromboembolism before treatment in ovarian cancer. Br J Cancer 2007; 97: 1053-1057.
    CrossrefPubMedGoogle Scholar
  • 7 Heidrich H, Konau E, Hesse P. Asymptomatic venous thrombosis in cancer patients--a problem often overlooked. Results of a retrospective and prospective study. Vasa 2009; 38: 160-166.
    CrossrefPubMedGoogle Scholar
  • 8 Sorensen HT, Mellemkjaer L, Olsen JH. et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343: 1846-1850.
    CrossrefPubMedGoogle Scholar
  • 9 Alcalay A, Wun T, Khatri V. et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 2006; 24: 1112-1118.
    CrossrefPubMedGoogle Scholar
  • 10 Lyman GH. Venous thromboembolism in the patient with cancer: focus on burden of disease and benefits of thromboprophylaxis. Cancer 2011; 117: 1334-1349.
    CrossrefPubMedGoogle Scholar
  • 11 Heit JA, Silverstein MD, Mohr DN. et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160: 809-815.
    CrossrefPubMedGoogle Scholar
  • 12 Khorana AA, Francis CW, Culakova E. et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007; 110: 2339-2346.
    CrossrefPubMedGoogle Scholar
  • 13 Ay C, Vormittag R, Dunkler D. et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2009; 27: 4124-4129.
    CrossrefPubMedGoogle Scholar
  • 14 Blom JW, Doggen CJ, Osanto S. et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293: 715-722.
    CrossrefPubMedGoogle Scholar
  • 15 Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002; 87: 575-579.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Chew HK, Wun T, Harvey D. et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166: 458-464.
    CrossrefPubMedGoogle Scholar
  • 17 Numico G, Garrone O, Dongiovanni V. et al. Prospective evaluation of major vascular events in patients with nonsmall cell lung carcinoma treated with cisplatin and gemcitabine. Cancer 2005; 103: 994-999.
    CrossrefPubMedGoogle Scholar
  • 18 Mandala M, Barni S, Prins M. et al. Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial. Ann Oncol 2010; 21: 871-876.
    CrossrefPubMedGoogle Scholar
  • 19 Simanek R, Vormittag R, Ay C. et al. High platelet count associated with venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). J Thromb Haemost 2010; 08: 114-120.
    CrossrefPubMedGoogle Scholar
  • 20 Sparsa A, Durox H, Doffoel-Hantz V. et al. High prevalence and risk factors of thromboembolism in stage IV melanoma. J Eur Acad Dermatol Venereol 2011; 25: 340-344.
    CrossrefPubMedGoogle Scholar
  • 21 Chew HK, Davies AM, Wun T. et al. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost 2008; 06: 601-608.
    CrossrefPubMedGoogle Scholar
  • 22 Blom JW, Vanderschoot JP, Oostindier MJ. et al. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 2006; 04: 529-535.
    CrossrefPubMedGoogle Scholar
  • 23 Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer 2010; 102 (Suppl. 01) S2-S9.
    CrossrefPubMedGoogle Scholar
  • 24 Zangari M, Anaissie E, Barlogie B. et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 2001; 98: 1614-1615.
    CrossrefPubMedGoogle Scholar
  • 25 Urbauer E, Kaufmann H, Nosslinger T. et al. Thromboembolic events during treatment with thalidomide. Blood 2002; 99: 4247-4248.
    CrossrefPubMedGoogle Scholar
  • 26 Falanga A, Marchetti M. Venous thromboembolism in the hematologic malignancies. J Clin Oncol 2009; 27: 4848-4857.
    CrossrefPubMedGoogle Scholar
  • 27 Nalluri SR, Chu D, Keresztes R. et al. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300: 2277-2285.
    CrossrefPubMedGoogle Scholar
  • 28 Hapani S, Sher A, Chu D. et al. Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis. Oncology 2010; 79: 27-38.
    CrossrefPubMedGoogle Scholar
  • 29 Kakkar AK. Prevention of venous thromboembolism in the cancer surgical patient. J Clin Oncol 2009; 27: 4881-4884.
    CrossrefPubMedGoogle Scholar
  • 30 Geerts WH, Bergqvist D, Pineo GF. et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th ed). Chest 2008; 133: 381S-453S.
    CrossrefPubMedGoogle Scholar
  • 31 Lyman GH, Khorana AA, Falanga A. et al. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25: 5490-5505.
    CrossrefPubMedGoogle Scholar
  • 32 Bottaro FJ, Elizondo MC, Doti C. et al. Efficacy of extended thromboprophylaxis in major abdominal surgery: what does the evidence show? A metaanalysis. Thromb Haemost 2008; 99: 1104-1111.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Akl EA, Terrenato I, Barba M. et al. Extended perioperative thromboprophylaxis in patients with cancer. A systematic review. Thromb Haemost 2008; 100: 1176-1180.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Khorana AA, Francis CW, Culakova E. et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005; 104: 2822-2829.
    CrossrefPubMedGoogle Scholar
  • 35 Kroger K, Weiland D, Ose C. et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 2006; 17: 297-303.
    CrossrefPubMedGoogle Scholar
  • 36 Kanz R, Vukovich T, Vormittag R. et al. Thrombosis risk and survival in cancer patients with elevated C-reactive protein. J Thromb Haemost 2011; 09: 57-63.
    CrossrefPubMedGoogle Scholar
  • 37 Ay C, Jungbauer LV, Sailer T. et al. High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant. Clin Chem 2007; 53: 1235-1243.
    CrossrefPubMedGoogle Scholar
  • 38 McEver RP. Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost 2001; 86: 746-756.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1983; 62: 14-31.
    PubMedGoogle Scholar
  • 40 Zurborn KH, Duscha H, Gram J. et al. Investigations of coagulation system and fibrinolysis in patients with disseminated adenocarcinomas and non-Hodgkin’s lymphomas. Oncology 1990; 47: 376-380.
    CrossrefPubMedGoogle Scholar
  • 41 Falanga A. Thrombophilia in cancer. Semin Thromb Hemost 2005; 31: 104-110.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-155.
    CrossrefPubMedGoogle Scholar
  • 43 Kyrle PA, Minar E, Hirschl M. et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000; 343: 457-462.
    CrossrefPubMedGoogle Scholar
  • 44 Vormittag R, Simanek R, Ay C. et al. High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 2009; 29: 2176-2181.
    CrossrefPubMedGoogle Scholar
  • 45 Thaler J, Ay C, Weinstabl H. et al. Circulating procoagulant microparticles in cancer patients. Ann Hematol 2011; 90: 447-453.
    CrossrefPubMedGoogle Scholar
  • 46 Hemker HC, Beguin S. Thrombin generation in plasma: its assessment via the endogenous thrombin potential. Thromb Haemost 1995; 74: 134-138.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Lutsey PL, Folsom AR, Heckbert SR. et al. Peak thrombin generation and subsequent venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE) study. J Thromb Haemost 2009; 07: 1639-1648.
    CrossrefPubMedGoogle Scholar
  • 48 Hron G, Kollars M, Binder BR. et al. Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation. JAMA 2006; 296: 397-402.
    CrossrefPubMedGoogle Scholar
  • 49 Ay C, Dunkler D, Simanek R. et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011; 29: 2099-2103.
    CrossrefPubMedGoogle Scholar
  • 50 Ay C, Dunkler D, Marosi C. et al. Prediction of venous thromboembolism in cancer patients. Blood. 116. 5377-5382.
    PubMedGoogle Scholar
  • 51 Levine M, Hirsh J, Gent M. et al. Double-blind randomised trial of a very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer. Lancet 1994; 343: 886-889.
    CrossrefPubMedGoogle Scholar
  • 52 Perry JR, Julian JA, Laperriere NJ. et al. PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma. J Thromb Haemost 2010; 08: 1959-1965.
    CrossrefPubMedGoogle Scholar
  • 53 Agnelli G, Gussoni G, Bianchini C. et al. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10: 943-949.
    CrossrefPubMedGoogle Scholar
  • 54 Riess H, Pelzer U, Hilbig A. et al. Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy. BMC Cancer 2008; 08: 361.
    CrossrefPubMedGoogle Scholar
  • 55 Riess A. et al. Data presented at the congress of the ISTH in Boston. 2009
    PubMedGoogle Scholar