Despite the availability of safe and efficacious antithrombotic agents, as well as the vast clinical experience justifying their use, thromboembolism remains a frequent complication among cancer patients, with substantial adverse health and economic consequences.
Cancer-associated thrombosis remains an important negative predictor of survival as well as a leading cause of death, and is associated with higher (2- to 3-fold) thromboembolism recurrence rates, higher (2- to 6-fold) bleeding complications on anticoagulant therapy, increased hospitalisation and impaired quality of life.
Moreover, an incident thromboembolic event, once a cancer has been diagnosed and treatment started, often denotes a significant clinical hurdle, not only related to the morbidity and mortality associated to the thromboembolic event, but also the potential detrimental effect of an interruption or modification in therapy, attributable to the event and/or delivery of therapeutic anticoagulation.
Appropriate risk-adapted primary thromboprophylaxis can have a substantial impact not only on reduction of thromboembolism, but also disease response, survival, quality of life and healthcare resources.
Surgical intervention at any given site, for any malignancy, is associated with a high thromboembolic risk, in particular major abdominopelvic surgery for colorectal cancer. Thromboembolism remains an important and preventable complication of cancer surgery.
Overview of evidence (non-systematic literature review)[edit source]
No systematic reviews were undertaken for this topic. Practice points were based on selected published evidence. See Guidelines development process.
Pharmacological thromboprophylaxis can reduce the rates of thromboembolism in up to 80% of high risk surgical patients and therefore should be considered for all patients with colorectal cancer undergoing major surgery, unless contraindicated. The use of in-hospital thromboprophylaxis strategies, including low molecular-weight heparin or unfractionated heparin, in conjunction with graduated compression stockings and intermittent pneumatic compression, has been demonstrated to significantly reduce in-hospital rates of thromboembolism. Two recent Australian studies have demonstrated that with good compliance to thromboembolic prophylaxis guidelines, the clinically diagnosed thromboembolism rate is very low in Australia with a 0.79% in-hospital venous thromboembolism (VTE) rate and an out of hospital VTE rate of 0.39% in the first 28 days in one study, and a 4% 90 day VTE rate in a second study.
There are data suggesting that the risk of thromboembolism extends beyond the in-hospital stay after major abdominopelvic surgery. A Cochrane review analysing data from four Scandinavian studies published in 2009, suggested a 60% reduction in venography detected thromboembolism rates in patients undergoing abdominal or pelvic surgery who received extended prophylaxis compared to standard prophylaxis. The symptomatic thromboembolism rate was also significantly reduced, from 0.7% in the standard group to 0.2 % in the extended prophylaxis group. Given this finding, recent expert guidelines have suggested extended prophylaxis for 28 days post surgery should be considered, particularly in high-risk patients.. High-risk patients include patients aged over 60 years, those with operation times longer than two hours, patients with reduced mobility post procedure, and those with a past history of thromboembolism. The UK National Institute for Health and Care Excellence Guidelines go further and recommend extended prophylaxis for all patients having major cancer surgery in the abdomen and pelvis. None of these guidelines are specific to colorectal cancer patients.
One RCT (the PROLAPS study) evaluated extended VTE prophylaxis in colorectal cancer patients undergoing laparoscopic surgery, the trial. PROLAPS randomised 225 patients to either short or extended prophylaxis with a composite primary outcome measure combining clinical VTE and ultrasound-detected VTE 1 month postoperatively. It reported a significantly lower rate of VTE in the extended group compared with the standard group at 3 months (0.9% versus 9.7%, p = 0.005). However, there was no difference in the clinically detected rate of VTE.
Four more RCTs have compared standard in hospital and extended VTE prophylaxis and included colorectal cancer patients, but also included patients with other conditions. The ENOXACAN II and FAME trials showed a reduced rate of VTE in the extended groups but, as with the PROLAPS trial, there was no difference in the rate of clinically detected VTE. The CANBESURE triall and a Danish RCT were unable to detect any difference in VTE rate between standard and extended prophylaxis.
Given these findings, a clinical review of major clinical guidelines and published clinical data evaluating extended venous thromboprophylaxis after elective colorectal cancer surgery suggested that routine extended VTE prophylaxis should not be standard practice, and that it should be reserved for high risk patients.
- Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb Haemost 2016 Nov 24 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27882374.
- Walker AJ, Card TR, West J, Crooks C, Grainge MJ. Incidence of venous thromboembolism in patients with cancer - a cohort study using linked United Kingdom databases. Eur J Cancer 2013 Apr;49(6):1404-13 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23146958.
- Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H, et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 2006 Mar 1;24(7):1112-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16505431.
- Devani K, Patil N, Simons-Linares CR, Patel N, Jaiswal P, Patel P, et al. Trends in Hospitalization and Mortality of Venous Thromboembolism in Hospitalized Patients With Colon Cancer and Their Outcomes: US Perspective. Clin Colorectal Cancer 2016 Sep 20 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27777043.
- Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby G, Reddy DJ, et al. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism. Cochrane Database Syst Rev 2016 Sep 7;9:CD005258 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27600864.
- Bergqvist D. Venous thromboembolism: a review of risk and prevention in colorectal surgery patients. Dis Colon Rectum 2006 Oct;49(10):1620-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17019655.
- Nelson DW, Simianu VV, Bastawrous AL, Billingham RP, Fichera A, Florence MG, et al. Thromboembolic Complications and Prophylaxis Patterns in Colorectal Surgery. JAMA Surg 2015 Aug;150(8):712-20 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26060977.
- Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988 May 5;318(18):1162-73 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3283548.
- Barbui T, Cassinelli G, Cortelazzo S. Comparison of low molecular weight heparin cy 216 and unfractionated heparin in preventing post operative venous thromboembolism in general surgery a preliminary results of a cooperative study. Fibrinolysis Proteolysis 1990;4(79).
- Boneu B. An international multicentre study: Clivarin in the prevention of venous thromboembolism in patients undergoing general surgery. Report of the International Clivarin Assessment Group. Blood Coagul Fibrinolysis 1993 Dec;4 Suppl 1:S21-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8180325.
- Creperio G, Marabini M, Ciocia G, Bergonzi M, Fincato M. [Evaluation of the effectiveness and safety of Fragmin (Kabi 2165) versus calcium heparin in the prevention of deep venous thrombosis in general surgery]. Minerva Chir 1990 Sep 15;45(17):1101-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2177861.
- Kakkar VV, Murray WJ. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: a co-operative study. Br J Surg 1985 Oct;72(10):786-91 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3899240.
- Limmer J, Ellbrück D, Müller H, Eisele E, Rist J, Schütze F, et al. Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis. Clin Investig 1994 Nov;72(11):913-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7894222.
- McLeod RS, Geerts WH, Sniderman KW, Greenwood C, Gregoire RC, Taylor BM, et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg 2001 Mar;233(3):438-44 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11224634.
- Nurmohamed MT, Verhaeghe R, Haas S, Iriarte JA, Vogel G, van Rij AM, et al. A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 1995 Jun;169(6):567-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/7771617.
- Samama M, Bernard P, Bonnardot JP, Combe-Tamzali S, Lanson Y, Tissot E. Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. Br J Surg 1988 Feb;75(2):128-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2832030.
- Allan A, Williams JT, Bolton JP, Le Quesne LP. The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis. Br J Surg 1983;70: 172-4.
- Holford, CP. Graded compression for preventing deep venous thrombosis. Br Med J 1976;2, p. 969-70.
- Mellbring G, Palmér K. Prophylaxis of deep vein thrombosis after major abdominal surgery. Comparison between dihydroergotamine-heparin and intermittent pneumatic calf compression and evaluation of added graduated static compression. Acta Chir Scand 1986 Oct;152:597-600 Available from: http://www.ncbi.nlm.nih.gov/pubmed/3544626.
- Scurr JH, Coleridge-Smith PD, Hasty JH. Regimen for improved effectiveness of intermittent pneumatic compression in deep venous thrombosis prophylaxis. Surgery 1987;102, p. 816-20.
- Wille-Jørgensen P, Thorup J, Fischer A, Holst-Christensen J, Flamsholt R. Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: a randomized trial. Br J Surg 1985 Jul;72(7):579-81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/4016545.
- Wille-Jørgensen P, Hauch O, Dimo B, Christensen SW, Jensen R, Hansen B. Prophylaxis of deep venous thrombosis after acute abdominal operation. Surg Gynecol Obstet 1991 Jan;172(1):44-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/1702235.
- Bergqvist D, Lindblad B. The thromboprophylactic effect of graded elastic compression stockings in combination with dextran 70. Arch Surg 1984 Nov;119(11):1329-31 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6208877.
- Inada K, Shirai N, Hayashi M, Matsumoto K, Hirose M. Postoperative deep venous thrombosis in Japan. Incidence and prophylaxis. Am J Surg 1983 Jun;145(6):775-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6859416.
- Rasmussen A, Hansen PT, Lindholt J, Poulsen TD, Toftdahl DB, Gram J, et al. Venous thrombosis after abdominal surgery. A comparison between subcutaneous heparin and antithrombotic stockings, or both. J Med 1988;19(3-4):193-201 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2972790.
- Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectal surgery. Cochrane Database Syst Rev 2003;(4):CD001217 Available from: http://www.ncbi.nlm.nih.gov/pubmed/14583929.
- Chandra R, Melino G, Thomas M, Lawrence MJ, Hunter RA, Moore J. Is extended thromboprophylaxis necessary in elective colorectal cancer surgery? ANZ J Surg 2013 Dec;83(12):968-72 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23802729.
- Holwell A, McKenzie JL, Holmes M, Woods R, Nandurkar H, Tam CS, et al. Venous thromboembolism prevention in patients undergoing colorectal surgery for cancer. ANZ J Surg 2014 Apr;84(4):284-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23782713.
- Rasmussen MS, Jørgensen LN, Wille-Jørgensen P. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev 2009 Jan 21;(1):CD004318 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19160234.
- Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012 Feb;141(2 Suppl):e278S-325S Available from: http://www.ncbi.nlm.nih.gov/pubmed/22315265.
- Lyman GH, Bohlke K, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 2015 Feb 20;33(6):654-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25605844.
- National Comprehensive Cancer Network. Cancer-associated Venous Thromboembolic Disease. Washington2014.. Cancer-associated venous thromboembolic disease. Washington: NCCN.org; 2014 [cited 2016 Dec 16] Available from: http://williams.medicine.wisc.edu/vtecancer.pdf.
- Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012 Feb;141(2 Suppl):e227S-77S Available from: http://www.ncbi.nlm.nih.gov/pubmed/22315263.
- National Institute for Health and Care Excellence (NICE). Venous thromboembolism: reducing the risk. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. London, UK: Royal College of Physicians; 2010 Available from: https://www.ncbi.nlm.nih.gov/pubmed/23346611.
- Vedovati MC, Becattini C, Rondelli F, Boncompagni M, Camporese G, Balzarotti R, et al. A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Ann Surg 2014 Apr;259(4):665-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24253138.
- Pai A, Hurtuk MG, Park JJ, Marecik SJ, Prasad LM. A Randomized Study on 1-Week Versus 4-Week Prophylaxis for Venous Thromboembolism After Laparoscopic Surgery for Colorectal Cancer. Ann Surg 2016 Apr;263(4):e62 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25211266.
- Rasmussen MS, Jorgensen LN, Wille-Jørgensen P, Nielsen JD, Horn A, Mohn AC, et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 2006 Nov;4(11):2384-90 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16881934.
- Kakkar VV, Balibrea JL, Martínez-González J, Prandoni P, CANBESURE Study Group.. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. J Thromb Haemost 2010 Jun;8(6):1223-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20456751.
- Lausen I, Jensen R, Jorgensen LN, Rasmussen MS, Lyng KM, Andersen M, et al. Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis. Eur J Surg 1998 Sep;164(9):657-63 Available from: http://www.ncbi.nlm.nih.gov/pubmed/9728784.
- Sammour T, Chandra R, Moore JW. Extended venous thromboembolism prophylaxis after colorectal cancer surgery: the current state of the evidence. J Thromb Thrombolysis 2016 Jul;42(1):27-32 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26590997.