Thromboembolic prophylaxis

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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.[1]

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.[2]

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.[3][4]

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.[5]

Surgical intervention at any given site, for any malignancy, is associated with a high thromboembolic risk, in particular major abdominopelvic surgery for colorectal cancer.[6] ThromboembolismThe obstruction of a blood vessel by a blood clot that has become dislodged from another site. remains an important and preventable complication of cancer surgery.

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Overview of evidence (non-systematic literature review)

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.[7] 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.[5][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Two recent Australian studies[27][28] 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[27] in one study, and a 4% 90 day VTE rate in a second study[28].

There are data suggesting that the risk of thromboembolism extends beyond the in-hospital stay after major abdominopelvic surgery. A Cochrane review[29] 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.[29] Given this finding, recent expert guidelines have suggested extended prophylaxis for 28 days post surgery should be considered, particularly in high-risk patients.[30][31][32][33]. 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.[34] None of these guidelines are specific to colorectal cancer patients.

One RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. (the PROLAPS study) evaluated extended VTE prophylaxis in colorectal cancer patients undergoing laparoscopic surgery, the trial.[35] 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.[35] 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[36][37] but, as with the PROLAPS trial, there was no difference in the rate of clinically detected VTE. The CANBESURE triall[38] and a Danish RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.[39] 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.[40]
Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

All patients undergoing surgery for colorectal cancer should have standard thromboprophylaxis in hospital with compression stockings, unfractionated or low molecular-weight heparin and sequential compression devices. Extended prophylaxis for 28 days can be considered in high risk patients following colorectal cancer surgery.

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