4.1 Risk of VTE

Patients undergoing major (e.g. duration over 30 minutes) general or gynaecological surgery, who are aged 40 years or over, or who have other risk factors (see Table 1) have a significant risk of both asymptomatic and symptomatic VTE. The risk of VTE increases with the number of risk factors.

In the absence of specific thromboprophylaxis, the average risk of VTE endpoints in observational studies of such patients is as follows (see Tables 3 and 5):^{1,2,3,19,20,30,110}

In many of these studies patients were screened for asymptomatic DVT (using radiolabelled fibrinogen scanning or venography) and some patients with asymptomatic DVT were treated with full-dose anticoagulants, resulting in an under-estimate of the incidences of proximal DVT and of PE.

Most trials of antithrombotic prophylaxis in surgical patients have been performed in general (mainly abdominal) and gynaecological surgery.^{1,3,19,20,30,110}

4.2 Heparins

4.2.1 UNFRACTIONATED HEPARIN

In patients undergoing major surgery, meta-analyses of controlled trials,^2,110 have shown that subcutaneous low-dose UFH (5,000 IU, 8-12 hourly) is effective in reducing the risks of DVT and PE, as well as mortality (Table 5). The large International Multicentre Trial also observed reductions in the need for full-dose anticoagulant treatment for symptomatic DVT or PE.³⁰ Evidence level 1++

Adverse effects include an increase in the risk of wound haematomas (from 3.8% to 6.2%, see Table 5).¹ However, this can be minimised by avoiding subcutaneous injection near to wounds.

4.2.2 LOW MOLECULAR WEIGHT HEPARINS

Due to the ethical problems of using untreated control groups in trials after the demonstration that UFH was effective in reducing PE and mortality,^2,110 most studies of LMWH have used UFH as the control intervention. Two meta-analyses, published since the previous version of this guideline, concluded that there is no difference between LMWH and UFH in efficacy for thromboprophylaxis against DVT or PE in general surgery, nor is there any difference in increased risk of bleeding^98,99 (see Table 5). Evidence level 1++

An RCT reported only in abstract¹¹¹ also found no difference in the rate of fatal PE or bleeding when comparing a LMWH with UFH in 23,078 patients undergoing general or orthopaedic surgery.

LMWHs have two advantages over UFH^94,112

(1) they can be administered once daily (saving staff time)

(2) they are less likely to cause heparin-associated thrombocytopenia.

LMWHs are more expensive than UFH. Certoparin, dalteparin, enoxaparin, reviparin and tinzaparin are currently licensed for DVT prophylaxis in non-orthopaedic surgery.⁹⁴ Their relative efficacy has recently been reviewed.⁹⁷

The preferred methods of prophylaxis (because they reduce mortality as well as fatal PE) in patients undergoing major general or gynaecological surgery who are at significant risk of VTE are: subcutaneous low-dose UFH (5,000 IU, 8-12 hourly) or subcutaneous LMWH (dose as per manufacturer's instructions).

4.3 Mechanical methods

4.3.1 GRADUATED ELASTIC COMPRESSION STOCKINGS

Above-knee GECS appear similarly effective to UFH or LMWH in prophylaxis of asymptomatic DVT in patients undergoing general or gynaecological surgery (see section 3.2.1). They may also reduce the risk of symptomatic PE, but this awaits confirmation. Their effect on mortality is unknown. Evidence level 1+

In patients undergoing major general or gynaecological surgery GECS can be substituted for UFH or LMWH when these agents are contraindicated.

In patients undergoing general or gynaecological surgery the addition of above-knee GECS to UFH or LMWH increases the efficacy of prophylaxis against asymptomatic DVT (see section 3.2.1).⁷² The addition of GECS to UFH or LMWH should therefore be considered in patients at a significantly increased risk of VTE, e.g. in patients with multiple risk factors such as cancer. Evidence level 1++

GECS can be combined with UFH or LMWH in patients undergoing general or gynaecological surgery who are at high risk due to the presence of multiple risk factors.

4.3.2 INTERMITTENT PNEUMATIC COMPRESSION

There is evidence that IPC is as effective as UFH or LMWH in prophylaxis of asymptomatic DVT.¹⁹ IPC also reduces the risk of PE in cardiac surgery.⁸³ Evidence level 1+

When IPC is discontinued mechanical prophylaxis is usually continued with GECS.

In patients undergoing major general or gynaecological surgery, IPC followed by above-knee GECS can be substituted for UFH or LMWH when these agents are contraindicated.

4.4 Antiplatelet drugs (Aspirin)

Antiplatelet therapy is less effective than other agents in prophylaxis of asymptomatic DVT after major general or gynaecological surgery (risk reduction 37%), although a meta-analysis suggested that it may be similarly effective in prevention of PE (risk reduction 71%, see Table 3).^3,4 This is confirmed by the PEP study in orthopaedic patients.³¹ There is no evidence for a reduction in total mortality with aspirin, which increased the risk of bleeding (usually wound haematoma) from 5.6% to 7.8% (Table 3). Oral (or nasogastric or rectal) antiplatelet agents may not be practical immediately prior to general or gynaecological surgery. For these reasons, antiplatelet agents should be reserved for patients in whom UFH or LMWH are contraindicated. Evidence level 1++

Aspirin (150 mg/day orally, rectally or by nasogastric tube) is an alternative to UFH or LMWH when these agents are contraindicated in patients undergoing major general or gynaecological surgery who are at significant risk of VTE.

Although no studies of combined prophylaxis were identified, in view of the limited efficacy of aspirin in prevention of asymptomatic DVT, its combination with IPC/GECS may be logical in patients in whom UFH or LMWH are contraindicated.

There is some evidence to suggest that the combination of antiplatelet drugs with UFH or LMWH may be more effective in prophylaxis of PE than either agent alone^2,3,31 but the combination may also increase the risk of bleeding. Since the combined use of aspirin and heparin is not yet supported by reliable evidence, the balance of risk and benefit remains unclear. As discussed in section 3.3.3, perioperative low dose heparin is not contraindicated in patients already taking aspirin.

4.5 Dextrans

Intravenous dextran 40 or 70 is less effective than other agents in prophylaxis of asymptomatic DVT after major general or gynaecological surgery, but may be similarly effective in prevention of PE (see section 3.9). It also carries a risk of allergic reactions and anaphylaxis. It may be considered as alternative prophylaxis of VTE in patients undergoing major general or gynaecological surgery who are at high risk.¹⁹ Evidence level 1+

Intravenous dextran 40 or 70 is a possible alternative prophylaxis of VTE in high risk patients undergoing major general or gynaecological surgery.

4.6 Oral anticoagulants

Warfarin is rarely used for prophylaxis of postoperative VTE due to the increased risk of bleeding and need for regular monitoring.

In patients who are on long term oral anticoagulant therapy (e.g. for atrial fibrillation or heart valve disease/prosthesis) and who are immobilised by illness, trauma or surgery, continuation of oral anticoagulants may be appropriate prophylaxis (see section 3.8). Evidence level 4