Thromoboprophylaxis for highrisk surgical patients Major orthopaedic surgery

In the absence of prophylaxis, patients undergoing elective THR have a 2 to 5% incidence of symptomatic VTE and 0.1 to 2% fatal PE. Asymptomatic DVT, however, is found in 42 to 57%.93,94 Primary prophylaxis is the only effective method of reducing VTE in this population. Non-invasive screening techniques on discharge or venography are unacceptable alternatives.105

Non-pharmacological methods of prophylaxis

Physical methods of prophylaxis are designed to reduce stasis in the leg veins. Three types have been evaluated: graduated compression stockings (GCSS), intermittent pneumatic compression (IPC) devices, and venous foot pump (VFP). These methods are not associated with increased perioperative bleeding, but their problem is low compliance. Overall experience is also very limited in contrast with the pharmacological agents. These methods, unlike pharmacological agents, have not been shown to reduce mortality or PE and, therefore, appear to be less effective than pharmacological methods. In addition, GCSs are contraindicated in patients with peripheral vascular disease.

All three methods have been evaluated in patients undergoing THR, GCSs,95 IPC,96--101 and VFP.102 103 There is no evidence that GCSs are effective. In two studies, IPC devices were as effective as warfarin.97--99 In another study, IPC was less effective than warfarin in preventing proximal DVT.100 In another randomised study, IPC of the calf and the thigh produced a 50% reduction in both distal and proximal DVT.98 VFP is also effective.102,103

Pharmacological prophylaxis

Six different classes of anti-thrombotic agents have been evaluated in patients undergoing major orthopaedic surgery. These include low dose UFH, LMWH, aspirin, vitamin K antagonists, fondaparinux, and ximelagatran.

Aspirin was ineffective in reducing symptomatic VTE in the Pulmonary Embolism Prevention (PEP) Trial of 4088 patients undergoing THR or TKA.104 Vitamin K antagonists and LMWH are effective and fairly common modalities in prophylaxis in this setting. LMWH is more effective than vitamin K antagonists and low dose UFH.105--111 Recent evidence, however, suggests that fondaparinux is more effective than LMWH.112

Anderson et al. compared the relative efficacy of LMWH with that of UFH in six well-conducted trials for DVT prevention after THR.106 LMWH was found to be significantly more effective than UFH in preventing DVT, as shown by venography, after total hip replacement. Meta-analysis has confirmed that the benefit of LMWH over UFH was only demonstrable for the prevention of proximal-vein thrombosis, while the rates of calf-vein thrombosis were similar in the two groups. The haemorrhagic risk was not significantly different between the two groups. Furthermore, the superiority of LMWH over oral anticoagulants has emerged in almost all single trials dealing with this

113--115 issue. 115

In a recent, large, open-label trial THR patients were randomly assigned to in-hospital prophylaxis with either LMWH (enoxaparin, 30 mg x 2) or adjusted-dose warfarin.113 Symptomatic, objectively documented VTE developed in a significantly lower proportion of patients treated with enoxaparin (0.3 vs. 1.1%). After three months of follow-up, however, this difference was no longer detectable (3.4 vs. 2.6%). In addition, major bleeding occurred more frequently in the enoxaparin treated group (1.2 vs. 0.6%).

Therefore, present experience consistently supports the view that LMWHs are more effective than UFH for the prevention of proximal DVT, with no additional haemorrhagic risk. They are more effective than oral anti-coagulants for the prevention of in-hospital (mostly distal) DVT, at the price of increased surgical site bleeding and wound haematoma. The choice between LMWH and warfarin should be tailored to the individual patient based on the clinical assessment of postoperative thrombosis and bleeding risk as well as the prophylaxis-specific cost and convenience.

There is still uncertainty about the ideal duration of prophylaxis, despite overwhelming evidence of the efficacy of anti-thrombotics in preventing postoperative VTE after orthopaedic surgery. Concern about the potential risk of pulmonary embolism from symp-tomless DVT, after hospital discharge, has led to the extension of the duration of prophylaxis for up to a month. Whether thrombo-prophylaxis should be extended after hospital discharge, however, is controversial.116--121 Leclerc et al. studied 1984 consecutive patients who underwent hip or knee arthroplasty121 and who received a mean of 9 days enoxaparin prophylaxis (30 mg twice daily). The rates of VTE events during and after prophylaxis at 3 months follow-up were 2.1 and 2.1%, respectively. Following elective hip or knee replacement Heit et al. randomised 1195 patients to LMWH, to stop at the time of hospital discharge or continued for up to 6 weeks after surgery.122 The rate of symptomatic, objectively confirmed VTE after a 3-month follow-up period was similarly low (2 and 1.5%, respectively) in the two groups.

To conclude, the optimal duration of prophylaxis after major orthopaedic surgery remains unclear.

Oncologic surgery

Extensive abdominal or pelvic surgery in cancer patients is associated with a remarkably high risk of developing postoperative VTE. Among pharmacological measures currently utilised for the prevention of postoperative DVT in cancer patients, LMWH have several selective advantage over UFH.123--125

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