Intermittent pneumatic compression is virtually free of clinically important side effects and offers a valuable alternative in patients who have a high risk of bleeding. It may produce discomfort in some patients, and should not be used in those with overt evidence leg ischemia caused by peripheral vascular disease. It is also contraindicated if a patient has been at bed rest or immobilized for more than 72 hours without any form of prophylaxis, since it may cause a newly formed clot to disloe.

Intermittent pneumatic leg compression reduces the incidence of venous thrombosis in moderate risk general surgical patients and in patients undergoing neurosurgery or coronary artery bypass grafting [52-54]. It is less effective in patients undergoing hip surgery or knee replacement, preventing calf vein thrombosis but not proximal vein thrombosis [48,55,56]. In a retrospective study of patients recovering from total hip arthroplasty, pneumatic compression reduced the incidence of rehospitalization for symptomatic venous thromboembolism, but only for patients who were not overweight, defined as body mass index less than 25 (show figure 1) [50]. (See "Clinical evaluation of the overweight adult", section on Body mass index).

A variety of well accepted, comfortable, and effective intermittent pneumatic devices are currently available which may be applied preoperatively, at the time of surgery, or in the early postoperative period. These devices should be used continuously until the patient is fully ambulatory, with only temporary removal for nursing care or physiotherapy. With the rapidly decreasing length of stay in patients undergoing orthopedic surgery, the use of IPC devices has decreased. Furthermore, compliance with these devices has been problematic. In a prospective review it was shown that the duration and degree of compression was suboptimal in patients undergoing total hip replacement when intermittent compression was the sole form of prophylaxis [57].

Intermittent compression devices are useful in the early postoperative period in patients who are at high risk for bleeding, such as following intracranial surgery or for patients who have epidural catheters for extended analgesia. Pharmacologic agents can be commenced when the risk of bleeding has decreased. Pneumatic compression may be used in conjunction with LMWH in patients considered at very high risk of post-operative venous thromboembolism [15].

Graduated compression stockings — Graduated compression stockings reduce venous stasis in the limb by applying a graded degree of compression to the ankle and calf, with greater pressure b**** applied distally. They reduce the incidence of postoperative venous thrombosis only in low risk general surgical patients [58] and in selected moderate risk patients (eg, neurosurgical) [40,41,53,59]. It is unclear whether the use of graduated compression stockings in combination with other forms of prophylaxis results in any further risk reduction [60].

Aspirin — Although meta-analyses indicate that aspirin decreases the frequency of venous thrombosis following general or orthopedic surgery, this reduction is significantly less than that obtained using other agents [61]. Based upon these findings, a multinational trial randomly assigned 13,356 patients undergoing surgery for hip fracture and 4088 patients undergoing elective hip or knee arthroplasty to receive placebo or 160 mg/day of aspirin for 35 days, in addition to other thromboprophylactic measures (eg, subcutaneous heparin) prescribed at the discretion of the treating physician [62]. Fatal pulmonary embolism and deep venous thrombosis were both significantly reduced by the addition of aspirin (each with an absolute risk reduction of 0.4 percent), while fatal and non-fatal arterial events (myocardial infarction or stroke) and all cause mortality which were the primary end points for the study were not decreased. Wound related and gastrointestinal bleeding and the need for transfusion were significantly more common in the aspirin treated group.

Thus, aspirin may have some activity in preventing venous thromboembolism, but its lower efficacy than other measures precludes its use as monotherapy in most cases, and its therapeutic index when used alone or in conjunction with other anticoagulants has not been well defined. Therefore, aspirin cannot be recommended at present for the prophylaxis of venous thrombosis [63].

Fondaparinux — The synthetic heparin pentasaccharide fondaparinux (Arixtra, Org31540/SR90107A) catalyzes factor Xa inactivation by AT III without inhibiting thrombin [64,65]. The efficacy of fondaparinux has been demonstrated in patients undergoing major orthopedic surgery in whom there was an overall 50 to 60 percent reduction in risk of venous thromboembolic disease, primarily distal DVT, when compared to low molecular weight heparin [39,66,67]. In a separate study, use of fondaparinux for one month, rather than one week, reduced the incidence of documented VTE from 35 to 1.4 percent [68]. (See "Clinical use of fondaparinux", section on Hip fracture surgery).

Fondaparinux was approved by the FDA for the prophylaxis of deep vein thrombosis in patients undergoing surgery for hip fracture, hip replacement, or knee replacement in December, 2001. The cost of treatment with fondaparinux has been estimated at approximately $44 per day; in comparison, the costs of unfractionated heparin and low molecular weight heparin are $2 to $3 and $24 to $35 dollars per day, respectively [69].

Investigational agents — Initial studies with the orally active synthetic antithrombin agent ximelagatran (Exanta) have shown promising results in preventing VTE in patients undergoing hip or knee replacement surgery when compared with LMWH [70-72] or warfarin [73,74]. (See "New anticoagulants", section on Ximelagatran).

A dose finding study has also been reported with the use of the nematode anticoagulant protein (rNAPc2, which inhibits the tissue factor-activated factor VII complex) in patients undergoing total knee replacement [75]. This agent also shows promise with respect to both efficacy and safety in this setting. Further published reports with these agents are awaited with interest to determine their future role in prophylaxis of venous thromboembolism in high-risk patients.

Low molecular weight heparin can be made absorbable through the gastrointestinal tract [5,76]. An international multicenter study is underway comparing the efficacy and safety of oral heparin in two dose regimens with LMWH for the prevention of venous thromboembolism following total hip replacement surgery.

A number of other investigations are underway with new antithrombotic agents. Most of the current interest is in the development of oral factor Xa inhibitors.

RECOMMENDATIONS — The primary prophylactic approach depends upon the patient's risk category and the type of surgery (show table 1). The recommendations that follow are derived from randomized trials with low false positive and false negative errors unless otherwise stated. Readers are referred to the report on the "Prevention of venous thromboembolism" for the Seventh American College of Chest Physicians Consensus Conference on Antithrombotic Therapy for complete details [63]. The following are general recommendations:

Each hospital should develop a formal strategy for the prevention of venous thromboembolism all risk categories for surgical and medical patients [6].
The use of aspirin for prophylaxis in all patients groups is not recommended, as other measures are more efficacious.
The use of routine ultrasonography screening at discharge or during outpatient follow-up is not recommended in asymptomatic patients.
Antithrombotic prophylaxis should be used with caution in patients having spinal puncture or epidural catheter placement for regional anesthesia or continued analgesia. The recommendations of the American Association for Regional Anaesthesia should be consulted [75,76].
Low risk surgical patients — Prophylaxis other than early ambulation usually is not recommended in low risk patients [63]. However, prophylaxis may be used in certain circumstances. It is the custom in some countries to use graduated compression stockings, but this practice is not based upon evidence from clinical trials.

Moderate risk surgical patients — The following are recommendations for prophylaxis in moderate risk patients: