Major Orthopedic Surgery

Total Hip Arthroplasty

Studies evaluating the efficacy of pharmacologic versus mechanical (e.g., foot pumps or sequential compression devices) prophylaxis against DVT after elective hip surgery have yielded conflicting findings. Small studies have shown that mechanical devices alone are efficacious in preventing asymptomatic DVT, but compliance with the use of these devices is highly variable. Other studies have shown that pharmacologic prophylaxis is superior to mechanical prophylaxis for the prevention of VTE, but these studies are low quality due to imprecision and high risk for bias. Regarding the different pharmacologic agents, low-molecular-weight heparin (LMWH) has been compared with other anticoagulants. When compared with unfractionated heparin (UFH), patients who received LMWH had fewer incidence of pulmonary embolism, DVT, and major bleeding events. Compared with patients who received a vitamin K antagonist (VKA), those who received LMWH had fewer deep vein thromboses but reported increased bleeding events. The data on factor Xa inhibitors (FXaI) such as fondaparinux, rivaroxaban, and apixaban are mixed, but overall seem to suggest a similar efficacy as LMWH for prevention of VTE and also a similar risk profile for bleeding. Evidence on dabigatran, a direct thrombin inhibitor, is also conflicting. When compared with LMWH, some randomized controlled trials showed inferior efficacy while others revealed comparable efficacy with similar bleeding rates. To date, the data on aspirin for VTE prophylaxis are mixed. Two large nonrandomized control trials compared antiplatelet agents with LMWH, whereas one study found no significant difference in PE and symptomatic DVT between the two treatments, the smaller study found a higher rate of PE in the antiplatelet group. When comparing antiplatelet agents with VKA, one randomized control trial compared the use of intermittent pneumatic compression (IPC) alone, IPC with aspirin, and IPC with VKA, and found no differences in incidence of VTED between the three groups.

Although the rates of asymptomatic DVT are similar for patients with hip fractures and those undergoing elective joint surgery, patients with hip fractures have a significantly higher rate of fatal PE (4%–10%). The reason for this difference is unknown and the exact site of the fracture (subcapital vs intertrochanteric) does not appear to affect the rate of VTED. One small randomized control trial comparing aspirin with IPC alone, found no difference in VTE events. However, pharmacologic intervention has been shown to be far superior to placebo alone. Low-dose unfractionated heparin has been shown to be efficacious in preventing VTED in small uncontrolled studies. Similarly, LMWH and warfarin have also been shown to be effective in larger studies. For hip fracture patients, fondaparinux has been shown to have higher efficacy than enoxaparin for the prevention of VTE, with conflicting results regarding the risk of bleeding complications. The Agency for Health-care Research and Quality (AHRQ) published the largest meta-analysis so far regarding prevention of VTE in major orthopedic surgeries, including hip fracture surgery. They compared different classes of chemotherapy agents.

This review concluded that the data are insufficient to assess the risks and benefits of these different interventions.

Total Knee Arthroplasty

As is the case for total hip arthroplasty, there are conflicting data regarding the various prophylactic regimens for VTED after total knee replacement. It is generally accepted that mechanical devices are less efficacious than pharmacologic agents in preventing asymptomatic DVT after knee arthroplasty. Several randomized controlled trials comparing LMWH with warfarin for the prevention of VTE after total knee replacement have failed to show a difference in PE rate, but LMWH was associated with less DVTs but slightly higher increase in bleeding events. In recent years there has been growing evidence supporting the use of FXaI after total knee arthroplasty. In a meta-analysis, Balk et al. found that FXaI were the most efficacious intervention in preventing DVT following total knee replacement, followed by the combination of LMWH and mechanical prophylaxis. As with previous studies, there were no differences between the rates of symptomatic DVT and fatal PE, most probably a result of inadequate study power to detect such a difference. Aspirin has also been compared with other chemoprophylaxis agents. When compared with FXaI, one randomized control trial showed fewer total DVTs with FXaI and no difference in symptomatic DVT when compared with aspirin. Other studies comparing aspirin with VKA and LMWH found similar results with no significant difference in total or symptomatic DVT with either group.

Recommendations for Prophylaxis Against VTED

Prophylaxis against VTED is currently based more on the danger of PE than on prevention of DVT. Previous studies from the 1970s cited the incidence of fatal PE after joint replacement surgery to be higher than 2% to 3% despite some form of prophylactic anticoagulation. Based on these papers, such operations were considered to be “high risk” for VTED and either mechanical or pharmacologic prophylaxis was encouraged. However, more recent studies have documented an incidence of fatal PE to be only 0.05% to 0.2%, regardless of whether prophylaxis of any modality is used. Possible reasons for the significant decrease in the rate of fatal PE include improved surgical and anesthetic techniques with shorter operative times, faster discharge of patients from the hospital (resulting in earlier mobility), and improved rehabilitation techniques.

Because the incidence of fatal PE is extremely low, some have suggested that pharmacologic prophylaxis is not warranted. They argue that the incidence of fatal PE is nearly equal to the incidence of complications from therapy (e.g., bleeding) and that pharmacologic intervention has not been shown to be more efficacious than mechanical measures alone in preventing symptomatic DVT or PE. Furthermore, the vast majority of deep venous thromboses resolve spontaneously, and thus the risk of bleeding associated with pharmacologic intervention may not be justified. Others, however, note that nonfatal PE and DVT carry substantial morbidity, such as heart strain, respiratory embarrassment, and thrombophlebitis, and thus the risk associated with pharmacologic prophylaxis is justified.

Patients in the intensive care unit (ICU) have limited opportunity for movement because of either the nature of their critical illness or the need for continuous monitoring. Thus it is possible that these patients will have a higher rate of fatal PE and stronger consideration should be given to providing both mechanical and pharmacologic prophylaxis against VTED.

After these guidelines were published, the use of aspirin for VTE prophylaxis in elective knee and hip arthroplasty has been looked at by many studies. One meta-analysis comparing aspirin with other chemoprophylaxis agents, either alone or in combination with mechanical prophylaxis, found a low rate of VTE with a low risk of bleeding. These results were limited by the low quality of the studies, therefore they concluded future randomized controlled trials should investigate the efficacy of aspirin. A more recent meta-analysis by Balk et al. showed that the combination of antiplatelet drug plus mechanical devices had a lower odds of DVT compared with antiplatelet drug alone, UFH heparin, and VKA.

The current guidelines, published in 2012, from the College of Chest Physicians Consensus Conference on Prevention of VTE in orthopedic surgery patients recommend pharmacologic prophylaxis to guard against VTED after total joint replacement surgery. LMWH is the agent of choice for the prophylaxis against VTED and agents such as fondaparinux, apixaban, dabigatran, rivaroxaban, UFH, adjusted-dose warfarin, or aspirin are considered second line agents ( Table 34.1 ). Similarly, The American Academy of Orthopedic Surgeons (AAOS) also recommends pharmacologic prophylaxis against VTE after hip/knee joint arthroplasty. Mechanical and chemical prophylaxis combined is recommended in patients with a past history of VTED.