Risk Factors

In patients undergoing total hip arthroplasty (THA), total knee arthroplasty, or hip fracture surgery, 1% to 3% will go on to have a symptomatic DVT, whereas 0.2% to 1.1% will go on to have a PE within 35 days of surgery. The first postoperative week is the period of highest risk for symptomatic PE development. In addition to identifying the period in which patients are at risk for VTE, identifying which patients’ characteristics are associated with a higher risk is essential in guiding diagnostic and management efforts.

Certain patient characteristics, such as age and a history of a previous VTE, may pose primary risk factors for unprovoked VTE in the emergent setting. In the ninth decade of life, the incidence of emergent PE is 1 in 200 patients, whereas in the third decade of life the incidence is only 1 in 10,000 patients. Risk associated with age for emergent PE development is most significant after the age of 50 and increases until the age of 80 years. A history of prior VTE is also a risk factor for emergent PE, causing a 2- to 3-fold increase in risk of future unprovoked VTE in men. Surgery requiring intubation, immobility, and estrogen also transiently increase the risk of provoked PE. In surgical patients, the risk of VTE extends for months and even potentially for a year. Although sex, smoking, congestive heart failure, cancer, and obesity are commonly thought to be risk factors for DVT and PE, there is not enough evidence to consider these as primary risk factors. With specific regard to risk factors for VTE in orthopedic patients, the American Academy of Orthopedic Surgeons (AAOS) guidelines report that, with the exception of a history of VTE, the current evidence is inconclusive as to whether other factors increase the risk of VTE in patients undergoing elective arthroplasty and, therefore, does not recommend routinely assessing patients for these factors.

Diagnosis

When suspecting DVT and PE, and before conducting any further testing, it is important to initially establish a level of pretest probability. The Wells clinical prediction criteria is used to establish whether a patient has a low, intermediate, or high pretest risk for PE development. It considers the presence of certain risk factors, signs of DVT, and the likelihood of an alternative diagnosis. A meta-analysis of 15 studies reported that patients with the highest pretest probability had a prevalence of DVT ranging from 17% to 85%, whereas those with a moderate pretest probability had a prevalence of 0% to 38%, and patients with the lowest pretest probability had a prevalence of 0% to 13%. These results suggest that Wells clinical prediction rule is not definitive and should be only used to establish probability assessment and to guide further diagnostic and screening tests.

There are several imaging modalities currently used to confirm or rule out the diagnosis of DVT and PE. The current gold standard diagnostic techniques are venography and pulmonary angiography, respectively; however, because of exorbitant cost and the invasive nature of these tests, their role in diagnosis has become limited. Therefore, less-invasive tests are sought after to play a more significant role in ruling in or out DVT and PE diagnoses.

Currently, one of the most common noninvasive diagnostic tests for DVT is venous compression ultrasonography (CUS). When attempting to diagnose proximal DVT, CUS has been reported to have a sensitivity and specificity of 97% and 98%, respectively. Patients with low pretest probability combined with a negative CUS can be safely withheld from anticoagulant therapy. CUS is not frequently used to detect distal DVT, as the sensitivity and specificity are much lower, and controversy exists as to whether to treat isolated distal DVT.

Another safe and cost-effective way of evaluation is a D-dimer assay. D-dimers are products of cross-linked fibrin breakdown by plasmin produced at the site of thrombosis. Although no biomarker exists that is both 100% sensitive and specific for VTE, D-dimer is a very sensitive laboratory test, and a negative assay in combination with a low pretest probability of VTE is useful in ruling out the presence of DVT and PE. However, studies have found that an elevated D-dimer is also seen in various clinical scenarios, including sepsis, pregnancy, malignancy, and after surgery, making the test nonspecific with limited use in ruling in DVT or PE in these settings. The current AAOS guidelines therefore conclude that D-dimer is not a reliable marker to screen for DVT after arthroplasty. In the event of an elevated D-dimer assay in which PE may not be ruled out, imaging must be ordered. In patients with impaired renal function (glomerular filtration rate <60 mL/min), a ventilation-perfusion scan may be used. In patients with a nondiagnostic ventilation-perfusion scan or adequate renal function, a computed tomographic pulmonary angiogram may be used to confirm or exclude the diagnosis of PE and to guide prospective management.

Prophylaxis

Given the substantial morbidity and mortality and increased health care burden associated with the incidence of VTE, the most effective way to begin management is through primary prevention ( Table 1 ). Because VTE is difficult to diagnose with absolute certainty, it is often misdiagnosed; therefore, treatment is not possible in every case.

Pharmacologic thromboprophylaxis is commonly used in postoperative orthopedic patients to prevent VTE. One of the challenges in using pharmacologic agents is balancing benefits of anticoagulation and the risk of bleeding complications. To help achieve this balance, current AAOS treatment guidelines moderately recommend discontinuing antiplatelet agents before undergoing elective hip or knee arthroplasty to reduce the bleeding risk during surgery and using anticoagulation postoperatively to prevent VTE.

Low-molecular-weight heparin (LMWH), fondaparinux, dabigatran, apixaban, and rivaroxaban may be used after THA or total knee arthroplasty. Apixaban showed greater safety and similar efficacy when compared with LMWH, whereas rivaroxaban showed greater efficacy and similar safety when compared with LMWH in hip and knee arthroplasties. LMWH and fondaparinux are preferentially used specifically in patients undergoing surgical treatment for femoral neck fracture. In orthopedic patients with nonhip fractures and soft tissue injuries such as cartilage or tendon injuries or patients undergoing arthroscopy, pharmacologic thromboprophylaxis is not routinely recommended according to current guidelines.

For those patients in whom warfarin is used as prophylaxis, it is recommended that it is begun the night before surgery. The dose should then be adjusted postoperatively to a target international normalized ratio (INR) of 2.2. When compared with a 2-step regimen in which warfarin is started 10 to 14 days preoperatively and titrated to an INR of 2.2 to 3, this regimen has an equal benefit regarding VTE prevention and may cause less perioperative bleeding. Prophylaxis with warfarin has been found to decrease asymptomatic DVT by 55% and PE by 80%.

When LMWH is used for prophylaxis, there are questions regarding whether it should be started preoperatively or held until the postoperative period. Enoxaparin, 30 to 40 mg twice daily, is the prophylactic dose most commonly used. LMWH decreases the risk of DVT by 50% to 60% and the risk of PE by approximately two-thirds. Some guidelines recommend starting LMWH either 12 hours or more preoperatively or 12 hours or more postoperatively in arthroplasty and hip fracture patients. If LMWH is administered between 2 hours preoperatively and 4 hours postoperatively, the rate of major bleeding is 5% to 7%. In comparison, starting LMWH 12 hours preoperatively or waiting until 12 to 24 hours postoperatively has a risk of major bleeding of only 1% to 3%. Although LMWH has typically been given, no difference was found in the rate of PE between patients using LMWH and those using warfarin. However, studies indicated that LMWH is associated with significantly less asymptomatic DVT and more major bleeding. Fitzgerald and colleagues reported the odds ratio in patients taking warfarin for development of DVT to be 2.52 when compared with those taking enoxaparin. However, the rate of hemorrhage complications was higher in patients taking enoxaparin (7% vs 3%).

Although several pharmacologic prophylactic strategies are effective, safe, and readily available, these drugs are not without risk or drawbacks for certain patients. Some of the drawbacks to using anticoagulants for thromboprophylaxis in orthopedic patients include the need for repetitive laboratory testing, monitoring, anxiety and pain with self-injection, and the risk of postoperative bleeding complications. Therefore, other nonpharmacologic thromboprophylactic strategies are available as alternative options. One noninvasive, nonpharmaceutical, and inexpensive option is the use of lower extremity pneumatic compression devices (PCD). Evidence suggests that PCDs with intermittent compression are effective in preventing DVT; however, their use has been limited in the inpatient setting because of concerns with comfort and compliance. Interestingly, one study reported that postoperative THA patients who used a mobile compression device reported an overall positive response and would choose to use this method again in the future rather than using pharmacologic thromboprophylaxis. Unfortunately, there is little evidence to suggest how long patients should use PCDs postoperatively to most effectively prevent DVT occurrence. Although current AAOS guidelines moderately recommend the use of either pharmacologic or mechanical compression devices for VTE prophylaxis, they mention that current evidence is inconclusive as to which prophylactic strategy is superior. Further studies comparing the relative effectiveness of different VTE prophylaxis strategies would be useful in making decisions about which methods should be used over others in various patient types.

Another method of thromboprophylaxis that may be used as a PE prevention strategy is the placement of an inferior vena cava (IVC) filter. IVC filters may be used in combination with anticoagulants for patients who are at high risk of suffering a PE. When used in combination with anticoagulants or mechanical compression therapy in high-risk orthopedic patients, IVC filters are found to effectively prevent PE. Additionally, IVC filters may be useful in patients who cannot tolerate anticoagulants or have a high risk of bleeding with anticoagulant use. Some other indications of IVC filters include use in high-risk burn or trauma patients, patients with a free-floating iliofemoral thrombus, or in patients undergoing iliocaval thrombolysis or pulmonary thrombectomy. Although there may be some benefits of using IVC filters, serious potential adverse effects include risk of recurrent DVT, IVC thrombosis, migration of the device, infection, and inability to retrieve the device. The risk of adverse events increases with the duration of filter placement; therefore, the benefits of IVC filters are best achieved with short-term placement.

Intervention

In cases of prophylaxis failure, symptomatic and potentially devastating PE may develop and must be treated aggressively. Within 1 hour of PE presentation, complications such as right ventricular (RV) strain, cardiac arrest, and heart failure may occur, resulting in mortality rates as high as 70%. In the event of acute or submassive PE diagnosed by computed tomography imaging, anticoagulation with intravenous heparin and supplemental oxygen therapy is initiated. The next step in treatment is determined by whether the patient is hemodynamically stable or unstable. In case of hemodynamic stability, echocardiography should be used to investigate the presence of RV dysfunction. If RV dysfunction is not present, then conservative management with anticoagulation is indicated. However, in the setting of a hemodynamically unstable patient or RV dysfunction, a surgical embolectomy is indicated. If in a given setting in which a facility does not have cardiac surgical capabilities, then thrombolysis or catheter embolectomy may be indicated. Evidence suggests that surgical embolectomy is a more successful treatment strategy with relatively low morbidity, mortality, and recurrence rates compared with thrombolysis.