Which assessment would support that the client has experienced a pulmonary embolism?

Symptoms and Signs of Pulmonary Embolism

Many pulmonary emboli are small, physiologically insignificant, and asymptomatic. Even when present, symptoms are nonspecific and vary in frequency and intensity, depending on the extent of pulmonary vascular occlusion and preexisting cardiopulmonary function.

Emboli often cause

• Acute dyspnea

• Pleuritic chest pain (when there is pulmonary infarction)

Dyspnea may be minimal at rest and can worsen during activity.

Less common symptoms include

• Cough (usually caused by comorbid disorders)

• Hemoptysis (occasionally occurs when there is pulmonary infarction)

In elderly patients, the first symptom may be altered mental status.

Massive pulmonary emboli may manifest with hypotension, tachycardia, light-headedness/presyncope, syncope, or cardiac arrest.

The most common signs of pulmonary embolism are

• Tachycardia

• Tachypnea

Less commonly, patients have hypotension. A loud 2nd heart sound (S2) due to a loud pulmonic component (P2) is possible but uncommon in acute PE because increases in pulmonary artery pressures are only modest. Crackles or wheezing may occur but is usually due to comorbid disease. In the presence of right ventricular failure, distended internal jugular veins and a RV heave may be evident, and a RV gallop (3rd heart sound [S3]), with or without tricuspid regurgitation, may be audible.

Fever, when present, is usually low-grade unless caused by an underlying condition.

Pulmonary infarction is typically characterized by chest pain (mainly pleuritic) and, occasionally, hemoptysis. The chest wall may be tender.

Chronic thromboembolic pulmonary hypertension causes symptoms and signs of right heart failure, including exertional dyspnea, easy fatigue, and peripheral edema that develops over months to years.

Clinical probability of pulmonary embolism can be assessed by combining ECG and chest x-ray findings with findings from the history and physical examination. Clinical prediction scores, such as the Wells score or the revised Geneva score (1 Diagnosis reference Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more

One of the important clinical criteria is a judgment of whether PE is more likely than an alternate diagnosis, and this determination is somewhat subjective. However, the clinical judgment of experienced clinicians is as sensitive as, or even more sensitive, than results from formal prediction scores. PE should probably be considered more likely if one or more of the symptoms and signs, particularly dyspnea, hemoptysis, tachycardia, or hypoxemia, cannot be explained clinically or by chest x-ray results.

Pretest probability guides testing strategy and the interpretation of test results. In patients in whom the probability of PE is unlikely, only minimal additional testing (ie, D-dimer testing in outpatients) may be needed. In such cases, a negative D-dimer test (< 0.4 mcg/mL [< 2.2 nmol/L]) is highly indicative of the absence of pulmonary embolism. Conversely, if there is a high clinical suspicion of PE and the risk of bleeding is low, immediate anticoagulation should be considered while the diagnosis is confirmed with additional tests.

The PERC rule specifies 8 criteria. Presence of these criteria in a clinically low-risk patient specifies that testing for PE is not indicated. The criteria are:

• Age < 50 years

• HR < 100

• Oxygen saturation ≥ 95%

• No prior deep venous thrombosis or pulmonary embolism

• No unilateral leg swelling

• No estrogen use

• No hemoptysis

• No surgery or trauma requiring hospitalization within the past 4 weeks

Use of the PERC rule has been recommended as a way to decrease rates of testing for PE with conventional testing using D-dimer, but with similar rates of sensitivity and negative predictive values.

• Screening of outpatients with D-dimer testing if pre-test probability is low or of intermediate probability

• If pretest probability is likely or if D-dimer result is elevated, CT angiography, or if renal insufficiency is present or when CT contrast is contraindicated, with ventilation/perfusion (V/Q) scanning

• Sometimes ultrasonography of the legs or arms (to confirm DVT when lung imaging is delayed or prohibitive)

There is no universally accepted algorithm for the approach to suspected acute pulmonary embolism. Tests most useful for diagnosing or excluding PE are

• D-dimer testing

• CT angiography

• Ventilation/perfusion scanning

• Duplex ultrasonography

Echocardiography may be useful to identify pulmonary embolism on the way to the lung (clot-in-transit).

D-Dimer is a by-product of intrinsic fibrinolysis; thus, elevated levels occur in the presence of a recent thrombus. When pretest probability is considered low or intermediate, a negative D-dimer level (< 0.4 mcg/mL [< 2.2 nmol/L]) is highly sensitive for the absence of PE with a negative predictive value of > 95%; in most cases, this result is sufficiently reliable for excluding the diagnosis of PE in the outpatient setting such as the emergency department or clinic. However, elevated D-dimer levels are not specific for venous thrombus because many patients without deep venous thrombosis (DVT) or PE also have elevated levels (particularly in the inpatient setting), and therefore, further testing is required when the D-dimer level is elevated or when the pretest probability for PE is high.

CT angiography is the preferred imaging technique for diagnosing acute pulmonary embolism. It is rapid, accurate, and highly sensitive and specific. It can also give more information about other lung pathology (eg, demonstration of pneumonia rather than PE as a cause of hypoxia or pleuritic chest pain) as well as severity of PE (for example by the size of the right ventricle or the reflux into the hepatic veins). Although poor quality scans due to motion artifact or poor contrast boluses can limit the sensitivity of the examination, improvements in CT technology have shortened acquisition times to less than 2 seconds, providing relatively motion-free images in patients who are dyspneic. Fast scanning times allow the use of smaller volumes of iodinated contrast, which reduces the risk of acute kidney injury.

The sensitivity of CT angiography is highest for pulmonary embolism in the main pulmonary artery and lobar and segmental vessels. Sensitivity of CT angiography is lowest for emboli in subsegmental vessels (about 30% of all pulmonary emboli). However, the sensitivity and specificity of CT angiography have improved as technology has evolved.

Ventilation/perfusion (V/Q) scans in pulmonary embolism detect areas of lung that are ventilated but not perfused. V/Q scanning takes longer than CT angiography and is less specific. However, when chest x-ray findings are normal or near normal and no significant underlying lung disease exists, it is a highly sensitive test. V/Q scanning is particularly useful when renal insufficiency precludes the use of contrast that is otherwise required for CT angiography. In some hospitals, V/Q scanning can be done with a portable machine that provides 3 views of ventilation and perfusion, which is useful when a patient is too ill to move. Perfusion defects may occur in many other lung conditions (eg, COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more

Results are based on patterns of V/Q mismatch and typically are reported as

• Normal: Excludes PE with nearly 100% accuracy

• Very low probability: < 5%

• Low probability: 15% likelihood of PE

• Intermediate probability: 30 to 40% probability of PE

• High probability: 80 to 90% probability of PE

The results of clinical probability testing must be used together with the scan result to determine the need for treatment or further testing.

Duplex ultrasonography is a safe, noninvasive, portable technique for detecting leg or arm thrombi. A clot can be detected by showing poor compressibility of the vein or by showing reduced flow by Doppler ultrasonography. The test has a sensitivity of > 95% and a specificity of > 95% for thrombus. Confirming DVT in the calf or iliac veins can be more difficult but can generally be accomplished. The ultrasound technician should always attempt to image below the popliteal vein into its trifurcation.

Absence of thrombi in the leg veins does not exclude the possibility of thrombus from other sources, such as the upper extremities, but patients with suspected DVT and negative results on Doppler duplex ultrasonography have > 95% event-free survival, because thrombi from other sources are so much less common.

Although ultrasonography of the legs or arms is not diagnostic for PE, a study that reveals leg or axillary-subclavian thrombus establishes the need for anticoagulation and may obviate the need for further diagnostic testing unless more aggressive therapy (eg, thrombolytic therapy) is being considered. Therefore, stopping the diagnostic evaluation after detection of DVT on ultrasonography of the legs or arms is most appropriate for stable patients with contraindications to CT contrast and in whom V/Q scanning is expected to have low specificity (eg, in patients with an abnormal chest x-ray). In suspected acute PE, a negative ultrasound does not negate the need for additional studies.

Echocardiography may show a clot in the right atrium or ventricle, but echocardiography is most commonly used for risk stratification in acute PE. The presence of right ventricular dilation and hypokinesis may suggest the need for more aggressive therapy.

Cardiac marker testing is evolving as a useful means of stratifying mortality risk in patients with acute pulmonary embolism. Cardiac marker testing can be used as an adjunct to other testing if PE is suspected or proven. Elevated troponin levels signify right ventricular (or sometimes left ventricular) ischemia. Elevated brain natriuretic peptide (BNP) and pro-BNP levels may signify RV dysfunction; however, these tests are not specific for RV dysfunction or for PE.

Pulmonary arteriography is now rarely needed to diagnose acute PE because noninvasive CT angiography has similar sensitivity and specificity. However, in patients in whom catheter-based thrombolytic therapy is being used, pulmonary angiography is useful for assessment of catheter placement and may be used as a rapid means of determining success of the procedure when the catheter is removed. Pulmonary arteriography is also still used together with right-heart catheterization in assessing whether patients with chronic thromboembolic pulmonary hypertension are candidates for pulmonary endarterectomy.

• 1. Le Gal G, Righini M, Roy PM, et al: Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 144:165–171, 2006.

• 1. Kabrhel C, Jaff MR, Channick RN, et al: A multidisciplinary pulmonary embolism response team. Chest 144(5):1738–1739, 2013. doi: 10.1378/chest.13-1562

Initial anticoagulation choices for acute PE include

• Intravenous unfractionated heparin

• Subcutaneous low molecular weight heparin

• Subcutaneous fondaparinux

• Factor Xa inhibitors (apixaban and rivaroxaban)

• Intravenous argatroban for patients with heparin-induced thrombocytopenia

Intravenous unfractionated heparin has a short half-life (useful when the potential for bleeding is deemed higher than usual) and is reversible with protamine. An initial bolus of unfractionated heparin is given, followed by an infusion of heparin dosed by protocol to achieve an activated PTT 1.5 to 2.5 times that of normal control (see figure Weight-based heparin dosing Weight-based dosing

Weight-based dosing

Subcutaneous low molecular weight heparin has several advantages over unfractionated heparin including

• Superior bioavailability

• Weight-based dosing results in a more predictable anticoagulation effect than does weight-based dosing of unfractionated heparin

• Ease of administration (can be given subcutaneously once or twice a day)

• Decreased incidence of bleeding

• Potentially better outcomes

• The potential for patients to self-inject (thereby allowing earlier discharge from the hospital)

• Lower risk of heparin-induced thrombocytopenia compared with standard, unfractionated heparin

In patients with renal insufficiency, dose reductions are needed (see table Some Low Molecular Weight Heparin Options in Thromboembolic Disease Some Low Molecular Weight * Options in Thromboembolic Disease

Adverse effects of all heparins include

• Bleeding

• Urticaria

• Anaphylaxis (rare)

Bleeding caused by over-heparinization with unfractionated heparin can be treated with a maximum of 50 mg of protamine per 5000 units unfractionated heparin infused over 15 to 30 minutes. Over-heparinization with a low molecular weight heparin can be treated with protamine 1 mg in 20 mL normal saline infused over 10 to 20 minutes, although the precise dose is undefined because protamine only partially neutralizes low molecular weight heparin inactivation of factor Xa.

Fondaparinux is a factor Xa antagonist given subcutaneously. It can be used in acute DVT and acute PE instead of heparin or low molecular weight heparin. It has also been shown to prevent recurrences in patients with superficial venous thrombosis. Outcomes appear to be similar to those of unfractionated heparin. Advantages include once or twice a day fixed-dose administration, no need for monitoring of the degree of anticoagulation, and lower risk of thrombocytopenia. The dose (in mg/kg once a day) is 5 mg for patients < 50 kg, 7.5 mg for patients 50 to 100 kg, and 10 mg for patients > 100 kg. Fondaparinux dose is decreased by 50% if creatinine clearance is 30 to 50 mL/minute (0.5 to 0.83 mL/second). The drug is contraindicated if creatinine clearance is < 30 mL/minute.

Dose reductions are indicated for patients with renal insufficiency. Apixaban can be used in patients with renal insufficiency and data suggest use is safe in patients undergoing hemodialysis.

Anticoagulation reversal of the oral Xa inhibitors (rivaroxaban, apixaban, edoxaban) is possible with andexanet, although this drug is not widely used at this time. Also, the half-lives of the newer factor Xa inhibitors are much shorter than the half-life for warfarin. If bleeding develops that requires reversal, use of 4-factor prothrombin complex concentrate can be considered, and hematology consultation is recommended.

The safety and efficacy of these drugs in patients with pulmonary embolism complicated by severe cardiopulmonary decompensation have not yet been studied, and parenteral drugs should be used for anticoagulation in these patients until there is significant improvement in cardiopulmonary function.

The direct thrombin inhibitor dabigatran has also proven effective for treatment of acute DVT and PE. Idarucizumab has proven effective at reversing dabigatran.

Maintenance anticoagulation is indicated to reduce the risk of clot extension or embolization and to reduce the risk of new clot formation. Drug choices for maintenance anticoagulation include

• Oral vitamin K antagonist (warfarin in the US)

• Oral factor Xa inhibitors (apixaban, rivaroxaban, edoxaban)

• Oral direct thrombin inhibitor (dabigatran)

• Rarely subcutaneous low molecular weight heparin

Warfarin is an effective long-term oral anticoagulant option that has been used for decades, but it is very inconvenient for a number of reasons. In most patients, warfarin is started on the same day as heparin (or fondaparinux) therapy used for initial anticoagulation. Heparin (or fondaparinux) therapy should be overlapped with warfarin therapy for a minimum of 5 days and until the INR has been within the therapeutic range (2.0 to 3.0) for at least 24 hours.

The major disadvantages of warfarin are the need for periodic INR monitoring, with frequent dose adjustments, and drug interactions. Physicians prescribing warfarin should be wary of drug interactions; in a patient taking warfarin, virtually any new drug should be checked.

Bleeding is the most common complication of warfarin treatment; patients > 65 years and those with comorbidities (especially diabetes, recent myocardial infarction, hematocrit < 30%, or creatinine > 1.5 mg/dL [>133 micromol/L]) and a history of stroke or gastrointestinal bleeding seem to be at greatest risk. Bleeding can be reversed with vitamin K 2.5 to 10 mg IV or orally and, in an emergency, with fresh frozen plasma or a new concentrate formulation (prothrombin complex concentrates) containing factor II (prothrombin), factor VII, factor IX, factor X, protein C, and protein S. Vitamin K may cause flushing, local pain, and, rarely, anaphylaxis.

The oral factor Xa inhibitor anticoagulants apixaban and rivaroxaban can be used for both initial and maintenance anticoagulation therapy (see table Oral Anticoagulants Oral Anticoagulants

Edoxaban requires that a preceding 5 to 10 days of initial heparin or low molecular weight heparin be given.

The direct thrombin inhibitor dabigatran can also be used for maintenance anticoagulation therapy. As with edoxaban, 5 to 10 days of treatment with unfractionated heparin or low molecular weight heparin is needed before dabigatran can be initiated. Clinically relevant bleeding is lower with dabigatran than with warfarin. The use of dabigatran as maintenance therapy has the same advantages and disadvantages as the use of the factor Xa inhibitors.

The need for initial heparin treatment before edoxaban or dabigatran is given is a reflection of the way the clinical trials were conducted.

Duration of maintenance anticoagulation for PE is dependent on a variety of factors (eg, risk factors for PE, bleeding risk) and can range from 3 months to lifelong therapy. Clearly transient risk factors (eg, immobilization, recent surgery, trauma) require only 3 months of treatment. Patients with unprovoked PE, those with more durable risk factors for PE (eg, cancer, thrombophilic disorder), and those with recurrent PE might benefit from lifelong anticoagulation provided the bleeding risk is low or moderate. In many patients, degree of risk is less clear (eg, with a minor precipitating factor such as a 4 hour flight); for them, rather than stopping rivaroxaban or apixaban at 6 months, dosage can be decreased.

Risk factors for bleeding include

• Age > 65 years

• Previous bleeding

• Thrombocytopenia

• Antiplatelet therapy

• Poor anticoagulant control

• Frequent falls

• Liver failure

• Alcohol abuse

• Recent surgery

• Reduced functional capacity

• Previous stroke

• Diabetes

• Anemia

• Cancer

• Renal failure

Low risk for bleeding is defined as no bleeding risk factors, moderate risk for bleeding is defined as one risk factor, and high risk for bleeding is defined as two or more risk factors.

As described above, after 6 months of treatment with rivaroxaban or apixaban, dosage decreases can be considered.

• 5. van Es N, Coppens M, Schulman S, et al: Direct oral anticoagulants compared with vitamin K antagonists for acute symptomatic venous thromboembolism: evidence from phase 3trials. Blood124 (12): 1968–1975, 2014.

• 6. Young AM, Marshall A, Thirlwall J, et al: Comparison of an oral factor Xa inhibitor with LMWH in patients with cancer with VTE Results of a randomized trial (SELECT-D). J Clin Oncol 36 (20):2017–2029, 2018.

• 7. Weitz JI, Lensing AWA, Prins MH, et al: Rivaroxaban or aspirin for extended treatment of venous thromboembolism. N Engl J Med 376:1211–1222, 2017. doi: 10.1056/NEJMoa1700518. Epub 2017 Mar 18.

Systemic thrombolytic therapy with alteplase (tissue plasminogen activator [tPA]) offers a noninvasive way to rapidly restore pulmonary blood flow, but use is controversial because long-term benefits do not clearly outweigh the risk of hemorrhage. Regardless, most experts agree that systemic thrombolytic therapy should be given to patients with hemodynamic compromise, particularly when it is severe. Although no single prospective randomized trial of systemic thrombolytic therapy has shown improved survival in patients with submassive PE, some experts recommend thrombolytics, particularly when patients also have numerous or large clots, very severe RV dysfunction, marked tachycardia, significant hypoxemia, and other concomitant findings such as residual clot in the leg, positive troponin values, and/or elevated BNP values. Others reserve thrombolytic therapy only for patients with massive (high-risk) PE. Streptokinase and urokinase generally are no longer used.

Absolute contraindications to thrombolytics include

• Prior hemorrhagic stroke

• Ischemic stroke within 1 year

• Active external or internal bleeding from any source

• Intracranial injury or surgery within 2 months

• Intracranial tumor

• Certain surgeries within the previous few days

Relative contraindications include

• Recent surgery (≤ 10 days)

• Hemorrhagic diathesis (as in hepatic insufficiency)

• Pregnancy

• Recent punctures of large noncompressible veins (eg, subclavian or internal jugular veins)

• Recent femoral artery catheterization (eg, ≤ 10 days)

• Peptic ulcer disease or other conditions that increase the risk of bleeding

• Severe hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg)

• Head trauma from PE-induced syncope, even if brain CT is normal

Except for concurrent intracerebral hemorrhage, thrombolytic therapy is sometimes given to patients with massive PE who have "absolute contraindications" to such therapy if death is otherwise expected. In patients with relative contraindications, the decision to give systemic thrombolytics depends on individual patient factors.

In the US, when systemic thrombolytics are given, heparin is usually stopped after the initial loading dose. However, in Europe, heparin is often continued, and there is no clear determination as to which method is preferred. The bleeding risk should be considered.

Bleeding, if it occurs, can be reversed with cryoprecipitate or fresh frozen plasma. Accessible vascular access sites that are bleeding can be compressed. The potential for bleeding after systemic thrombolysis has led to increased implementation of catheter-based thrombolysis, because much lower doses of thrombolytic agents are used.

Catheter-directed PE therapy (thrombolytics, embolectomy) uses catheter placement in the pulmonary arteries for disruption and/or lysis of clot. It is used to treat massive PE. Indications for the treatment of submassive PE are evolving. Studies to date, including prospective randomized clinical trials, have demonstrated that this approach leads to an improved RV/LV ratio at 24 hours compared with anticoagulation alone. Other outcomes and safety of catheter-based therapy compared to systemic thrombolysis are under investigation.

In catheter-based PE thrombolytic therapy, the pulmonary arteries are accessed via a typical right-heart catheterization/pulmonary arteriography procedure, and thrombolytics are delivered directly to large proximal emboli via the catheter. The most widely studied technique uses high-frequency, low-power ultrasonography to facilitate delivery of the thrombolytics. Ultrasonography accelerates the thrombolytic process by disaggregating fibrin strands and increasing permeability of lytic drug into the clot. Standard dosing has been 20 to 24 mg of tPA over 15 or more hours, but lower doses and shorter durations have been shown to be effective with this technique.

Other clot extraction techniques involve catheter-directed vortex suction embolectomy, sometimes in combination with extracorporeal bypass. Catheter-directed vortex suction embolectomy differs from systemic thrombolysis and catheter-based PE thrombolytic therapy in that a larger bore catheter is required and blood that is suctioned out must be redirected out back into a vein (usually femoral). Patients with venal caval, right atrial, or right ventricular thrombi-in-transit are the best candidates. The pulmonary arteries are difficult to access with the current devices. Veno-arterial extracorporeal membrane oxygenation (ECMO) may be used as a rescue procedure in severely ill patients with acute PE, regardless of what other therapies are used. Other smaller suctioning devices are now available.

Surgical embolectomy is reserved for patients with PE who are hypotensive despite supportive measures (persistent systolic blood pressure ≤ 90 mm Hg after fluid therapy and oxygen or if vasopressor therapy is required) or on the verge of cardiac or respiratory arrest. Surgical embolectomy should be considered if use of thrombolysis is contraindicated; in such cases, catheter-directed vortex embolectomy may also be considered and, depending on local resources and expertise, tried before surgical embolectomy. Surgical embolectomy appears to increase survival in patients with massive PE but is not widely available. As with catheter-based thrombosis/clot extraction, the decision to proceed with embolectomy and the choice of technique depend on local resources and expertise.

Extracorporeal membrane oxygenation (ECMO) has been used increasingly in catastrophic acute pulmonary embolism when thrombolysis is contraindicated or failed. ECMO may serve as a bridge to surgical embolectomy or catheter-directed therapy, or it may buy time for improvement with anticoagulation alone.

Prevention of pulmonary embolism means prevention of deep venous thrombosis (DVT); the need depends on the patient’s risks, including

• Type and duration of any surgery

• Comorbid conditions, including cancer and hypercoagulable disorders

• Presence of a central venous catheter

• Prior history of DVT or PE

Bedbound patients and patients undergoing surgical, especially orthopedic, procedures benefit, and most of these patients can be identified before a thrombus forms (see table Risk Assessment for Thrombosis Risk Assessment for Thrombosis

Choice of drug or device depends on various factors, including the patient population, the perceived risk, contraindications (eg, bleeding risk), relative costs, and ease of use. The American College of Chest Physicians has published comprehensive evidence-based recommendations for prophylaxis of acute DVT, including the duration of prophylaxis, in surgical and nonsurgical patients and during pregnancy (The American College of Chest Physicians most recent Guidelines on Prevention of Thrombosis) . The need for prophylaxis has been studied in numerous patient populations.

The type of surgery as well as patient-specific factors determine the risk of DVT. Independent risk factors include

• Age ≥ 60 years

• Prior DVT or PE

• Cancer

• Anesthesia ≥ 2 hours

• Bed rest ≥ 4 days

• Male sex

• Hospital stay ≥ 2 days

• Sepsis

• Pregnancy or the postpartum state

• Central venous access

• Body mass index (BMI) > 40

Drug therapy to prevent DVT is usually begun after surgery to help prevent intraoperative bleeding. However, preoperative prophylaxis is also effective.

In general surgery patients, low dose unfractionated heparin is given in doses of 5000 units subcutaneously every 8 to 12 hours for 7 to 10 days or until the patient is fully ambulatory. Immobilized patients not undergoing surgery should receive 5000 units subcutaneously every 8 to 12 hours until they are ambulatory.

Fondaparinux 2.5 mg sc once/day is as effective as low molecular weight heparin for orthopedic surgery and in some other settings. It is a selective factor Xa inhibitor.

Warfarin is usually effective and safe at a dose of 2 to 5 mg orally once a day or at a dose adjusted to maintain an INR of 2 to 3 in patients who have undergone total hip or knee replacement. It is still used by some orthopedic surgeons for prophylaxis in these patients but is increasingly being supplanted by the use of the direct oral anticoagulants.

Rivaroxaban, an oral factor Xa inhibitor, is used for prevention of acute DVT/PE in patients undergoing total knee or hip arthroplasty. The dose is 10 mg orally once a day. Its use in other patients (surgical and nonsurgical) is currently under investigation.

Apixaban, an oral factor Xa inhibitor, is also used for prevention of acute DVT/PE in patients undergoing total knee or hip arthroplasty. The dose is 2.5 mg orally twice a day. Like rivaroxaban, its use in other types of patients is currently under investigation.

Inferior vena cava filters, intermittent pneumatic compression (also known as sequential compression devices [SCD]), and graded elastic compression stockings may be used alone or in combination with drugs to prevent PE. Whether these devices are used alone or in combination depends on the specific indication.

An inferior vena cava filter (IVCF) may help prevent PE in patients with DVT in the leg, but IVCF placement may risk long-term complications. Benefits outweigh risk if a second PE is predicted to be life-threatening; however, few clinical trial data are available. A filter is most clearly indicated in patients who have:

• Proven DVT and contraindications to anticoagulation

• Recurrent DVT (or emboli) despite adequate anticoagulation

• Undergone pulmonary thromboendarterectomy

• Marginal cardiopulmonary function, causing concern for their ability to tolerate additional small emboli (occasionally)

Because venous collaterals can develop, providing a pathway for emboli to circumvent the IVCF, and because filters occasionally thrombose, patients with recurrent DVT or nonmodifiable risk factors for DVT may still require anticoagulation. An IVCF is placed in the inferior vena cava just below the renal veins via catheterization of an internal jugular or femoral vein. Most IVCFs are removable. Occasionally, a filter dislodges and may migrate up the venous bed, even to the heart, and needs to be removed or replaced. A filter can also become thrombosed, causing bilateral venous congestion (including acute phlegmasia cerulea dolens) in the leg, lower body ischemia, and acute kidney injury.

Intermittent pneumatic compression (IPC) with SCDs provides rhythmic external compression to the legs or to the legs and thighs. It is more effective for preventing calf than proximal DVT. It is insufficient as sole prophylaxis after hip or knee replacement but is often used in low-risk patients after other types of surgery or in medical patients who have a low-risk of DVT or who are at high risk of bleeding. IPC can theoretically trigger PE in immobilized patients who have developed occult DVT while not receiving DVT prophylaxis.

Graded elastic compression stockings are likely less effective than external pneumatic leg compression, but one systematic meta-analysis suggested that they reduced the incidence of DVT in postoperative patients from 26% in the control group to 13% in the compression stockings group.

After surgical procedures with a high incidence of DVT/PE, low dose unfractionated heparin, low molecular weight heparin, or adjusted-dose warfarin is recommended.

After orthopedic surgery of the hip or knee, additional options include the direct oral anticoagulants, rivaroxaban and apixaban. These drugs are safe and effective and do not require laboratory tests to monitor the level of anticoagulation as is needed for warfarin.

For total hip arthroplasty, patients should continue to take anticoagulants for 35 days postoperatively. In selected patients at very high risk of both DVT/PE and bleeding, temporary placement of an IVCF is an option for prophylaxis.

A high risk of DVT/PE also occurs in patients undergoing elective neurosurgery and those with acute spinal cord injury and multiple trauma. Although physical methods (SCDs and elastic stockings) have been used in neurosurgical patients because of concern about intracranial bleeding, low molecular weight heparin appears to be an acceptable alternative. The combination of SCDs and low molecular weight heparin may be more effective than either alone in high-risk patients. Limited data support the combination of SCDs, elastic compression stockings, and low molecular weight heparin in patients with spinal cord injury or in multiple trauma. For very high-risk patients, a temporary IVCF may be considered.

In acutely ill medical patients, low dose unfractionated heparin, low molecular weight heparin, or fondaparinux can be given. SCDs, elastic compression stockings, or both may be used when anticoagulants are contraindicated. For ischemic stroke patients, low dose unfractionated heparin or low molecular weight heparin can be used; SCD, elastic compression stockings, or both may be beneficial.