32: Peripheral Arterial Disease & Venous Thromboembolism

Peripheral vascular disease broadly defines any vascular disease of the extracranial carotid arteries, the aorta and its branches, and the extremities. However, peripheral arterial disease (PAD) is usually used to refer to atherosclerotic disease of the lower extremities. Atherosclerotic PAD is the most common form of PAD in older adults. But, the differential diagnosis for arterial vascular disease is quite broad (Table 32–1).

The prevalence of PAD is >10% in individuals older than age 60 years and increases to >25% in people older than 75 years. Although PAD is associated with cardiovascular risk factors, a prevalence of approximately 9% has been documented in patients without traditional risk factors. Nontraditional risk factors, including ethnicity, also influence disease prevalence. Current guidelines call for screening all individuals who are older than age 65 years, patients older than age 50 years with a history of smoking or diabetes, and individuals with suspected PAD, including exertional leg symptoms and nonhealing wounds.

There are 2 management issues in patients with PAD. Both are important to successful patient care. First is the need to adequately address underlying cardiovascular risk factors. Atherosclerosis is assumed to be a systemic process. Concomitant cerebrovascular or coronary disease has been demonstrated in up to 30% of patients. The second issue, which is usually more concerning to the patient, is the symptoms related to the vascular occlusive disease. Although most patients with PAD are asymptomatic or present with atypical lower-extremity symptoms, intermittent claudication, exertional muscle pain that is consistent in onset and rapidly relieved with rest, is the most common symptom clinically identified with PAD. A minority present with critical limb ischemia, including ulceration, tissue loss, or gangrene, and are at risk for limb loss.

Signs & Symptoms

Intermittent claudication (IC) is recognized as the hallmark of PAD. However, it may be difficult for patients to adequately describe the symptoms of IC. IC is caused by the inability of the arterial supply to meet the metabolic demands of the muscles. Symptoms have been described as muscle pain, cramping, fatigue, tiredness or even weakness associated with exertion. The symptoms should be reproducible with a constant workload and resolve within 5–10 minutes of rest. Most importantly, the symptoms do not occur at rest or with standing alone.

Most patients with PAD do not have symptoms of IC. Most are asymptomatic, have nonspecific lower-extremity exertional symptoms, or even have resting symptoms that are difficult to relate to PAD. In many cases, patients are asymptomatic because they have altered their lifestyle becoming more sedentary and/or eliminated symptom producing activities. Others have nonspecific lower-extremity symptoms, both with exertion and at rest, potentially related to comorbid musculoskeletal or neuropathic conditions.

Critical limb ischemia, with rest pain, nonhealing ulcers or tissue loss, or gangrene, is the most severe presentation of PAD. These patients are at risk for limb loss. Patients may complain of coldness, numbness, or pain in the foot or toes. This is especially troubling at night when the limb is elevated—so-called nocturnal rest pain. These patients may prefer to sleep in a chair or hang the limb over the bed side in an effort to improve blood flow and reduce the symptoms.

Skin changes, including loss of hair elements and dystrophic nail changes, are common but nonspecific findings. Dependent rubor followed by pallor or blanching of the extremity with elevation may be easily assessed in the office. The feet should be regularly inspected at office visits for ulcers between the toes—so-called “kissing ulcers”—and ulcers related to ill-fitting footwear. Ulceration in PAD is a particularly ominous sign because many of these patients ultimately require revascularization for healing.

Pulse examination should include both palpation and grading of the peripheral pulses. Pulses are graded as absent (grade 0), present but diminished (grade 1), normal (grade 2) or bounding (grade 3). In addition to the routine palpation and inspection of the feet, patients should be examined for vascular disease involving other vascular beds. Blood pressure should be recorded in both arms. The higher of the 2 extremities should be used for monitoring hypertension and medication titration. The aorta, carotid and femoral arteries should be auscultated for the presence of bruits. The aorta should be palpated for the presence of an abdominal aortic aneurysm. However, the absence of a bruit or inability to palpate the aorta does not exclude disease. Coexistent compromise in cardiopulmonary function, neuropathy, arrhythmia, and severe anemia should be identified as these conditions may negatively impact PAD-related outcomes.

Laboratory Findings

There are no laboratory markers to identify patients with atherosclerotic PAD. Patients with PAD should have a fasting lipid profile to assist in the management of dyslipidemia. Fasting blood glucose or hemoglobin A1c monitoring for detection and treatment of diabetes should occur. Laboratory evaluation to exclude other nonatherosclerotic vascular disease (see Table 32–1) should be performed as indicated. This may include complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and a complete metabolic panel (CMP).

Diagnostic Testing

Along with pulse assessment, patients with a clinical suspicion of PAD should have baseline evaluation of their perfusion. The ankle-brachial index (ABI) can be used to determine the presence and severity of perfusion (Table 32–2). An ABI <0.91 is considered abnormal. The current American College of Cardiology and American Heart Association (ACC/AHA) guidelines recommend ABI measurement in patients with exertional leg symptoms suspicious for PAD, who have nonhealing wounds and are older than age 65 years. In patients with calcified arteries caused by advanced age, diabetes, renal disease, or other processes, the ABI will be inaccurate and the toe-brachial index (TBI) should be used. A TBI <0.7 is consistent with PAD.

The ABI is a ratio of systolic arterial pressures recorded in the upper and lower extremities. It can easily be performed in the office or by a vascular laboratory. The required equipment includes a continuous-wave handheld Doppler and a blood pressure cuff. To perform an ABI, the blood pressure cuff is placed sequentially over both upper extremities followed by both lower extremities. With the handheld Doppler positioned sequentially over the brachial, dorsalis pedis (DP) and posterior tibial (PT) arteries, the blood pressure cuff is inflated to suprasystolic pressure and then slowly deflated. The pressure at which the systolic signal is audible is recorded. The ABI is calculated by dividing the highest pressure of the limb, either the DP or PT, by the highest the brachial pressure.

Exercise ABI testing should be performed when patients have symptoms consistent with IC but a normal resting ABI. Standardized protocols are used and the patient must be able to safely walk on a treadmill without assistance. A history of significant cardiopulmonary disease, nonhealing ulcers or critical limb ischemia, and gait abnormalities are contraindications for exercise testing.

Additional Testing

When intervention is considered for lifestyle-limiting symptoms or for critical limb ischemia, additional testing to determine the anatomical level of disease and plan for revascularization is warranted. Segmental arterial limb pressures (SLP) and pulse volume recording (PVR) with or without exercise testing can localize disease as well as provide hemodynamic information. Arterial duplex ultrasound may also be used to localize disease. Duplex imaging provides anatomic information regarding stenosis, occlusion, and calcification within the atherosclerotic lesions. The use of ultrasound avoids contrast and radiation associated with other angiographic imaging. Angiographic imaging, including computed tomographic angiography (CTA), magnetic resonance angiography (MRA), and conventional digital subtraction angiography (DSA), are not diagnostic tools but are used to determine the anatomic levels of disease and plan surgical or endovascular revascularization.

Patients will not typically complain of lower-extremity pain with ambulation. Many patients attribute leg pain to arthritis or part of the aging process. The differential diagnosis of exertional leg symptoms may be quite broad, including a variety of musculoskeletal, neurogenic, and inflammatory conditions. A thorough history, including questions to determine the timing, onset, exacerbating and relieving factors, and a complete physical examination, can help distinguish PAD and IC from other vascular and nonvascular causes of lower-extremity exertional symptoms. It can be difficult to distinguish IC from pseudoclaudication or neurogenic claudication (Table 32–3). History demonstrating variability of the symptoms, symptom onset at rest or with standing, and the improvement when walking with a shopping cart or when bending forward, increases suspicion for neurogenic pseudoclaudication. PAD and other vascular disorders causing lower-extremity ischemia are included in the differential diagnosis of IC (see Table 32–1).

General Considerations

Good skin and foot care should be recommended. Minor trauma may be associated with a limb or life-threatening event in patients with PAD. Diabetic patients should have routine podiatric nail care. Daily foot inspection should also be reinforced. Shoe gear and devices to offload pressure points and boney prominences are recommended. Patients who are hospitalized, in a nursing home, or otherwise immobile are prone to pressure injury and should be protected.

Cardiovascular Risk Reduction

The Reduction of Atherosclerosis for Continued Health (REACH) registry has confirmed the undertreatment of risk factors in PAD, as well as the risk for primary and recurrent cardiovascular events in this at-risk population. Aggressive cardiovascular risk factor modification is required to slow the progression of PAD and decrease future cardiovascular and cerebrovascular morbidity and mortality. Patients should be treated to achieve risk-reduction goals similar to patients with diagnosed coronary artery disease.

Patients should be advised to stop smoking, and offered counseling or pharmacologic therapy. Blood pressure should be treated to a target of <140/90 mm Hg or <130/80 mm Hg with diabetes or chronic kidney disease. β Blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics should be included in the antihypertensive regimens. Diabetes should be managed to maintain a HbA1c (glycosylated hemoglobin) approximately 7% in an effort to reduce microvascular complications. Lipid-lowering regimens should include a “statin” to lower low-density lipoprotein (LDL) to <100 mg/dL. All patients should be on antiplatelet therapy. Aspirin 75–325 mg daily is recommended. In aspirin-intolerant individuals, clopidogrel 75 mg daily should be considered.

Exercise Therapy

A dedicated walking program can improve pain-free walking distance and maximal walking distance. Supervised exercise programs are more beneficial than self-directed programs. Unfortunately, these programs are not widely available or accessible. Motivated patients certainly benefit from self-directed walking programs. Patients should be instructed to perform a minimum of 3 walking sessions weekly. They should walk at a pace to induce symptoms within 5 minutes. After symptom onset, they should rest until the symptoms abate and then resume walking. Each exercise session should last for 30–45 minutes using walk-rest-walk cycles. Most patients will see improvement in their walking capacity within 4 to 8 weeks of participation and significant benefits are usually obtained by 12 to 26 weeks. Patients should be advised that acquired benefits are quickly lost once they stop exercising.

Pharmacotherapy

Two drugs are FDA approved for symptomatic patients with IC: cilostazol and pentoxifylline. Cilostazol is a phosphodiesterase 3 inhibitor. The mode by which it improves walking performance in IC is not well understood. The usual dose for cilostazol is 100 mg twice a day. Cilostazol is contraindicated in patients with a history of heart failure. Frequent side effects include headache, palpitations, feeling lightheaded or dizzy and gastrointestinal effects including nausea and diarrhea. These are more common in older adults. Most side effects are self-limited or are better tolerated by initiating therapy at a reduced dose and escalating to full therapy. A 50-mg tablet is available for dose reduction.

Pentoxifylline is a hemorrheologic agent thought to improved red blood cell distensibility. The usual dose is 400 mg 3 times daily. Although there are few side effects associated with pentoxifylline it also has not demonstrated consistent benefit for patients with IC.

For either drug, if clinical improvement is not realized after 26 weeks of therapy, the drug should be discontinued as polypharmacy may be a concern and several other drugs, such as statins, antiplatelet agents, and antihypertensives, are often prescribed concomitantly in this population. Neither cilostazol nor pentoxifylline affect the mortality associated with underlying cardiovascular risk.

Revascularization

Revascularization is indicated in patients with critical limb ischemia and may be considered in those limited by IC despite optimal medical therapy and participation in an exercise regimen. Angiography, MRA, or CTA is used to determine the optimal revascularization strategy. In patients with critical limb ischemia, including rest pain, ischemic ulceration, or gangrene, revascularization may be limb saving. For patients with IC, revascularization is generally elective.

A complete discussion of revascularization is beyond the scope of this chapter. The tools, strategies, and options for revascularization continue to evolve. Operators and patients alike usually prefer endovascular procedures to surgical management. Today, more patients are candidates for less-invasive procedures. The options and choice for revascularization should be individualized to each patient. Whether endovascular or surgical revascularization is planned, the risks, benefits, and alternatives for each procedure should be thoroughly and candidly discussed with the patient.

As mentioned, the overwhelming risk to patients with PAD is the morbidity and mortality associated with secondary cardiovascular and cerebrovascular events. The overall limb prognosis in PAD is good. Approximately 75% of patients with IC remain stable or will improve under the influence of pharmacotherapy and exercise. Only approximately 25% of patients will deteriorate with respect to walking capacity. A minority of these patients will require an intervention or surgery to improve walking capacity. Less than 4% of patients will suffer limb loss. Most of these patients will be diabetic or continue to smoke.

General Principles in Older Adults

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third leading cause of cardiovascular death in the United States. More than 400,000 deaths annually are attributed to VTE. VTE risk increases with age. VTE risk for patients older than age 70 years is approximately 1% per year. Table 32–4 lists the inherited and acquired risk factors for VTE. Despite a known association between VTE and inherited thrombophilias, testing for these disorders is rarely indicated in geriatric patients. Patients with idiopathic VTE, without an identifiable etiology, should undergo age- and gender-appropriate cancer screening. Following a complete history, physical examination, and basic laboratory testing, additional testing using CT scans, bronchoscopy, bone marrow evaluation, and other evaluations are used to investigate underlying abnormalities.

Clinical Findings

Signs & Symptoms

The signs and symptoms of VTE are nonspecific. Therefore, a clinical diagnosis is not acceptable. Patients may present with nonspecific constitutional, limb or cardiopulmonary complaints. High clinical suspicion and imaging is required to exclude VTE.

Up to 50% of DVTs are asymptomatic. Clinical symptoms include limb pain, swelling, erythema, and increased warmth. Superficial thrombophlebitis may present with localized erythema and tenderness associated with a palpable superficial venous cord. The Homan sign—pain on squeezing the calf or with passive dorsiflexion of the foot—is commonly referred to and noted on examination. However, it lacks sensitivity or specificity for diagnosing DVT and is unreliable for clinical diagnosis.

The symptoms of PE are equally nonspecific. Patients may present with tachycardia and tachypnea without associated complaints. When present, chest pain may be pleuritic in nature. Dyspnea, cough, near syncope, and palpitations are common. Hemoptysis is uncommon and usually associated with pulmonary infarction. Syncope is a common admitting complaint and PE is frequently overlooked in the differential diagnosis, leading to delays in diagnosis and management.

Laboratory Findings

No laboratory test is specific to diagnosis VTE. In the appropriate clinical setting, a negative D-dimer may be used to exclude VTE from the differential diagnosis. D-dimer is frequently positive following surgery, trauma, hospitalization, pregnancy, and in older adults. Therefore, it is best utilized in the outpatient ambulatory setting in patients at low-risk for VTE. A positive D-dimer is not helpful.

VTE patients should have CBC, CMP, and urinalysis performed to identify underlying disorders associated with VTE. Abnormalities on the initial laboratory testing should be used to direct additional testing or imaging that may be warranted. Antiphospholipid antibody testing may be helpful in the geriatric population. Testing for lupus anticoagulant and anticardiolipin antibodies may influence the duration of therapy and the choice of anticoagulation. Testing for other thrombophilias is less likely to be helpful. Protein C, protein S and antithrombin deficiency testing are virtually never warranted in older adults.

Patients with acute PE should have biomarker assessment, including troponin and BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal pro brain natriuretic peptide), to look for evidence of myocardial injury. Both troponin and BNP, when normal, have a high negative predictive value for in-hospital and 30 days postdischarge mortality. When the biomarkers are normal they may be used to risk stratify patients for accelerated hospital discharge.

Diagnostic Testing

Venography is rarely required, but remains the gold standard for diagnosing DVT. Duplex ultrasound has become the test of choice to diagnose or exclude DVT. It is widely available, noninvasive, and well tolerated. Duplex ultrasound relies on the inability to completely compress the lumen of the vein using externally applied pressure. Intraluminal echogenicity is less specific for DVT. Secondary changes in the venous waveforms are also evaluated. Normal waveforms are phasic with respiration and augment with calf compression. The failure to augment or loss of phasicity, monophasic waveforms, may indicate proximal obstruction. Only venous segments that are adequately visualized can be assessed for DVT. This is a limitation that is frequently misunderstood. If a venous segment is not fully evaluated, DVT cannot be excluded. The sensitivity and specificity of duplex ultrasound for DVT diagnosis are approximately 98%. If there is negative testing but high clinical suspicion, especially for iliac, inferior vena cava (IVC), or calf vein DVT, repeat duplex imaging in 5–7 days is likely warranted.

Computed tomography venography (CTV) and magnetic resonance venography (MRV) may be used for diagnosis especially when imaging the IVC and pelvic veins. CTV can easily be added to CT PE imaging. This does not require additional contrast but the radiation exposure is significant. MRV does not use radiation and does not always require contrast. It may be helpful in evaluating patients with acute and chronic DVT. However, imaging may not be readily available and claustrophobia may limit some patient’s ability to perform testing. CTV and MRV may be used as an alternative to venography to confirm the diagnosis of DVT when duplex imaging is nondiagnostic.

Up to 50% of patients with DVT may have clinically asymptomatic PE. Clinical suspicion for PE should prompt appropriate testing. Chest x-ray may be normal and is frequently nonspecific. When abnormal, findings of volume loss, atelectasis, effusions, or infiltrates predominate. Classically described Westermark sign (focal oligemia), Hampton hump (wedge-shaped pleural based density), and pulmonary artery enlargement are uncommon. Electrocardiogram findings are also frequently nonspecific. The most common finding is sinus tachycardia. The classically described S₁Q₃T₃ changes may be seen with large PE and right ventricular strain.

Computed tomography pulmonary angiogram (CTPA) is the most widely available and commonly used test for diagnosing PE. It is readily available and well tolerated. PE is diagnosed as an intraluminal filling defect within the pulmonary arteries. With advanced technology, scanners can complete imaging to the level of the subsegmental pulmonary arteries in a single breathhold. It requires contrast and may be limited in patients with renal insufficiency. Timing of the contrast bolus is essential, and in some patients may limit the sensitivity and specificity of the examination, especially for more peripheral emboli. CTPA can also be used to evaluate for radiographic signs of right heart strain associated with large PE. A right ventricle to left ventricle ratio >0.9 measured on a 4-chamber view is consistent with right-heart strain.

Ventilation-perfusion (V/Q) lung scanning is still used to diagnose of acute PE. However, in many centers availability is limited. The testing should be performed in the setting of a normal chest x-ray and when there is high clinical pretest probability for PE. Nondiagnostic intermediate or indeterminant scans are common. Only scans that are read as normal or near normal or high probability are helpful to exclude or diagnose PE.

Pulmonary angiography remains the gold standard for diagnosing PE, although it has been essentially replaced by CTPA imaging. The contrast and radiation exposure are similar and CTPA is less invasive. If CTPA imaging is nondiagnostic and there is a need to diagnose or exclude PE then angiography is the test of choice. Despite widely held beliefs that angiography is too invasive to use regularly, complications related to angiography are infrequent.

Echocardiography is not a diagnostic test for PE although echocardiographic information may be helpful to risk-stratify patients for thrombolytic therapy or for accelerated hospital discharge. Echocardiography is used to evaluate right-heart dysfunction. Right-heart strain portends a worse in-hospital outcome compared to patients without evidence for right ventricle volume overload. Findings on echocardiogram include right ventricle dilation, septal flattening or deviation toward the left ventricle, tricuspid regurgitation, and elevated right ventricle systolic pressure.

Differential Diagnosis

Unilateral leg pain, erythema and swelling are common symptoms. Within the differential diagnosis one must consider superficial thrombophlebitis, popliteal cyst with or without rupture, traumatic injury such as a sprain or ruptured calf muscle, cellulitis, and acute inflammation associated with chronic venous insufficiency (CVI). In patients with a low pretest clinical probability, a negative D-dimer excludes DVT and eliminates the need for additional testing.

The signs and symptoms associated with PE are also nonspecific. Other cardiopulmonary, vascular and inflammatory etiologies must be excluded. Included in the differential diagnosis are myocardial injury, pericarditis, congestive heart failure, pneumonia, pleuritis, pneumothorax, aortic dissection, and musculoskeletal sprain, strain, or contusion.

Complications

The risk of postthrombotic syndrome (PTS) after DVT is significant. Many patients develop symptoms within 2 years following the initial event. Extensive DVT and recurrent events increase PTS risk. The use of compression stockings for 2 years following DVT may decrease this risk by up to 50%. A minority of patients (<5%) will develop chronic thromboembolic disease (CTED) after PE. There are no clinical factors, biomarkers, or other strategies to determine which patients are at risk. Patients presenting with progressive dyspnea or right-heart dysfunction following PE should be evaluated for CTED.

Treatment

General Considerations

Anticoagulation is the mainstay of treatment for VTE. Appropriate therapy should be started when the diagnosis of VTE is considered. In patients at low risk for complications from anticoagulation, data collection and diagnostic testing should not delay the initiation of anticoagulation. Intravenous unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux are appropriate initial therapies for VTE.

Patients with DVT without signs or symptoms of PE can frequently be treated either solely or at least partially as an outpatient. Arranging home therapy, self-injection teaching and patient education required staff time and dedication but many patients are able to successfully perform the necessary tasks. Clinically stable patients with PE can frequently be assessed using echocardiography and biomarkers such as troponin and BNP. When normal, patients can be treated either inpatient or using an accelerated discharge plan. Close clinical follow up after discharge should be arranged for all VTE patients.

Patients with a contraindication to anticoagulation should be managed by IVC filter insertion. However, appropriate anticoagulation should be initiated once the anticoagulation risk has resolved.

Pharmacotherapy

UFH should be administered using weight-based bolus and infusion dosing. The activated partial thromboplastin time (aPTT) or anti-Xa assay should be titrated to keep the patient within the appropriate therapeutic range. It is important to recognize that the aPTT therapeutic range is institution specific and awareness of local protocols is necessary. In patients in whom thrombolysis may be considered, UFH is the drug of choice because of its short half-life and the ability to easily monitor therapy.

LMWHs provide the opportunity for once- or twice-daily dosing. Ease of administration also facilitates accelerated discharge or home therapy for appropriate patients. The available LMWHs are all renally excreted. Dose adjustment or avoidance is required with creatinine clearance <30 mL/min. Monitoring with LMWH specific anti-Xa assay may be prudent in patients with borderline renal function, with low body mass, or the morbidly obese. The assay must be drawn 4 hours after the dose. A target LMWH anti-Xa between 0.6 and 1.0 is appropriate for q 12 hour dosing, whereas a target of 1.0–2.0 is appropriate for daily dosing regimens. Patients who develop VTE in the setting of an underlying malignancy are best managed with LMWH monotherapy for the initial 3–6 months of treatment. Patients can then be reassessed for continuing LMWH or switching to warfarin therapy for the duration of their treatment.

Fondaparinux is a pentasaccharide molecule approved for treating both DVT and PE, when therapy is initiated in the hospital. Dosing is weight based. Patients who weigh <50 kg should receive 5 mg daily; who weigh 50–100 kg should be dosed at 7.5 mg daily; and who weigh >100 kg should receive 10 mg daily. Monitoring is not used. Fondaparinux is renally excreted. It should be used cautiously with renal insufficiency and is not appropriate with a creatinine clearance <30 mL/min. The half-life is approximately 17 hours. The drug should be avoided when there is a need for intervention or a high risk of bleeding. There is no antidote to reverse the effects of fondaparinux.

Warfarin remains the long-term drug of choice for most patients. In general, the first dose of warfarin may be started on the day of admission. Warfarin, a vitamin K antagonist, interrupts the terminal carboxylation of vitamin K-dependent proteins. Therefore a minimum 4–5 day overlap between the parenteral drug and warfarin is required to ensure the premade vitamin K-dependent proteins have been adequately depleted. For most patients, the target international normalized ratio (INR) is 2.5, with an acceptable range being between 2 and 3. After the minimum 4–5-day overlap, the INR should be >2 on 2 consecutive days before stopping the parenteral drug and maintaining warfarin therapy.

An oral direct thrombin inhibitor, dabigatran, and oral anti-Xa agents, rivaroxaban and apixaban, have been studied in VTE, but are not yet approved. Potential advantages of these agents are the once- or twice-daily oral administration. These drugs do not require monitoring. The major disadvantage with these agents is a lack of an antidote for easy reversal.

Intervention

Patients with extensive DVT or massive PE who are unstable at the time of admission should be assessed for thrombolysis. The use of pharmacomechanical thrombolysis (PMT) or catheter-directed thrombolysis (CDT) are not confined to patients with phlegmasia cerulean dolens or venous gangrene. Patients with extensive DVT may benefit from PMT to help clear the thrombus in an effort to preserve valve function, improve mobility, and decrease symptoms associated with the acute DVT. PMT is not appropriate for all patients with DVT but especially with iliofemoral DVT consideration for PMT should be entertained.

Patients with massive unstable PE should also be considered for thrombolysis; either systemic infusion or catheter based therapies. Patients with submassive PE with significant cardiopulmonary dysfunction may be appropriate for thrombolytic therapy but the bleeding risks may outweigh the benefits in these patients. The risk for major bleeding in thrombolysis is approximately 15%. The risk for intracranial bleeding is often cited as 1% to 2%. Bleeding risk is increased in patients older than age 70 years. Recent surgery or trauma, gastrointestinal bleeding, uncontrolled hypertension, and recent stroke are contraindications to thrombolysis.

IVC filter insertion is appropriate in patients with a contraindication to anticoagulation or in whom anticoagulation is complicated by bleeding or thrombosis despite adequate therapeutic anticoagulation. Many IVC filters deployed today are used for relative indications, including underlying cardiopulmonary disease, significant PE, free floating DVT visualized on duplex ultrasound, and patients at high risk for noncompliance with anticoagulation. It is important to realize that IVC filters help manage patients with DVT and prevent massive PE. However, IVC filters do not treat DVT and anticoagulation is required to stop propagation of the DVT, prevent recurrent DVT as well as prevent embolism. Once the absolute or relative risk for anticoagulation has resolved appropriate anticoagulation should be initiated. Patients with an optionally retrievable IVC filter should be assessed for filter retrieval prior to stopping anticoagulation. There is sufficient data to suggest that retained filters may contribute to subsequent DVT. Once they are no longer required, they should be removed if possible.

Additional Considerations

Bed rest is frequently advised in DVT or PE; this is actually detrimental to recovery. Studies demonstrate that ambulation is not associated with increased risk for PE but does improve venous patency. Clinically stable patients should be encouraged to ambulate while hospitalized and return to normal activities after discharge.

Compression is recommended for patients with DVT. The risk of PTS approaches 70% following DVT. Ideally, patients should be prescribed knee-high stocking with a minimum of 20–30 mm Hg compression before discharge. For patients undergoing PMT or with extensive DVT and more severe symptoms, 30–40 mm Hg compression is recommended.

Duration of Therapy

The optimal duration of therapy for VTE is unknown. Decisions regard continuing or discontinuing anticoagulation should take into account the underlying etiology of the VTE, patient comorbidities, patient preference for anticoagulation, and the estimated risk for recurrence. In general, a situational event following surgery, hospitalization, or other limited risk factors should be treated a minimum of 3 months and until the attributable risk factor is no longer present. Patients with idiopathic VTE require a minimum of 6–12 months of initial anticoagulation. Patients with recurrent VTE, underlying high-risk thrombophilias, or cancer likely require indefinite therapy. However, to determine the optimal duration of therapy, the benefits of anticoagulation need to be weighed against the risk.