Susan M. Begelman MD, RVT
PERIPHERAL ARTERIAL DISEASE
ESSENTIALS OF DIAGNOSIS
The majority of elderly patients with peripheral arterial disease (PAD) have underlying atherosclerosis. As a result, patients with PAD have a high risk of cardiovascular and cerebrovascular morbidity and mortality. The prevalence of peripheral arterial disease rises rapidly with age. Although present in >20% of people who are 75 or older, PAD is diagnosed by <30% of primary care physicians.
Clinical manifestations of the disease vary. The majority of patients are asymptomatic. This may reflect the presence of limited disease or, more commonly in inactive patients, diminished capacity for ambulation that is necessary to produce intermittent claudication. PAD can also manifest as critical limb ischemia. In general, symptom severity increases with the number and length of stenotic lesions in the limb.
Risk factor modification is necessary to slow or halt progression of peripheral arterial disease and decrease the risk of cardiovascular and cerebrovascular death. Goals of therapy include cigarette smoking cessation, lowering blood pressure to <140/90 mm Hg (<135/85 in high-risk patients), improving glucose control with a target HbA1c <7.0%, and lipid lowering with a target low-density lipoprotein <100.
Good skin and foot care is essential. Many nonhealing ulcers begin with minor trauma. Therefore, patients with significant PAD should be encouraged to have a health care professional trim their toenails. Similarly, nursing home patients and individuals who have limited mobility are prone to pressure ulcers, which can become gangrenous. Regular use of devices that protect the heels can prevent unnecessary tissue or limb loss.
Many patients are asymptomatic. Mild to moderate PAD can produce lower extremity discomfort with ambulation known as intermittent claudication. The pain is often described as an ache or “charley horse” in the calf, buttock, or thigh after a fixed distance of activity. Limb discomfort is usually relieved within minutes of activity cessation. Although some individuals will prefer to sit, most will achieve pain relief just by standing in place.
Disease progression or multiple stenotic lesions can result in rest pain (constant ischemic pain) and eventually nonhealing ulcers or gangrene. This is referred to as critical limb ischemia. Patients may have difficulty sleeping because of the constant pain and will prefer to keep the ischemic limb in a dependent position if possible. Neuropathic pain characterized by numbness and burning is seen in some patients with prolonged, severe ischemia (ischemic, monomelic neuropathy).
Skin changes are usually not present until significant PAD develops. Trophic changes, including cool, dry, shiny skin, hair loss, and thickened nails, are common but nonspecific findings. The limb can become edematous if kept dependent. Buerger's sign (also called Ratchow's sign) is the presence of rubor with limb dependency and rapid blanching with elevation. Ulcers and gangrene can develop at the tips of the toes, between 2 toes (“kissing ulcers”), and on pressure points.
A full cardiovascular examination is required to detect atherosclerosis in other arterial beds. One should record the blood pressure in both arms, the presence of carotid, aortic, and femoral artery bruits, murmurs, and
the size of the abdominal aorta to exclude an aneurysm. Evidence of arrhythmias, poor cardiac output, pulmonary disease, and anemia are important to note because their presence can worsen lower extremity symptoms. Most important, a complete pulse exam includes the carotid, radial, ulnar, femoral, popliteal, dorsalis pedis, and posterior tibial pulses. They should be graded as 0 (absent), 1 (diminished), or 2 (present).
Blood tests cannot be used to diagnose peripheral arterial disease, but several studies should be ordered to detect potential risk factors and comorbid diseases that may exacerbate symptoms. A complete blood count with a platelet count will reveal anemias, polycythemia, and thrombocytosis. A baseline platelet count should be drawn before exposing an individual to unfractionated heparin during the course of therapy (eg, an endovascular intervention). A fasting blood glucose level, hemoglobin A1c, urinalysis for protein and glucose, blood urea nitrogen, and creatinine can detect occult diabetes mellitus and long-standing hypertension. Renal function testing is also indicated before angiography. A fasting lipid profile should be checked. Infrequently, elderly patients will not have typical risk factors for atherosclerosis. An erythrocyte sedimentation rate to screen for vasculitis and hypercoagulable testing, including homocysteine levels, may be indicated in patients with a history of thrombosis.
An ankle-brachial index (ABI) can easily be performed in an office setting to screen for PAD using a blood pressure cuff and a hand-held Doppler. The ABI is calculated by dividing the higher of the dorsalis pedis and posterior tibial systolic pressures for an individual leg by the higher of the two brachial pressures. An ABI <0.9 is abnormal. Most patients with critical limb ischemia will have an ABI of <0.4. Calcified, noncompressible arteries can be found in patients who are elderly and have diabetes mellitus, chronic renal failure, or a history of chronic steroid use. An ABI >1.3 is unreliable. A toe-brachial index may be useful in this situation and can be performed in a vascular laboratory.
Full physiological testing includes pulse volume recordings (PVR), segmental limb pressures (SLP), and an ABI. In addition to assessing disease severity, these studies can help determine the location of disease and the likelihood that an ulcer will heal. Exercise stress testing (walking on a treadmill) increases the sensitivity of physiological testing by magnifying pressure gradients or producing them when an individual has a normal study at rest. Stress testing is contraindicated in patients with significant cardiopulmonary disease, rest pain, nonhealing ulcers, and unsteady gait requiring a cane or walker for support.
Arterial duplex ultrasonography can be used to assess an individual's anatomy, not functional status. However, velocity gradients across stenotic lesions can be measured. An ultrasound study has the greatest clinical utility when used in conjunction with physiological testing to plan an endovascular intervention. It may be the only test available in some centers, so its limitations must be recognized. Magnetic resonance imaging can also be used to confirm the diagnosis of PAD. Like ultrasonography, it cannot directly assess functional status. In addition, this modality may not reliably differentiate between a tightly stenotic lesion and an occluded one. Except in rare circumstances, an angiogram is not necessary to diagnose PAD and should be performed only when an intervention is planned.
Comprehensive history and physical examinations are necessary to distinguish intermittent claudication from other causes of leg pain with ambulation, collectively known as pseudoclaudication (Table 21-1). The most common causes of pseudoclaudication are osteoarthritis of the spine causing spinal canal stenosis, osteoarthritis of the hip or knee, peripheral nerve pain, including sciatica and diabetic neuropathy, and venous claudication. The diagnosis of PAD might be delayed when older patients attribute their symptoms to arthritis or old age or when there is more than 1 cause for their leg pain.
In the absence of typical atherosclerotic risk factors, other diseases such as giant cell arteritis and remote trauma or radiation should be considered. Thrombosis of a popliteal artery aneurysm and primary vascular tumors are rare causes of intermittent claudication. Although atheroembolic disease can cause intermittent claudication, more commonly patients have rest pain, ischemic digits, and intact pedal pulses. Livedo reticularis may be present.
In addition to risk factor modification, patients with PAD, irrespective of their symptoms and disease severity, should be prescribed an antiplatelet agent to decrease the risk of cardiovascular and cerebrovascular events. However, aspirin (81–325 mg/day) and clopidogrel (75 mg/day) have not been shown to improve peripheral arterial disease or its associated symptoms. The decision to use either antiplatelet agent alone or in combination is often determined by cost and the patient's risk of bleeding.
Table 21-1. Clinical characteristics of claudication versus pseudoclaudication.
A regimented walking program can significantly increase pain-free walking distance and maximal walking distance in patients with intermittent claudication. The program consists of 3-4 sessions a week, each lasting 30-60 min, during which time the individual walks on a flat surface until developing maximal pain tolerable. A rest period is then taken until the pain resolves and ambulation can be resumed. Long-term participation is required to derive and sustain the program's benefits. More improvement is often seen in a supervised exercise rehabilitation program.
The 2 drugs available, pentoxifylline and cilostazol, are indicated for the reduction of symptoms from intermittent claudication but have not been shown to affect mortality. Only modest improvement in symptoms has been reported in some patients using pentoxifylline (400 mg 3 times a day with meals). A more impressive response has been demonstrated with cilostazol use (100 mg twice a day without food). Cilostazol, a phosphodiesterase inhibitor, is contraindicated in patients with congestive heart failure of any severity.β-Blockers rarely worsen symptoms and should not be withheld in most patients who require them.
Angiography is indicated when an endovascular intervention, a percutaneous angioplasty (with or without stent placement), or surgery is anticipated. The clinical indications for angiography are critical limb ischemia and lifestyle-limiting intermittent claudication. In frail patients with intermittent claudication, an assessment should first be made of the individual's ability to perform activities of daily living and quality of life. Elective angiography is warranted if the patient is limited in daily activities or the quality of life is affected by symptoms. However, for patients with critical limb ischemia aggressive intervention is required for tissue or limb salvage.
Endovascular intervention is the treatment of choice for short iliac artery stenoses. This approach is often used to fix longer iliac lesions and unilateral iliac occlusions. Single long lesions, short but heavily calcified stenoses, or multiple short stenoses in the superficial femoral and popliteal arteries (excluding the distal segment) are frequently treated with an endovascular intervention. Angioplasty is also used to improve proximal blood flow before surgery.
Individuals with PAD not amenable to an endovascular intervention should be evaluated for surgery. Every patient may not be a surgical candidate, and in the case of intermittent claudication, the decision to have surgery is elective. The length of the lesion, the arterial segment involved, the status of the inflow and distal runoff vessels, and the availability of autologous vein determine the surgical approach. In general, 5-year primary patency rates for aortoiliac reconstruction, infrainguinal bypass using autologous vein, and infrainguinal bypass using prosthetic material are >80%, 70%, and 40% respectively.
Approximately 25% of patients with intermittent claudication will deteriorate; however, of those, only 20% will require an intervention. Less that 2% of all patients with PAD will ultimately require an amputation (many of these patients have diabetes mellitus or continue to smoke). However, PAD is associated with significant mortality. More than half of patients with PAD will die from coronary artery disease, nearly 20% from strokes, and an additional 10% from ruptured abdominal aortic aneurysms.
CHRONIC VENOUS INSUFFICIENCY
ESSENTIALS OF DIAGNOSIS
The venous system consists of deep veins, perforating (communicating) veins, and superficial veins (the largest of which are the saphenous veins). Chronic venous insufficiency (CVI) results when there is valvular incompetency causing reflux, obstruction preventing outflow, or both. There are primary and secondary forms of venous insufficiency. Congenital CVI is rare and usually detected during childhood. Other causes of chronic venous insufficiency should be excluded before diagnosing primary valvular incompetency.
Secondary causes of CVI are common and include multiple past pregnancies, trauma, obesity, occupations requiring prolonged standing, and leg dependency. Patients who are wheelchair bound or who have limited mobility are especially at risk for venous insufficiency. Postthrombotic syndrome resulting from direct damage of the veins or incomplete vein recanalization is a form of CVI that occurs in patients who have had a deep vein thrombosis (DVT). Vein obstruction can occur when a popliteal artery aneurysm, pelvic mass, or adenopathy compress an adjacent vein. Vein stenosis from prior instrumentation, vascular tumors, and retroperitoneal fibrosis should be considered when a cause has not been identified.
Early institution of treatment prevents deterioration of symptoms and formation of ulcers.
Edema usually develops slowly and initially involves only the ankle, sparing the dorsum of the foot. Typically, the skin is soft and the edema is described as “pitting.” There may be minimal or no swelling early in the morning, but the edema progresses throughout the day. Constant swelling may be present in individuals who sleep in a chair or with their feet in a dependent position. Over time, the edema can progress more proximally, remain despite leg elevation, and no longer pit because of subcutaneous fibrosis.
Large varicose veins, prominent reticular veins, and multiple telangiectasias (spider veins) appear with superficial vein involvement. Incompetency at the level of the saphenofemoral junction can be detected by palpation over the area while the patient performs a Valsalva maneuver. Patients with CVI complain of pain, which is often described as a heaviness, tightness, or ache. Symptoms are more pronounced with prolonged standing and are usually relieved shortly after elevating the limb. Venous claudication, the sudden onset of “bursting” pain in the calf with ambulation, may occur in patients with significant venous obstruction.
The skin is often dry, shiny, and atrophic with a reddish, cyanotic hue when the limb is dependent. However, the limb is warm, not cool, as it is with arterial insufficiency. Eczematous dermatitis, hyperpigmentation caused by hemosiderin deposits, and ulceration, either spontaneous or resulting from minor trauma is seen in advanced stages of disease. Stasis ulcers are typically painless and often form just proximal to the medial malleolus.
Although the diagnosis of CVI can usually be made clinically, a venous duplex ultrasonogram is helpful in identifying incompetent veins segments in both the deep and superficial systems. Ascending venography can differentiate primary from secondary disease, whereas descending venography identifies the location and competency of individual valves.
Not all patients with leg edema have chronic venous insufficiency. The presence of end-organ dysfunction
must be excluded. History and physical examination is often sufficient to detect cirrhosis, congestive heart failure, cardiac valve disease, renal insufficiency, nephrotic syndrome, Cushing's disease, thyroid disorders, protein-losing enteropathies and other causes of malabsorption, and pulmonary hypertension.
Many medications prescribed to older patients are associated with edema formation. Common culprits include antihypertensive medications, especially the dihydropyridines, nonsteroidal anti-inflammatory drugs, steroids, and hormones (estrogen, progesterone, and testosterone). A class of oral antidiabetic drugs, the thiazolidinediones, can cause significant leg edema in a dose-dependent manner. Swelling has also been reported in patients with Parkinson's disease taking pramipexole.
Limb pain and ulceration account for the significant morbidity of this disease. Ulcer care requires frequent physician visits, and wound care products are costly. Hospitalization may be necessary for the treatment of cellulitis and ulcer débridement. Varicose veins increase the risk of DVT. Most skin changes present only a cosmetic problem.
Because of the chronicity of this disease, lifelong treatment is required. The mainstay of therapy is a sized-to-fit compression garment. Compression stockings are graded by the degree of compression applied to the legs. Although tighter compression stockings prevent more edema and ulceration, the choice of stocking should be determined by the patient's needs and limitations. Significant compression is contraindicated in patients with moderate to severe peripheral arterial disease. Some patients will not be able to comply with therapy because of osteoarthritis in the hands or limited flexibility. If possible, use of a lightweight garment (8-15 mm Hg compression) should be encouraged. Patients should be advised to use a good moisturizer, treat tinea pedis with an antifungal agent (a common source of cellulitis in patients with CVI), avoid prolonged standing or sitting, lose weight if appropriate, and exercise. A variety of surgical techniques are available for the treatment of secondary superficial varicosities.
The course of severe CVI is marked by periods of ulceration. The main concerns are sepsis that develops as a result of an infected ulcer or the occurrence of a DVT with thomboembolic complications.
ESSENTIALS OF DIAGNOSIS
Lymphedema is a pathological condition that develops when there is malformation, dysfunction, destruction, or obstruction of the lymphatic system. There are 2 forms of this disease: primary and secondary. Primary lymphedema can present at birth (Milroy's disease), develop during the second or third decade of life (lymphedema praecox), or manifest after the fourth decade (lymphedema tarda). Some forms are familial. Secondary lymphedema accounts for the majority of cases seen in the older population. Obstruction and inflammation are the usual inciting factors. Patients who have had cellulitis, lymphangitis, pelvic or leg radiation, trauma, surgery (including lymph node dissection), and cancer (either metastatic disease or a pelvic mass) are at greatest risk for lymphedema. Filariasis and other parasitic infections should be considered in any patient who has traveled or lived in endemic areas outside the United States.
Good foot and nail care is essential. Patients should be instructed to dry between their toes after bathing and use a topical antifungal agent if tinea pedis develops. Some individuals require chronic antibiotic therapy for recurrent cellulitis. Graduated compression stockings should be worn routinely.
Early in the course of development patients may not recognize lymphedema; however, most have impressive unilateral lower extremity swelling. The edema initially involves the toes and extends more proximally. Typically, the toes have a squared appearance (Stemmer's sign) and the dorsum of the foot is humped. With time, the skin thickens, developing deepened creases, hyperkeratosis, and papillomatosis, and the edema becomes resistant to pitting (“woody induration”). Although the edema is characteristically painless, patients complain of general leg discomfort, heaviness, and tightness as the limb enlarges. Signs of venous insufficiency are absent.
The diagnosis of lymphedema is suggested by history and physical examination in the absence of systemic disease. Lymphoscintigraphy is a confirmatory test that records radiolabeled tracer activity at specific time intervals, determines transit time through the lymphatics, and identifies the absence or presence and pattern of lymphatic channels and lymph node activity. Magnetic resonance imaging relies on the detection of a characteristic honeycomb pattern of edema within the epifascial plane and has the added benefit of allowing visualization of soft tissue in the limb. Computed tomography (CT) should be ordered if a pelvic malignancy is suspected.
Lymphedema can be difficult to distinguish from other causes of unilateral leg swelling. A venous duplex ultrasonogram is indicated if the swelling developed recently or rapidly to exclude DVT and popliteal (Baker's) cysts. Ecchymosis, especially around the ankle, is seen in patients who ruptured the medial head of the gastrocnemius muscle. Many of these patients report hearing a “pop” after stepping off a curb or walking down steps. Chronic regional pain syndrome (reflex sympathetic dystrophy) is associated with signs and symptoms of vasomotor instability, pain described as burning and aching, and a history of trauma to the limb.
Lymphedema is a disabling, chronic condition. Significant morbidity is due to a combination of the emotional, psychological, and physical aspects of this disease. Edema can limit mobility. Recurrent cellulitis and lymphangitis are common complications that can exacerbate swelling and require hospitalization for antibiotic therapy. Infrequently, patients with chronic lymphedema can develop a malignant lymphangiosarcoma heralded by the development of 1 or more flat, purple-blue skin lesions.
The focus of treatment is on reducing and then maintaining limb size, providing emotional support, and education of patients and caregivers. In general, diuretic therapy does not have a significant impact on decreasing the amount of protein-rich fluid in the subcutaneous tissue; therefore, it is of little benefit. Leg elevation allows passive drainage but does not stimulate the lymphatics. A variety of physical therapies are now available to reduce swelling. Mechanical devices delivering sequential pressure reduce limb volume by displacing the fluid. They should be used with caution in patients with volume-dependent diseases, including congestive heart failure, valvular disease, cirrhosis, and renal insufficiency. Manual lymphatic drainage, a massage technique, stimulates lymphatic flow and decongests the limb more gradually. It is often used in combination with multilayered bandaging and exercise. Graduated compression garments are required to maintain reduced limb size. The degree of compression is determined by severity of edema, presence of peripheral arterial disease, and anticipated rate of compliance. Compliance can be difficult to achieve. Patients may have difficulty putting on tight garments. The costs of garments can be prohibitive because Medicare does not cover them. Microvascular reconstruction and debulking or excisional procedures can be performed in select cases.
ESSENTIALS OF DIAGNOSIS
Venous thromboembolism (VTE) is a common disease with an annual incidence of approximately 1-2 per 1000 individuals. VTE has 2 clinical manifestations: DVT and pulmonary embolism (PE). The majority of symptomatic lower extremity DVT begins in the calf. Approximately 20–25% of calf vein DVT will extend into the proximal leg veins (popliteal, superficial and common femoral, iliac veins). Nearly 75% of all pulmonary emboli originate in the leg veins.
The risk of venous thromboembolism increases with advancing age independent of other factors. Several common thrombophilias have been identified, including factor V Leiden, prothrombin gene mutation 20210A, and hyperhomocysteinemia. However, hypercoagulable testing is rarely indicated in the geriatric population. These patients often have an identifiable risk factor. Myocardial infarction, stroke, congestive heart failure, nephrotic syndrome, varicose veins, inflammatory bowel disease, and obesity are independent risk factors for thrombosis. Immobility increases the risk of DVT. Likewise, hormone replacement therapy and selective estrogen receptor modulators for osteoporosis predispose women to VTE. Conditions associated with cancer treatment such as chemotherapy, surgery, radiotherapy, and central venous catheters increase VTE risk. Patients with a diagnosis of idiopathic DVT or PE should be evaluated for malignancy. The evaluation includes breast examinations, mammograms, pelvic examinations and Pap testing for women; a prostate exam and prostate-specific antigen testing for men; and a lower endoscopic examination for all individuals.
Surgery is another risk factor for VTE. The event rate after orthopedic surgery is especially high. More than 50% of patients undergoing hip and knee replacement surgery or surgery for a fractured hip will experience a DVT if prophylaxis is not given. The majority of these events involve the calf veins.
Prophylactic measures will reduce, but not eliminate, the risk of DVT and PE and should be administered to patients at high-risk for an event. Except for minor procedures, all patients older than 60 who have surgery are considered at high risk for VTE. Likewise, prophylaxis is indicated for immobilized and hospitalized patients, especially those who have had a myocardial infarction or an ischemic stroke resulting in impaired mobility.
The type and duration of prophylaxis is determined by the clinical indication for its use and the patient's comorbidities. The goal of nonpharmacological methods is to reduce venous stasis. Graded compression elastic stockings and intermittent pneumatic compression (IPC) are best reserved for patients with a contraindication to anticoagulation or as an adjunct to pharmacotherapy. A variety of anticoagulants are available, including adjusted-dose warfarin, unfractionated heparin, low-molecular-weight heparins, and pentasaccharide (Table 21-2). The choice of drug and dose varies according to the clinical indication.
An elevated D-dimer test is seen in most patients with venous thromboembolic disease but also in the setting of recent surgery, malignancy, trauma, and active cardiopulmonary disease. Therefore, the test is most useful
when performed in the outpatient setting in which these diagnoses are less likely to be present compared with the hospital setting. A normal D-dimer has a negative predictive value of 95% in patients suspected of having a DVT. The arterial blood gas can be normal or reveal a respiratory alkalosis resulting from hyperventilation in patients with PE. An elevated alveolar-arterial oxygen gradient may be detected.
Table 21-2. Dosing of anticoagulants for VTE prophylaxis and treatment.a
The gold standard study is contrast venography. The presence of an intraluminal filling defect or an abrupt cutoff is consistent with the diagnosis of a DVT. This test is more sensitive in detecting thrombosis in the calf veins, pelvic veins, and vena cava. However, it can be uncomfortable and is expensive. Occasionally, contrast-induced thrombosis occurs after venography. Venography should be used to confirm the diagnosis of DVT when the ultrasound is equivocal.
Ventilation-perfusion scanning, or lung scintigraphy, is performed by recording images of the lungs after intravenously injecting isotope-labeled macroaggregates of albumin and inhalation of a radioactive aerosol. Areas of “mismatch” where there is ventilation without perfusion are suggestive of a PE. The study is reported by assigning a probability of pulmonary embolism (normal, low, intermediate, or high). The diagnostic accuracy of the test improves when a pretest clinical probability is assigned. Lung scintigraphy is most helpful when interpreted as normal or high probability for PE. Otherwise, a confirmatory test may be required.
Spiral CT is more widely available than lung scintigraphy. It is inexpensive and has the advantage of detecting primary parenchymal disease. Pulmonary emboli appear as partial or complete intraluminal filling defects. Spiral CT is less sensitive in detecting peripheral emboli and must be performed with contrast; caution is necessary in patients with a decreased creatinine clearance.
Echocardiography remains an adjunctive test despite reports that it has been used to visualize thrombus. Its clinical utility in the management of PE is its ability to assess right ventricular (RV) function and estimate RV pressures. Almost half of all hemodynamically stable patients with a pulmonary embolism will have evidence of RV dysfunction. This finding is associated with an increase in mortality.
Pulmonary angiography remains the gold standard study for PE. The presence of an intraluminal filling defect or an abrupt cutoff is diagnostic. Similar to venography, it is expensive, invasive, requires contrast, and should only be used when a confirmatory test is required or an intervention is necessary.
Popliteal cysts and superficial thrombophlebitis can simulate a DVT with leg warmth, edema, and erythema. These diagnoses can usually be excluded using ultrasonography. A source for cellulitis is often identifiable. In general, lymphedema is painless and develops less rapidly. Chronic venous insufficiency, a potential complication of DVT, is associated with more chronic skin changes. Musculoskeletal sprains and injured muscles can be difficult to differentiate from a DVT. An acute arterial occlusion is painful and usually associated with loss of pedal pulses. Significant swelling tends to occur with limb reperfusion.
The signs and symptoms of a PE are nonspecific. They may be present with diseases involving the heart (congestive heart failure, pericarditis), lungs (asthma, pneumonia, pneumothorax), great vessels (aortic dissection), and muscles or bone (sprain, costochondritis).
Most patients who have had a DVT or PE will fully recover from the event. At least 30% of patients who have had a DVT will experience postthrombotic syndrome characterized by chronic pain and swelling in addition to other signs and symptoms of venous insufficiency. These symptoms can manifest in <2 years. A few patients will have chronic pulmonary thromboembolism with pulmonary hypertension after a PE. The implications of this complication in the older population are unclear.
The mainstay of treatment is anticoagulation (see Table 21-2). Age per se is not a contraindication to anticoagulation unless the patient is actively bleeding or has a high risk for complications (eg, inability to reliably take medications because of dementia or significant fall risk). Unfractionated heparin is administered using a weight-based dosing regimen with a target activated partial thromboplastin time (aPTT) of 1.5-2.5 times the mean control value. An aPTT should be drawn before drug initiation, 6 h after starting the drug or adjusting the dose, and once daily in a hospital setting.
Low-molecular-weight (LMW) heparins are easy to administer and can facilitate outpatient therapy or early discharge from the hospital. The drugs are administered subcutaneously and do not require monitoring. LMW heparin is cleared by the kidney and should be used cautiously in patients with renal insufficiency (they are contraindicated in patients with a creatinine clearance <30). The appropriateness of outpatient therapy must be judged for each individual patient, especially in the geriatric population. These drugs are costly and often not covered by insurance companies, including Medicare, for use on an outpatient basis.
Warfarin, the long-term anticoagulant of choice for most patients with venous thromboembolism, can be started on the same day as heparin by administering the anticipated daily dose requirement (eg, 5 mg). A 4- to 5-day overlap with heparin is necessary to ensure that all of the vitamin K-dependent factors have been adequately depleted. Patients with VTE or a known hypercoagulable state should not initially receive warfarin without simultaneous administration of another anticoagulant because of the risk of inducing a prothrombotic state by rapidly depleting protein C and S levels. The target international normalized ratio (INR) for most patients is 2.0-3.0 (higher in individuals with antiphospholipid antibody syndrome).
The optimal duration of therapy is not known. The decision regarding length of treatment depends on the patient's age, comorbidities, risk factors for VTE, and rate of recurrence. The duration of therapy for a patient with a reversible risk factor (eg, surgery, drugs) and a first VTE event is 3-6 mo. An idiopathic DVT or PE requires at least 6 mo of therapy. Patients with recurrent idiopathic events, some thrombophilias, and malignancy should receive long-term treatment.
Inferior vena cava (IVC) filters prevent embolization of thrombi from the legs to the lungs. However, these devices do not prevent recurrent DVT or extension of preexisting thrombus. In fact, the risk of recurrent DVT is increased long term. In addition, small thrombi can pass through the device struts or around the filter via collaterals. An IVC filter should be placed in patients with a contraindication to anticoagulation (eg, bleeding, surgery), recurrent VTE events despite an elevated INR,
and as an adjunct to surgical pulmonary embolectomy or thromboembolectomy. Perceived bleeding risk is important to consider in the geriatric population. For example, IVC filter placement may pose less of a risk to patients with a significant fall history.
Thrombolytic therapy is indicated in patients with a PE and hemodynamic instability. The benefits of this therapy must be weighed against the risks of bleeding. Approximately 15% of patients who are given thrombolytics will experience a significant bleed, most commonly gastrointestinal, genitourinary, or retroperitoneal. At least an additional 1–2% will have an intracranial bleed. Age over 70, recent stroke, surgery or gastrointestinal bleed, and uncontrolled hypertension are among the list of factors that increase bleeding risk. Geriatric patients with phlegmasia cerulea dolens should also be considered for thrombolytic therapy.
Venous thromboembolism is associated with significant morbidity and mortality. Many patients who die from PE are not diagnosed antemortem. The 3-mo mortality rate is increased by 60% in patients older than 70. Chronic thromboembolic pulmonary hypertension, a complication of pulmonary embolism, occurs infrequently. Up to 30% of patients with DVT will have postthrombotic syndrome. Sized-to-fit compression stockings decrease the risk of this complication.
Peripheral Arterial Disease
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Chronic Venous Insufficiency
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Hirsh J, Bates SM: Clinical trials that have influenced the treatment of venous thromboembolism: A historical perspective. Ann Intern Med 2001;134:409. [PMID: 11242501] (Good review of widely quoted studies that have influenced the standard of care for VTE treatment.)
Hyers TM et al: Antithrombotic therapy for venous thromboembolic disease. Chest 2001;119(suppl 1):176S. [PMID: 11157648] (American College of Chest Physicians guidelines from the sixth consensus conference on antithrombotic therapy.)
Kearon C et al: A comparison of 3 mo of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N Engl J Med 1999;340:901. [PMID: 10089183] (Trial terminated early after an increased risk of recurrent VTE was demonstrated in patients who had an idiopathic VTE and received only 3 mo of anticoagulation.)
Samama MM et al: A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in medical patients with enoxaparin study group. N Engl J Med 1999;341:793. [PMID: 10477777] (MEDENOX study compared placebo, enoxaparin 20 mg daily, and enoxaparin 40 mg daily for VTE prophylaxis.)
Turpie AG et al: Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: A meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162:1833. [PMID: 12196081] (Meta-analysis of the 4 large prospective trials using this new anticoagulant in orthopedic patients to prevent VTE.)
RELEVANT WORLD WIDE WEB SITES
HeartCenter Online: http://www.heartcenteronline.com/myheartdr/Articles_about_the_heart/The_Peripheral_Vascular_Center.html
Vascular Disease Foundation: http://www.vdf.org/PAD_Frame.htm
National Lymphedema Network: http://www.lymphnet.org
Circle of Hope Lymphedema Foundation, Inc.: http://www.lymphedemacircleofhope.org