The most common cause of leg swelling is edema, but all or part of a limb may expand due to an increase in any tissue component (muscle, fat, blood, etc). A correct diagnosis requires consideration of whether the swelling is acute or chronic, symmetric or asymmetric, localized or generalized, and congenital or acquired. Chronic swelling, particularly if asymmetric, is usually a sign of chronic edema arising from venous or lymphatic disease, whereas symmetric lower limb swelling suggests a systemic or more central cause of edema, such as heart failure or nephrotic syndrome. Edema develops when the rate of capillary filtration (lymph formation) exceeds lymphatic drainage, either because of increased capillary filtration, inadequate lymphatic flow, or both. Extracellular fluid volume is controlled principally by the lymphatic system, which normally compensates for increases in capillary filtration. Most edemas arise because filtration overwhelms the lymph drainage system. Increased capillary filtration may occur because of raised venous pressure, hypoalbuminemia, or increased capillary permeability due to local inflammation. The 2 main causes of a swollen lower limb are deep vein thrombosis and lymphedema (a failure of the lymph drainage system). In this article, we concentrate on deep vein thrombosis. Lymphedema is the focus of a subsequent article.
DEEP VEIN THROMBOSIS
Thrombosis usually develops as a result of venous stasis or slow-flowing blood around venous valve sinuses; extension of the primary thrombus occurs within or between the deep and superficial veins of the leg (figure 1), and the propagating clot causes venous obstruction), damage to valves, and possible thromboembolism. Deep vein thrombosis is often asymptomatic.
Figure 1.
Color duplex scan of deep vein thrombosis in common femoral vein adjacent to artery
Table 1.
| Causes of swelling of lower limb |
|---|
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ASSESSMENT AND INVESTIGATION
Various clinical features suggest deep vein thrombosis, but the findings of physical examination alone are notoriously unreliable (figure 2). Deep vein thrombosis is confirmed in only 1 of 3 cases suspected clinically. Confirmation of a suspected deep vein thrombosis requires the use of 1 or more investigations (figure 3), and the confirmation rate rises with the number of clinical risk factors. Identification of an underlying cause, if any, guides both the treatment and the approach to secondary prevention.,
Figure 2.
Right iliofemoral deep vein thrombosis
Figure 3.
Algorithm for investigation of deep vein thrombosis
Table 2.
| Clinical features of acute deep vein thrombosis |
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Table 3.
| Risk factors for deep vein thrombosis |
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The standard investigation is contrast venography (figure 4), but this invasive procedure is painful, often technically difficult and time-consuming, and occasionally complicated by thrombosis and extravasation of contrast. Recent developments in noninvasive testing mean that venography is now unnecessary in most patients, particularly those with suspected first proximal vein thrombosis.
Figure 4.
Venogram showing thrombus in lower leg
The accuracy of noninvasive techniques varies with the clinical circumstances. For example, compression ultrasonography and impedance plethysmography are accurate for detecting symptomatic proximal (iliofemoral) deep vein thrombosis, but both techniques are less satisfactory in asymptomatic patients and for detecting distal (calf vein) thrombosis. Compression ultrasonography has become the preferred first-line investigation.
Imaging techniques are generally less satisfactory in patients with suspected recurrent deep vein thrombosis, when confirmation of the diagnosis requires evidence of new thrombus formation—for example, the appearance of a new noncompressible venous segment on ultrasonography or a new intraluminal filling defect on venography.
Measurement of circulating D-dimer concentrations (a by-product of fibrin production) is a useful adjunct to ultrasonography, with 98% sensitivity for deep vein thrombosis and a high negative predictive value. The sensitivity of the test is lower for smaller calf vein thrombi. However, D-dimer concentrations rise as a nonspecific response to concomitant illness, not just thrombosis, so D-dimer test results can be misleading in patients admitted to a hospital for other reasons.
Table 4.
| Duration of anticoagulation in patients with deep vein thrombosis |
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A combination of diagnostic approaches—for example, compression ultrasonography coupled with clinical pretest probability scoring (table 1) or D-dimer measurements, or both, gives better diagnostic accuracy than any single investigation. Lensing and colleagues have recently shown that the combination of compression ultrasonography and D-dimer measurement is an efficient diagnostic approach, with a rate of subsequent thromboembolism of less than 1% in patients with false-negative results who were not treated with heparin. A robust investigational algorithm has been devised that does not include the routine use of venography (see figure 3).
Table 1.
Clinical model to measure pretest probability of deep vein thrombosis*
| Clinical features | Score |
|---|---|
| Active cancer (treatment ongoing, or within 6 months, or palliative) | 1 |
| Paralysis, paresis, or recent plaster immobilization of the legs | 1 |
| Recent immobilization >3 days or major surgery within 12 weeks requiring general or regional anesthesia | 1 |
| Localized tenderness along the distribution of the deep venous system | 1 |
| Entire leg swollen | 1 |
| Calf swollen 3 cm more than asymptomatic side (measured 10 cm below tibial tuberosity) | 1 |
| Pitting edema confined to the symptomatic leg | 1 |
| Collateral superficial veins (nonvaricose) | 1 |
| Alternative diagnosis equally or more likely than deep vein thrombosis | -2 |
A score of 3 indicates high risk; 1 or 2, moderate risk; and o, low risk.
Complications
The main complications of deep vein thrombosis are pulmonary embolism, postthrombotic syndrome, and recurrence of thrombosis. Proximal thrombi are a major source of morbidity and mortality. Distal thrombi are generally smaller and more difficult to detect noninvasively, and their prognosis and clinical importance are less clear. However, a fifth of untreated newly developing calf vein thrombi extend proximally, and a quarter are associated with long-term symptoms of post-thrombotic syndrome; treating proven significant calf vein thrombosis is, therefore, appropriate.
Postthrombotic syndrome develops as a result of high venous pressure due to thrombotic damage to valves. It complicates 50% to 75% of deep vein thromboses, and a strong association exists with ipsilateral recurrence. Clinical features include pain, swelling, dermatitis, and ulceration. Proximal deep vein thrombosis is associated with a higher frequency and greater severity of postthrombotic syndrome, but the risk is halved by the use of graded compression stockings after deep vein thrombosis.
Prevention
Patients at significantly increased risk of deep vein thrombosis—for example, those having major pelvic or abdominal surgery for cancer or those with a history of pulmonary embolism or deep vein thrombosis who have serious trauma or illness or who are having major surgery (table 2)—should be given prophylaxis. Early mobilization and graded compression stockings are effective, and antiplatelet drugs such as aspirin provide additional protection.,
Table 2.
Absolute risks of venous thrombotic complications in procedures or conditions of low, moderate, and high risk
| Risk level | Deep vein thrombosis | Risk, % Proximal deep vein thrombosis | Fatal pulmonary embolism | Examples |
|---|---|---|---|---|
| Low | <10 | <1 | 0.01 | Minor surgery, trauma, or medical illness |
| Major surgery at age <40 yr with no other risk factors | ||||
| Moderate | 10-40 | 1-10 | 0.01-1.0 | Major surgery with another risk factor |
| Major trauma, medical illness, or burns | ||||
| Emergency cesarean section in labor | ||||
| Minor surgery with previous deep vein thrombosis, pulmonary embolism, or thrombophilia | ||||
| Lower limb paralysis | ||||
| High | 40-80 | 10-30 | 1-10 | Major pelvic or abdominal surgery for cancer |
| Major surgery, trauma, or illness with previous pulmonary embolism, deep vein thrombosis, or thrombophilia |
Table 6.
| Indications for insertion of an inferior vena cava filter |
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| Controversial indications |
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Table 8.
| Deep vein thrombosis in pregnancy and puerperium and in women taking contraceptive pill or hormone replacement therapy |
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Pneumatic compression devices (figure 5) have been proved effective when used perioperatively and in some groups of medical patients. Low-dose unfractionated heparin (5,000 units 2 hours before surgery and every 8-12 hours postoperatively) given subcutaneously reduces the rate of postoperative thromboembolism in patients having general surgery by 65%, with little increase in the risk of serious bleeding. Low-molecular-weight (LMW) heparins are effective and have some advantages over unfractionated heparin, particularly in high-risk patients such as those having hip replacement.
Figure 5.
Pneumatic compression devices
Treatment
Treatment is aimed at reducing symptoms and preventing complications. Elevation of the leg with some flexion at the knee helps reduce swelling, early mobilization is beneficial, and the use of graded compression stockings achieves a 60% reduction in the incidence of postthrombotic syndrome.
It is important to establish effective anticoagulation rapidly. Patients are usually given an initial intravenous bolus of heparin of 5,000 units, followed by unfractionated or LMW heparin for at least 5 days. With unfractionated heparin, an intravenous constant infusion and subcutaneous injection twice a day are equally effective. A heparin algorithm should be used to adjust the dose. The activated partial thromboplastin time should be checked every 6 hours until the target is reached and then daily to maintain the international normalized ratio at 1.5 to 2.5. The platelet count should be checked at the start of treatment and on day 5 to exclude thrombocytopenia. A warfarin sodium regimen should be started on day 1, with the dose determined by a warfarin algorithm. The target ratio is 2 to 3, and heparin can be stopped when the target ratio is maintained for more than 24 hours.
Patients with deep vein thrombosis who do not need to be in a hospital (around 35%) can be treated with subcutaneous LMW heparin in the community. This can be administered subcutaneously once or twice a day. LMW heparin has the advantages of a slightly lower rate of hemorrhage and thrombocytopenia and more reliable absorption after injection, and anticoagulation monitoring is not required routinely. The warfarin regimen should be started on day 1 and the duration of treatment guided by the risk profile.
Other approaches
Inferior vena cava filters reduce the rate of pulmonary embolism (figure 6) but have no effect on the other complications of deep vein thrombosis. Thrombolysis should be considered in patients with major proximal vein thrombosis and threatened venous infarction. Surgical embolectomy is restricted to patients with life-threatening proximal thrombosis and when all else has failed.
Figure 6.
Vena cavagram showing umbrella delivery device inserted into the inferior vena cava through the jugular vein. The filter has been released just below the renal veins. Inferior vena cava filters help prevent pulmonary embolism but not other complications of deep vein thrombosis, including recurrent thrombosis.
Pregnancy
Anticoagulating doses of heparin are given for deep vein thrombosis in pregnancy. It is essential to confirm the presence of a thrombus objectively. This is usually done by compression ultrasonography (serially if necessary).
A regimen of unfractionated heparin or LMW heparin (which has a better risk profile) should then be continued throughout the pregnancy and stopped temporarily before delivery. Anticoagulation therapy should be restarted in the puerperium and continued for 6 weeks to 3 months. Warfarin is usually contraindicated during pregnancy because it is teratogenic and increases the risk of maternal and fetal hemorrhage perinatally. It can be restarted 48 hours after delivery.
Further reading and useful references
Levick JR. An Introduction to Cardiovascular Physiology. 2nd ed. Oxford: Butterworth-Heinemann; 1995.
Lensing AW, Prandoni P, Prins MH, Buller HR. Deep-vein thrombosis. Lancet 1999;353:479-485.
Second Thromboembolic Risk Factors (THRiFT II) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. Phlebology 1998;13:87-97.
Kearon C, Julian JA, Newman TE, Ginsberg JS. Noninvasive diagnosis of deep venous thrombosis: McMaster Diagnostic Imaging Practice Guidelines Initiative. Ann Intern Med 1998;128:663-677 [published erratum appears in Ann Intern Med 1998;129:425].
Anderson DR, Wells PS. Improvements in the diagnostic approach for patients with suspected deep vein thrombosis or pulmonary embolism. Thromb Haemost 1999;82:878-886.
Prins MH, Hutten BA, Koopman MMW, Buller HR. Long-term treatment of venous thromboembolic disease. Thromb Haemost 1999;82:892-898.
Competing interests: None declared This article was published in BMJ 2000;320:1453-1456 as part of the series, “ABC of arterial and venous disease”
Authors: Peter Gorman is consultant physician and Karl Davis is clinical research fellow, Southern Derbyshire Acute Hospitals National Health Service Trust, Derby. The ABC of arterial and venous disease is edited by Richard Donnelly, professor of vascular medicine, University of Nottingham and Southern Derbyshire Acute Hospitals National Health Service Trust (richard.donnelly@nottingham.ac.uk) and Nick J M London, professor of surgery, University of Leicester, Leicester (sms 16@leicester.ac.uk). It will be published as a book later this year.