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Pain and swelling of a leg is a relatively common presenting complaint in primary care practice. In the 1995 National Ambulatory Medical Care Survey, 1.3% of patients presenting to family physicians had a complaint of leg pain or swelling.1 Although this complaint often has a benign cause, it is important to carefully evaluate these patients because they may have deep vein thrombosis (DVT). A population-based study showed that 48 of 100,000 persons are given the diagnosis of DVT every year, which corresponds to 1 to 2 patients per year in a typical family physician’s panel of patients.2
Patients with a clotting abnormality who are pregnant, undergo a period of immobilization, or are diagnosed with a malignancy are at higher than average risk of DVT. In addition to the morbidity associated with DVT, approximately 40% of patients with DVT have a pulmonary embolism (PE), although most of these are clinically silent, and it is not clear whether aggressive work-up to diagnose PE in patients with DVT is indicated.3
This article describes an approach to the evaluation of patients with suspected DVT. The focus will be on making the best possible use of the history and physical examination by using our knowledge of the probability of DVT and validated clinical decision rules. This information will guide the interpretation of diagnostic tests such as d-dimer and duplex venous ultrasound.1
Differential diagnosis
There are many causes of leg pain and edema, including musculoskeletal injury, congestive heart failure, hepatic disease, mechanical obstruction of lymphatic drainage, cellulitis, malnutrition, thyroid disease, Baker cysts, chronic venous insufficiency, and venous thrombosis. Unfortunately, no detailed data are available for the percentage of patients given these diagnoses among all patients presenting with leg pain and swelling. Among all patients with leg pain with and without swelling only 3.3% had thrombophlebitis in a large Dutch series.4
A number of studies reporting data on the percentage of patients with suspected DVT who are referred for diagnostic testing and have the diagnosis confirmed are summarized in Table 1. As a rule of thumb, for every 100 outpatients with suspected DVT 16 will have a proximal DVT and 4 will have a distal DVT.
Using the history and physical examination
Individual signs and symptoms are of relatively little value in the diagnosis of DVT. The well-designed studies5,6 generally find a lower sensitivity or specificity for physical examination findings than poorly designed studies.7 The accuracy of individual history and examination findings are outlined in Table 2 using only data from the highest-quality study. Homan sign (long taught as a useful clinical sign) is of no value in the diagnosis of DVT and should be omitted from the examination.
However, groups of signs and symptoms can be useful. Wells and colleagues developed a clinical rule that combines the results of 9 carefully defined signs and symptoms Figure 1. They subsequently validated this rule in a later study using a different group of patients and found it useful for stratifying patients into separate groups by risk of having a DVT.8-10 This validation study included outpatients referred for the evaluation of suspected DVT to a tertiary care hospital thrombosis clinic. Patients were excluded if they were pregnant, had a lower extremity amputation, were suspected of having a PE, had symptoms for more than 60 days, or were currently using anticoagulants. The mean age was 57.1 years; 40% were men; and 16% were given a diagnosis of DVT. Thus, these data would generalize to a family practice setting. Patients who fell into the low-risk group based on this rule had a 3% risk of DVT; those in the moderate risk group, 17%; and those in the high-risk group, 75%. This information will determine how we interpret the results of the noninvasive tests.
Diagnostic tests
Tests for the diagnosis of DVT include impedance plethysmography, magnetic resonance imaging (MRI), duplex venous ultrasound, and contrast venography. The latter is an invasive test, typically considered the reference standard. The accuracy of noninvasive tests varies with the study population (symptomatic vs asymptomatic) and the type of DVT being diagnosed (proximal, distal, or any). The tests are generally much less accurate in asymptomatic patients and less accurate for distal DVTs. The data for impedance plethysmography and ultrasound are summarized in Table 3 for symptomatic patients.11-13 Although duplex venous ultrasound is clearly the preferred test, impedance plethysmography is an acceptable alternative if ultrasound is not available.
Although there is considerable interest in MRI, studies to date have been small14-16 or have had serious methodologic limitations, such as a failure to blind the radiologists, a retrospective design, or a poor quality reference standard.17-19 In these studies, the sensitivity ranges from 80% to 100% and the specificity from 93% to 100% when compared with contrast venography. Consideration of MRI should currently be limited to cases where venography is considered but there are concerns over the use of contrast, and where there is considerable local experience with the technique.20,21
Some physicians advocate repeating the duplex venous ultrasound in patients with an initial negative test result, if the suspicion for DVT remains. Two studies with a total of 2107 patients repeated the ultrasound 5 to 7 days later, if the first ultrasound result was normal; patients with 2 normal ultrasound results did not receive anticoagulation.22,23 Only 0.6% of these patients had a thromboembolic complication (DVT or pulmonary embolism) during the next 3 months, and only 1 of these occurred during the week between ultrasounds. A third study repeated the ultrasound 1 day and again 6 days later in patients with a normal initial ultrasound results.24 Of 390 patients with 3 normal ultrasound results, only 6 had a thromboembolic complication during the next 3 months. Thus, in patients with 2 normal results 1 week apart, the risk of a thromboembolic complication during the next 3 months is approximately 1%.
D-dimer is a fibrin degradation product, and elevated levels are associated with an increased risk of DVT. Different d-dimer assays vary considerably in their performance. Latex agglutination assays are fast and cheap but not very accurate; they are therefore not recommended. Microplate enzyme-linked immunoassays (ELISAs) are accurate but expensive; membrane ELISAs are less expensive and nearly as accurate. The accuracy of one of the most widely used d-dimer tests (SimpliRED) is shown in Table 3. Note that a negative d-dimer test rersult alone does not rule out DVT; 2% to 5% of patients with suspected DVT and a negative d-dimer result actually have DVT. This is similar to the performance of ultrasound alone in unselected patients with suspected DVT. Because of the differences between tests, clinicians should learn which test is used by their laboratory and should advocate for use of the most accurate available test.
The d-dimer test is most useful in a patient with a moderate risk of DVT and a normal duplex venous ultrasound result. In one study, only 1 of 598 patients with normal ultrasound and normal d-dimer test results (membrane ELISA; Instant-IA d-dimer kit, Stago, Asnieres, France) developed a DVT in the next 3 months. Of 88 patients with normal duplex venous ultrasound results but elevated d-dimer levels, 5 had a DVT detected 1 week later with a repeat ultrasound, and an additional 2 had venous thromboembolic complications during the next 3 months.25
Approaching the patient
Evaluating all patients with suspected DVT in the same way risks overdiagnosing low-risk patients and underdiagnosing high-risk patients. The history and physical examination can guide the selection and interpretation of further diagnostic tests. Begin by using the Wells clinical decision rule Figure 1 to put the patient in the low-, moderate-, or high-risk group. Remember that this rule was developed in nonpregnant patients with a first DVT. For pregnant patients or those with a history of previous DVT, you should have a higher index of suspicion.
Next, use the algorithm in Figure 2 to guide your evaluation. DVT can be considered adequately ruled out in low-risk patients with a negative ultrasound result and in moderate-risk patients with normal d-dimer and normal ultrasound results. Moderate-risk patients with a normal initial result on ultrasound but an abnormal d-dimer level should have a repeat ultrasound in 1 week. Moderate- and high-risk patients with an abnormal ultrasound result should be treated for DVT. High-risk patients with a normal ultrasound result still have a fairly high probability of DVT and should have a venogram to establish the diagnosis. In high-risk patients normal ultrasound and normal d-dimer results do not adequately rule out DVT.
Of course, this algorithm should not be used inflexibly. Patients with new or progressive symptoms (eg, a person with suspected DVT who develops signs and symptoms of PE) should be evaluated immediately. Pregnant patients and patients with a history of DVT should be evaluated more aggressively, because their overall risk of DVT is higher.
All correspondence should be addressed to Mark H. Ebell, MD, MS, 330 Snapfinger Drive, Athens, GA 30605. E-mail: ebell@msu.edu.
1. US Department of Health and Human Services. National Ambulatory Medical Care Survey (1995). NCHS CD-ROM Series 13, No. 11, SETS Version 1.221. Washington, DC: US Department of Health and Human Services; 1997.
2. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT study. Arch Intern Med 1991;151:933-38.
3. Meignan M, Rosso J, Gauthier H, et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med 2000;160:159-65.
4. Lamberts H. In Het Huis van de huisarts. Verslag van het Transitieproject. Lelystad: Meditekst, 2nd edition, 1994.
5. Sandler DA, Duncan JS, Ward P, et al. Diagnosis of deep-vein thrombosis: comparison of clinical evaluation, ultrasound, plethysmography, and venoscan with x-ray venogram. Lancet 1984;2:716-18.
6. O’Donnell TF, Jr, Abbott WM, Athanasoulis CA, Millan VG, Callow AD. Diagnosis of deep venous thrombosis in the outpatient by venography. Surg Gynecol Obstet 1980;150:69-74.
7. McLachlan J, Richards T, Paterson JC. An evaluation of clinical signs in the diagnosis of venous thrombosis. Arch Surg 1962;85:738-44.
8. Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995;345:1326-30.
9. Wells P, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-98.
10. Wells PS, Hirsch J, Anderson DR, et al. A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process. J Intern Med 1998;243:15-23.
11. Kearon C, Julian JA, Newman TE, Ginsberg JS. for the McMaster Diagnostic Imaging Practice Guidelines Initiative. Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med 1998;128:663-77.
12. Anderson DR, Wells PS, Stiell I, et al. Management of patients with suspected deep vein thrombosis in the Emergency Department: combining use of a clinical diagnosis model with d-dimer testing. J Emerg Med 2000;19:225-30.
13. Wildberger JE, Vorwerk D, Kilbinger M, et al. Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis: evaluation of 250 patients. Invest Radiol 1998;33:232-35.
14. Spritzer CE, Sostman HD, Wilkes DC, Coleman RE. Deep venous thrombosis: experience with gradient-echo MR imaging in 66 patients. Radiology 1990;177:235-41.
15. Moody AR, Pollock JG, O’Connor AR, Bagnall M. Lower-limb deep venous thrombosis: direct MR imaging of the thrombus. Radiology 1998;209:349-55.
16. Vukov LF, Berquist TH, King BF. Magnetic resonance imaging for calf deep venous thrombophlebitis. Ann Emerg Med 1991;20:497-99.
17. Laissy JP, Cinqualbre A, Loshkajian A, et al. Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography. Am J Roentgenol 1996;167:971-75.
18. Erdman WA, Jayson HT, Redman HC, et al. Deep venous thrombosis of extremities: role of MR imaging in the diagnosis. Radiology 1990;174:425-31.
19. Spritzer CE, Norconk JJ, Sostman HD, Coleman RE. Detection of deep venous thrombosis by magnetic resonance imaging. Chest 1993;104:54-60.
20. ACCP Consensus Committee on Pulmonary Embolism. Opinions regarding the diagnosis and management of venous thromboembolic disease chest. 1998;113:499-504.
21. American Thoracic Society. The diagnostic approach to acute venous thromboembolism clinical practice guideline. Am J Respir Crit Care Med 1999;160:1043-66.
22. Cogo A, Lensing AW, Koopman MW, et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ 1998;316:17-20.
23. Birdwell BG, Raskob GE, Whitsett TL, et al. The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis. Ann Intern Med 1998;128:1-7.
24. Heijboer H, Buller HR, Lensing AW, et al. A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med 1993;329:1365-69.
25. Bernardi F, Prandoni P, Lensing AWA, et al. D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ 1998;317:1037-40.
Pain and swelling of a leg is a relatively common presenting complaint in primary care practice. In the 1995 National Ambulatory Medical Care Survey, 1.3% of patients presenting to family physicians had a complaint of leg pain or swelling.1 Although this complaint often has a benign cause, it is important to carefully evaluate these patients because they may have deep vein thrombosis (DVT). A population-based study showed that 48 of 100,000 persons are given the diagnosis of DVT every year, which corresponds to 1 to 2 patients per year in a typical family physician’s panel of patients.2
Patients with a clotting abnormality who are pregnant, undergo a period of immobilization, or are diagnosed with a malignancy are at higher than average risk of DVT. In addition to the morbidity associated with DVT, approximately 40% of patients with DVT have a pulmonary embolism (PE), although most of these are clinically silent, and it is not clear whether aggressive work-up to diagnose PE in patients with DVT is indicated.3
This article describes an approach to the evaluation of patients with suspected DVT. The focus will be on making the best possible use of the history and physical examination by using our knowledge of the probability of DVT and validated clinical decision rules. This information will guide the interpretation of diagnostic tests such as d-dimer and duplex venous ultrasound.1
Differential diagnosis
There are many causes of leg pain and edema, including musculoskeletal injury, congestive heart failure, hepatic disease, mechanical obstruction of lymphatic drainage, cellulitis, malnutrition, thyroid disease, Baker cysts, chronic venous insufficiency, and venous thrombosis. Unfortunately, no detailed data are available for the percentage of patients given these diagnoses among all patients presenting with leg pain and swelling. Among all patients with leg pain with and without swelling only 3.3% had thrombophlebitis in a large Dutch series.4
A number of studies reporting data on the percentage of patients with suspected DVT who are referred for diagnostic testing and have the diagnosis confirmed are summarized in Table 1. As a rule of thumb, for every 100 outpatients with suspected DVT 16 will have a proximal DVT and 4 will have a distal DVT.
Using the history and physical examination
Individual signs and symptoms are of relatively little value in the diagnosis of DVT. The well-designed studies5,6 generally find a lower sensitivity or specificity for physical examination findings than poorly designed studies.7 The accuracy of individual history and examination findings are outlined in Table 2 using only data from the highest-quality study. Homan sign (long taught as a useful clinical sign) is of no value in the diagnosis of DVT and should be omitted from the examination.
However, groups of signs and symptoms can be useful. Wells and colleagues developed a clinical rule that combines the results of 9 carefully defined signs and symptoms Figure 1. They subsequently validated this rule in a later study using a different group of patients and found it useful for stratifying patients into separate groups by risk of having a DVT.8-10 This validation study included outpatients referred for the evaluation of suspected DVT to a tertiary care hospital thrombosis clinic. Patients were excluded if they were pregnant, had a lower extremity amputation, were suspected of having a PE, had symptoms for more than 60 days, or were currently using anticoagulants. The mean age was 57.1 years; 40% were men; and 16% were given a diagnosis of DVT. Thus, these data would generalize to a family practice setting. Patients who fell into the low-risk group based on this rule had a 3% risk of DVT; those in the moderate risk group, 17%; and those in the high-risk group, 75%. This information will determine how we interpret the results of the noninvasive tests.
Diagnostic tests
Tests for the diagnosis of DVT include impedance plethysmography, magnetic resonance imaging (MRI), duplex venous ultrasound, and contrast venography. The latter is an invasive test, typically considered the reference standard. The accuracy of noninvasive tests varies with the study population (symptomatic vs asymptomatic) and the type of DVT being diagnosed (proximal, distal, or any). The tests are generally much less accurate in asymptomatic patients and less accurate for distal DVTs. The data for impedance plethysmography and ultrasound are summarized in Table 3 for symptomatic patients.11-13 Although duplex venous ultrasound is clearly the preferred test, impedance plethysmography is an acceptable alternative if ultrasound is not available.
Although there is considerable interest in MRI, studies to date have been small14-16 or have had serious methodologic limitations, such as a failure to blind the radiologists, a retrospective design, or a poor quality reference standard.17-19 In these studies, the sensitivity ranges from 80% to 100% and the specificity from 93% to 100% when compared with contrast venography. Consideration of MRI should currently be limited to cases where venography is considered but there are concerns over the use of contrast, and where there is considerable local experience with the technique.20,21
Some physicians advocate repeating the duplex venous ultrasound in patients with an initial negative test result, if the suspicion for DVT remains. Two studies with a total of 2107 patients repeated the ultrasound 5 to 7 days later, if the first ultrasound result was normal; patients with 2 normal ultrasound results did not receive anticoagulation.22,23 Only 0.6% of these patients had a thromboembolic complication (DVT or pulmonary embolism) during the next 3 months, and only 1 of these occurred during the week between ultrasounds. A third study repeated the ultrasound 1 day and again 6 days later in patients with a normal initial ultrasound results.24 Of 390 patients with 3 normal ultrasound results, only 6 had a thromboembolic complication during the next 3 months. Thus, in patients with 2 normal results 1 week apart, the risk of a thromboembolic complication during the next 3 months is approximately 1%.
D-dimer is a fibrin degradation product, and elevated levels are associated with an increased risk of DVT. Different d-dimer assays vary considerably in their performance. Latex agglutination assays are fast and cheap but not very accurate; they are therefore not recommended. Microplate enzyme-linked immunoassays (ELISAs) are accurate but expensive; membrane ELISAs are less expensive and nearly as accurate. The accuracy of one of the most widely used d-dimer tests (SimpliRED) is shown in Table 3. Note that a negative d-dimer test rersult alone does not rule out DVT; 2% to 5% of patients with suspected DVT and a negative d-dimer result actually have DVT. This is similar to the performance of ultrasound alone in unselected patients with suspected DVT. Because of the differences between tests, clinicians should learn which test is used by their laboratory and should advocate for use of the most accurate available test.
The d-dimer test is most useful in a patient with a moderate risk of DVT and a normal duplex venous ultrasound result. In one study, only 1 of 598 patients with normal ultrasound and normal d-dimer test results (membrane ELISA; Instant-IA d-dimer kit, Stago, Asnieres, France) developed a DVT in the next 3 months. Of 88 patients with normal duplex venous ultrasound results but elevated d-dimer levels, 5 had a DVT detected 1 week later with a repeat ultrasound, and an additional 2 had venous thromboembolic complications during the next 3 months.25
Approaching the patient
Evaluating all patients with suspected DVT in the same way risks overdiagnosing low-risk patients and underdiagnosing high-risk patients. The history and physical examination can guide the selection and interpretation of further diagnostic tests. Begin by using the Wells clinical decision rule Figure 1 to put the patient in the low-, moderate-, or high-risk group. Remember that this rule was developed in nonpregnant patients with a first DVT. For pregnant patients or those with a history of previous DVT, you should have a higher index of suspicion.
Next, use the algorithm in Figure 2 to guide your evaluation. DVT can be considered adequately ruled out in low-risk patients with a negative ultrasound result and in moderate-risk patients with normal d-dimer and normal ultrasound results. Moderate-risk patients with a normal initial result on ultrasound but an abnormal d-dimer level should have a repeat ultrasound in 1 week. Moderate- and high-risk patients with an abnormal ultrasound result should be treated for DVT. High-risk patients with a normal ultrasound result still have a fairly high probability of DVT and should have a venogram to establish the diagnosis. In high-risk patients normal ultrasound and normal d-dimer results do not adequately rule out DVT.
Of course, this algorithm should not be used inflexibly. Patients with new or progressive symptoms (eg, a person with suspected DVT who develops signs and symptoms of PE) should be evaluated immediately. Pregnant patients and patients with a history of DVT should be evaluated more aggressively, because their overall risk of DVT is higher.
All correspondence should be addressed to Mark H. Ebell, MD, MS, 330 Snapfinger Drive, Athens, GA 30605. E-mail: ebell@msu.edu.
Pain and swelling of a leg is a relatively common presenting complaint in primary care practice. In the 1995 National Ambulatory Medical Care Survey, 1.3% of patients presenting to family physicians had a complaint of leg pain or swelling.1 Although this complaint often has a benign cause, it is important to carefully evaluate these patients because they may have deep vein thrombosis (DVT). A population-based study showed that 48 of 100,000 persons are given the diagnosis of DVT every year, which corresponds to 1 to 2 patients per year in a typical family physician’s panel of patients.2
Patients with a clotting abnormality who are pregnant, undergo a period of immobilization, or are diagnosed with a malignancy are at higher than average risk of DVT. In addition to the morbidity associated with DVT, approximately 40% of patients with DVT have a pulmonary embolism (PE), although most of these are clinically silent, and it is not clear whether aggressive work-up to diagnose PE in patients with DVT is indicated.3
This article describes an approach to the evaluation of patients with suspected DVT. The focus will be on making the best possible use of the history and physical examination by using our knowledge of the probability of DVT and validated clinical decision rules. This information will guide the interpretation of diagnostic tests such as d-dimer and duplex venous ultrasound.1
Differential diagnosis
There are many causes of leg pain and edema, including musculoskeletal injury, congestive heart failure, hepatic disease, mechanical obstruction of lymphatic drainage, cellulitis, malnutrition, thyroid disease, Baker cysts, chronic venous insufficiency, and venous thrombosis. Unfortunately, no detailed data are available for the percentage of patients given these diagnoses among all patients presenting with leg pain and swelling. Among all patients with leg pain with and without swelling only 3.3% had thrombophlebitis in a large Dutch series.4
A number of studies reporting data on the percentage of patients with suspected DVT who are referred for diagnostic testing and have the diagnosis confirmed are summarized in Table 1. As a rule of thumb, for every 100 outpatients with suspected DVT 16 will have a proximal DVT and 4 will have a distal DVT.
Using the history and physical examination
Individual signs and symptoms are of relatively little value in the diagnosis of DVT. The well-designed studies5,6 generally find a lower sensitivity or specificity for physical examination findings than poorly designed studies.7 The accuracy of individual history and examination findings are outlined in Table 2 using only data from the highest-quality study. Homan sign (long taught as a useful clinical sign) is of no value in the diagnosis of DVT and should be omitted from the examination.
However, groups of signs and symptoms can be useful. Wells and colleagues developed a clinical rule that combines the results of 9 carefully defined signs and symptoms Figure 1. They subsequently validated this rule in a later study using a different group of patients and found it useful for stratifying patients into separate groups by risk of having a DVT.8-10 This validation study included outpatients referred for the evaluation of suspected DVT to a tertiary care hospital thrombosis clinic. Patients were excluded if they were pregnant, had a lower extremity amputation, were suspected of having a PE, had symptoms for more than 60 days, or were currently using anticoagulants. The mean age was 57.1 years; 40% were men; and 16% were given a diagnosis of DVT. Thus, these data would generalize to a family practice setting. Patients who fell into the low-risk group based on this rule had a 3% risk of DVT; those in the moderate risk group, 17%; and those in the high-risk group, 75%. This information will determine how we interpret the results of the noninvasive tests.
Diagnostic tests
Tests for the diagnosis of DVT include impedance plethysmography, magnetic resonance imaging (MRI), duplex venous ultrasound, and contrast venography. The latter is an invasive test, typically considered the reference standard. The accuracy of noninvasive tests varies with the study population (symptomatic vs asymptomatic) and the type of DVT being diagnosed (proximal, distal, or any). The tests are generally much less accurate in asymptomatic patients and less accurate for distal DVTs. The data for impedance plethysmography and ultrasound are summarized in Table 3 for symptomatic patients.11-13 Although duplex venous ultrasound is clearly the preferred test, impedance plethysmography is an acceptable alternative if ultrasound is not available.
Although there is considerable interest in MRI, studies to date have been small14-16 or have had serious methodologic limitations, such as a failure to blind the radiologists, a retrospective design, or a poor quality reference standard.17-19 In these studies, the sensitivity ranges from 80% to 100% and the specificity from 93% to 100% when compared with contrast venography. Consideration of MRI should currently be limited to cases where venography is considered but there are concerns over the use of contrast, and where there is considerable local experience with the technique.20,21
Some physicians advocate repeating the duplex venous ultrasound in patients with an initial negative test result, if the suspicion for DVT remains. Two studies with a total of 2107 patients repeated the ultrasound 5 to 7 days later, if the first ultrasound result was normal; patients with 2 normal ultrasound results did not receive anticoagulation.22,23 Only 0.6% of these patients had a thromboembolic complication (DVT or pulmonary embolism) during the next 3 months, and only 1 of these occurred during the week between ultrasounds. A third study repeated the ultrasound 1 day and again 6 days later in patients with a normal initial ultrasound results.24 Of 390 patients with 3 normal ultrasound results, only 6 had a thromboembolic complication during the next 3 months. Thus, in patients with 2 normal results 1 week apart, the risk of a thromboembolic complication during the next 3 months is approximately 1%.
D-dimer is a fibrin degradation product, and elevated levels are associated with an increased risk of DVT. Different d-dimer assays vary considerably in their performance. Latex agglutination assays are fast and cheap but not very accurate; they are therefore not recommended. Microplate enzyme-linked immunoassays (ELISAs) are accurate but expensive; membrane ELISAs are less expensive and nearly as accurate. The accuracy of one of the most widely used d-dimer tests (SimpliRED) is shown in Table 3. Note that a negative d-dimer test rersult alone does not rule out DVT; 2% to 5% of patients with suspected DVT and a negative d-dimer result actually have DVT. This is similar to the performance of ultrasound alone in unselected patients with suspected DVT. Because of the differences between tests, clinicians should learn which test is used by their laboratory and should advocate for use of the most accurate available test.
The d-dimer test is most useful in a patient with a moderate risk of DVT and a normal duplex venous ultrasound result. In one study, only 1 of 598 patients with normal ultrasound and normal d-dimer test results (membrane ELISA; Instant-IA d-dimer kit, Stago, Asnieres, France) developed a DVT in the next 3 months. Of 88 patients with normal duplex venous ultrasound results but elevated d-dimer levels, 5 had a DVT detected 1 week later with a repeat ultrasound, and an additional 2 had venous thromboembolic complications during the next 3 months.25
Approaching the patient
Evaluating all patients with suspected DVT in the same way risks overdiagnosing low-risk patients and underdiagnosing high-risk patients. The history and physical examination can guide the selection and interpretation of further diagnostic tests. Begin by using the Wells clinical decision rule Figure 1 to put the patient in the low-, moderate-, or high-risk group. Remember that this rule was developed in nonpregnant patients with a first DVT. For pregnant patients or those with a history of previous DVT, you should have a higher index of suspicion.
Next, use the algorithm in Figure 2 to guide your evaluation. DVT can be considered adequately ruled out in low-risk patients with a negative ultrasound result and in moderate-risk patients with normal d-dimer and normal ultrasound results. Moderate-risk patients with a normal initial result on ultrasound but an abnormal d-dimer level should have a repeat ultrasound in 1 week. Moderate- and high-risk patients with an abnormal ultrasound result should be treated for DVT. High-risk patients with a normal ultrasound result still have a fairly high probability of DVT and should have a venogram to establish the diagnosis. In high-risk patients normal ultrasound and normal d-dimer results do not adequately rule out DVT.
Of course, this algorithm should not be used inflexibly. Patients with new or progressive symptoms (eg, a person with suspected DVT who develops signs and symptoms of PE) should be evaluated immediately. Pregnant patients and patients with a history of DVT should be evaluated more aggressively, because their overall risk of DVT is higher.
All correspondence should be addressed to Mark H. Ebell, MD, MS, 330 Snapfinger Drive, Athens, GA 30605. E-mail: ebell@msu.edu.
1. US Department of Health and Human Services. National Ambulatory Medical Care Survey (1995). NCHS CD-ROM Series 13, No. 11, SETS Version 1.221. Washington, DC: US Department of Health and Human Services; 1997.
2. Anderson FA, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism: the Worcester DVT study. Arch Intern Med 1991;151:933-38.
3. Meignan M, Rosso J, Gauthier H, et al. Systematic lung scans reveal a high frequency of silent pulmonary embolism in patients with proximal deep venous thrombosis. Arch Intern Med 2000;160:159-65.
4. Lamberts H. In Het Huis van de huisarts. Verslag van het Transitieproject. Lelystad: Meditekst, 2nd edition, 1994.
5. Sandler DA, Duncan JS, Ward P, et al. Diagnosis of deep-vein thrombosis: comparison of clinical evaluation, ultrasound, plethysmography, and venoscan with x-ray venogram. Lancet 1984;2:716-18.
6. O’Donnell TF, Jr, Abbott WM, Athanasoulis CA, Millan VG, Callow AD. Diagnosis of deep venous thrombosis in the outpatient by venography. Surg Gynecol Obstet 1980;150:69-74.
7. McLachlan J, Richards T, Paterson JC. An evaluation of clinical signs in the diagnosis of venous thrombosis. Arch Surg 1962;85:738-44.
8. Wells PS, Hirsh J, Anderson DR, et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995;345:1326-30.
9. Wells P, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-98.
10. Wells PS, Hirsch J, Anderson DR, et al. A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process. J Intern Med 1998;243:15-23.
11. Kearon C, Julian JA, Newman TE, Ginsberg JS. for the McMaster Diagnostic Imaging Practice Guidelines Initiative. Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med 1998;128:663-77.
12. Anderson DR, Wells PS, Stiell I, et al. Management of patients with suspected deep vein thrombosis in the Emergency Department: combining use of a clinical diagnosis model with d-dimer testing. J Emerg Med 2000;19:225-30.
13. Wildberger JE, Vorwerk D, Kilbinger M, et al. Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis: evaluation of 250 patients. Invest Radiol 1998;33:232-35.
14. Spritzer CE, Sostman HD, Wilkes DC, Coleman RE. Deep venous thrombosis: experience with gradient-echo MR imaging in 66 patients. Radiology 1990;177:235-41.
15. Moody AR, Pollock JG, O’Connor AR, Bagnall M. Lower-limb deep venous thrombosis: direct MR imaging of the thrombus. Radiology 1998;209:349-55.
16. Vukov LF, Berquist TH, King BF. Magnetic resonance imaging for calf deep venous thrombophlebitis. Ann Emerg Med 1991;20:497-99.
17. Laissy JP, Cinqualbre A, Loshkajian A, et al. Assessment of deep venous thrombosis in the lower limbs and pelvis: MR venography versus duplex Doppler sonography. Am J Roentgenol 1996;167:971-75.
18. Erdman WA, Jayson HT, Redman HC, et al. Deep venous thrombosis of extremities: role of MR imaging in the diagnosis. Radiology 1990;174:425-31.
19. Spritzer CE, Norconk JJ, Sostman HD, Coleman RE. Detection of deep venous thrombosis by magnetic resonance imaging. Chest 1993;104:54-60.
20. ACCP Consensus Committee on Pulmonary Embolism. Opinions regarding the diagnosis and management of venous thromboembolic disease chest. 1998;113:499-504.
21. American Thoracic Society. The diagnostic approach to acute venous thromboembolism clinical practice guideline. Am J Respir Crit Care Med 1999;160:1043-66.
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