- Email: [email protected]
Diagnosis of deep venous thrombosis
clinical CORNERSTONE
.
DEEPVENOUSTHROMBOSIS
* Vol.2 No.4
Diagnosis of Deep Venous Thrombosis Samuel
Z. Goldhaber,
MD
Staff Cardiologist Cardiovascular Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, Massachusetts ph: 6 17-732-7566 e-mail: [email protected]
Although deep venous thrombosis (DVT) zs * oft en considered an elusive disease that is dzJ%ult to recognize clinically, important clinical clues and properly ordered imaging tests can reliably detect or exclude this condition. This article will provide a practical approach to recognizing clinical settings in which DVT should be suspected, suggesting a focused history and physical examination and outlining optimal strategies for test ordering. This information will help ensure that patients with DVTare identified rapidly and, conversely, that those without DVT will receive reassurance or spec;fc treatment for the medicalproblem that mimics it. Once DVT can proceed rapidly and accurately to resolve the didgnostic issue.
Deep venous thrombosis (DVT).can manifest with a wide range of venous involvement. Perhaps most benign is the DVT that affects only an isolated calf vein. At the medically severe end of the spectrum is massive DVT, usually lodged in the inferior vena cava or iliofemoral venous system, that can dislodge, embolize, and cause fatal pulmonary embolism (PE). One must also keep in mind the frequently overlooked upper-extremity venous thrombi. As with isolated calf DVT, these used to be dismissed as medically inconsequential. We now know, however, that blood clots in these upper-extremity and isolated calf DVT vascular beds are serious and require urgent, acute management. In as many as 25% of patients, these clots can cause PE (usually asymptomatic). A full discussion of venous thrombosis necessitates mention of portal vein, superior mesenteric, and cerebral vein thromboses. These latter 3 conditions, however, will not be discussed in this article.
is suspected, a workup
CLINICAL SETTING DVT may range in severity from a nuisance problem with a mild impact on quality of life to a life-threatening condition resulting in venous gangrene or massive PE. In tertiary-care hospitals, DVT patients who have protracted inpatient stays are often ill because of concomitant cancer or surgery. Bleeding or failure of anticoagulation requiring placement of a vena caval filter may complicate their clinical
29
clinical CORNERSTONE
.
DEEPVENOUSTHROMBOSIS
1 Vol.2 No.4
and chills usually suggest cellulitis rather than DVT, although DVT may be present concomitantly. Nevertheless, clinicopathologic conferences often try to trick invited discussants by selecting cases of DVT that present as fever of unknown origin. Do not assume that patients receiving prophylactic heparin are always protected from DVT. In fact, such patients are susceptible to massive DVT, often bilateral, if heparin-induced thrombocytopenia develops during heparin administration. (Heparin-induced thrombocytopenia is more likely to occur if unfractionated heparin is used rather than low-molecular-weight heparin.) It is ironic that heparin-induced thrombocytopenia is associated with clotting rather than bleeding. In fact, if bleeding occurs in the presence of thrombocytopenia, the cause of the low platelet count is probably not related to heparin use.
course. In this ill population, the mortality rate at 3 months may approach 20%. DVT may first be suspected simply by an ominous clinical setting such as recent trauma, surgery, or immobilization from a long airplane flight. Contributing risks include a past history or family history of DVT as well as a previously diagnosed hypercoagulable state such as factor V Leiden, hyperhomocystinemia, or anticardiolipin antibodies. Marked obesity and cigarette smoking also increase the risk of DVT. Upper-extremity venous thrombosis, in particular, is associated with indwelling central venous catheters, hypercoagulable states, and a history of DVT of the leg. From a women’s health perspective, pregnancy, oral contraceptives, and hormone replacement
Physical Examination When DVT is detected early after onset, the physical findings may be minimal, consisting of mild palpation discomfort in the lower calf. At the other end of the spectrum is massive thigh swelling and marked tenderness when palpating the inguinal area over the course of the femoral vein. Such patients often have difficulty walking and may require a cane, crutches, or walker. Erythema usually suggests concomitant superficial venous phlebitis with saphenous vein involvement or coexisting cellulitis. If a patient has upper-extremity venous thrombosis, there may be asymmetry in the supraclavicular fossae or in the girth of the upper arms. Also, look for a prominent superficial venous pattern over the anterior chest wall. A respiratory rate (count it yourself) that exceeds 16 respirations per minute, coupled with labored breathing, should suggest that a portion of the suspected DVT has already embolized to the lungs. If the workup for DVT proves negative, an investigation for PE should be undertaken. If the leg is diffusely edematous, DVT is an unlikely diagnosis. Much more common is an acute exacerbation of venous insufficiency due to postphlebitic syndrome. Under extreme and rare circumstances venous ulceration can occur. The
will double or triple the risk of DVT. Fortunately, the absolute incremental risk is low (no more than 1 additional DVT per 1000 woman-years). It is important to recognize that as many as half of the patients with DVT may have no symptoms or signs. Therefore, maintaining a high level of clinical suspicion is of paramount importance.
History Discomfort that was at first intermittent becomes persistent; swelling may ensue. The patient who seeks medical attention may know someone who has suffered DVT but may be reluctant to state that DVT is feared. The most common story told by patients with DVT is of a cramp or charley horse in the lower calf that does not abate after several days; in fact, it gradually worsens. Certain features of a history argue against DVT. The discomfort from DVT rarely has an abrupt onset. Sudden, excruciating calf discomfort is most likely due to a ruptured Baker’s cyst. Fever
30
clinical CORNERSTONE
= DEEPVENOUSTHROMBOSIS
* Vol.2 No.4
Active cancer (treatment ongoing, or within previous 6 months, or palliative) Paralysis, paresis, or recent plaster immobilization
of the lower extremities
Recently bedridden for >3 days or major surgery within 4 weeks Localized
tenderness along the distribution
of the deep venous system
Entire leg swollen Calf swelling by >3 cm when compared with the asymptomatic
leg (measured
10 cm below tibia1 tuberosity) Pitting edema (greater in the symptomatic Collateral Alternative
superficial
1 leg)
1
veins (nonvaricose)
1
diagnosis as likely as or greater than that of deep vein thrombosis
-2
*Note: In patients with symptoms in both legs, the more symptomatic leg should be used. High pretest probability = 23 points; moderate pretest probability = l-2 points; low pretest probability = zero or negative points. Reprinted with permission from Wells PS, Anderson D, Bormanis J, et al. Value of assessment of pretest probability vein thrombosis in clinical management. Luncet. 1997;350:1796.
distinction between venous insufficiency and acute DVT is crucial. The former condition is managed with vascular compression stockings alone; the latter problem requires immediate administration of anticoagulants.
of deep-
Doppler imaging, is known as duplex sonography and is the principal diagnostic imaging test for suspected acute DVT. Sonographic evaluation utilizes compression ultrasound along the full length of the femoral, popliteal, and calf veins. The transducer is held transverse to the vein, and normally, the vein collapses with gentle manual compression. The compressed vein appears as if it is winking. The main criterion for diagnosing DVT is lack of compression of a deep vein. This diagnosis can be confirmed by direct visualization of thrombus on ultrasound or by abnormal venous flow on Doppler examination (eg, loss of physiologic respiratory variation or loss of the expected augmentation of blood flow during calf compression). Among symptomatic patients, duplex sonography is very accurate, with high sensitivity and specificity (Figure 1). Its sensitivity decreases when assessing patients with isolated calf DVT or asymptomatic patients. Major limitations include inability in most situations to directly image pelvic vein thrombosis and difficulty diagnosing acute superimposed on chronic DVT. I do not advocate a strategy of serial ultrasonographic testing when results are equivocal. In these circumstances I
Clinical Modeling of Pretest Probability A Canadian group developed and tested a clinical model to predict the pretest probability for DVT. It relies on a scoring system with 9 parameters that can be quickly assessed based on the clinical setting, history, and physical examination (Table). Four of 9 parameters focus on clinical setting and history, while the other 5 depend on the physical examination of the legs. Results are then tabulated into 3 categories depending on the final score: high, moderate, and low pretest probability for DVT. I believe this modeling is useful as a reminder of the components of DVT workup other than imaging tests. However, I do not personally use this scoring system in my daily practice.
IMAGING TESTS Venous Ultrasonography Venous ultrasonography, combined with color
31
clinical CORNERSTONE
.
QEEPVENOUSTHROMBOSIS
q
Vol.2 No.4
The principal problem with this approach is low sensitivity of IPG, even for massive nonobstructing DVT, and a high false-negative rate. I believe that IPG should no longer be used for routine evaluation of patients with suspected acute DVT.
Contrast Venography Although contrast venography has traditionally been considered the gold standard for DVT diagnosis, many specialists now believe that duplex sonography and MRI are more accurate. Contrast venography does not yield a definitive diagnosis when there is total obstruction of the deep venous system because the contrast agent cannot gain access to the occluded segment. Furthermore, I can personally attest to the difficulty in interpreting the results of calf venography because there are myriad tiny and overlapping veins to analyze. Despite its limitations, a properly performed contrast venogram is beautiful to behold (Figure 2). It can show clearly a meniscus of fresh thrombus. It can define the extent and precise anatomical location of the DVT. The venogram can also demonstrate the presence of collaterals and can provide firm indications of whether the patient has suffered previous venous disease. Finally, the venogram
Figure 1. Venous ultrasound with color Doppler imaging of the proximal right leg veins at the junction of the superficial femoral vein (SFV), which despite its name, is a deep leg vein, and the profunda (deep) femoral vein (PFV) as they merge into the common femoral (CF) vein. In the original venogram, color flow is normal (red) in the femoral artery and normal (blue) in the PFV There is no thrombus in the PFR However, the SFV contains a totally obstructing thrombus (arrowheads).
prefer to select an alternative diagnostic modality such as magnetic resonance imaging (MRI) or contrast venography.
Impedance Plethysmography This diagnostic method assesses electrical conductivity by measuring the resistance (impedance) to a weak current passed through the leg. This weak current is imperceptible to the patient and is incapable of stimulating the heart. Normally, conductivity increases (as the impedance decreases) while blood accumulates during inflation of an impedance plethysmography (IPG) cuff around the calf. Conversely, conductivity decreases (as the impedance increases) when blood drains from the calf during IPG cuff deflation. These electrical changes are reduced in patients with DVT.
can demonstrate abnormal connections between the superficial and deep venous systems typical of patients with venous insufficiency. Contrast venography is an uncomfortable, invasive test. It causes a chemical phlebitis in about 1% of patients. One must always keep in
32
cUnical CORNERSTONE
m DEEPVENOUSTHROMBOSIS
= Vol.2 No.4
Figure 3. Magnetic resonance image of a normal popliteal vein, demonstrating the extraordinary resolution and detail that can be obtained with this imaging method. Reprinted with permission from Wolfe MU: Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment Curr Probl Cardiol. with thrombolytic therapy. 1993; 10:585-636.
Figure 2. Contrast venogram of the leg. Contrast tracks between the large popliteal vein thrombus and the vessel wall, creating the “tram-track” sign of an acute DVT. The proximal aspect of the thrombus is convex. Reprinted with permission from Wolfe MW Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment Curr Probl Cardiol. with thrombolytic therapy. 1993;10:585-636.
Contrast venography, ironically, is undergoing a renaissance as interventional angiographers select patients with massive iliofemoral DVT or recurrent DVT who require laboratory procedures such as catheter-directed thrombolysis, suction or rotational catheter thrombectomy, venous angioplasty, or venous stenting. When these procedures are required, contrast venography is a necessity.
mind the possibility of allergy to the contrast agent and to worsening renal function in patients with baseline renal insufficiency. For these latter patients, ask your angiographer to consider using carbon dioxide gas rather than standard contrast as the imaging agent. Furthermore, a “Catch-22” situation has evolved in which trainees receive very little experience in performing and interpreting contrast venography. Therefore, when a high-quality contrast venogram is required, skilled operators are difficult to find for this diagnostic study, and it has become a lost art.
Magnetic Resonance Imaging Use of MRI depends on the resources, interest level, and skill of the radiologists at your hospital. When properly performed, this noninvasive test can provide surprisingly precise, detailed information about the venous system (Figure 3). MRI can also help estimate the age of a thrombus based on various “spin” characteristics of the image. I find MRI especially useful in assessing suspected pelvic vein
33
dinid
CORNERSTONE
n
DEEPVENOUSTHROMBOSIS
n
Vol. 2 No. 4
Figure 4. Diagnostic algorithm for DVT A4RI = magnetic resonance imaging.
thrombosis and in defining the extent of upperextremity vein thrombosis.
Nuclear Venography In 1998, the US Food and Drug Administration approved technetium-99m-apcitide for the diagnosis of acute leg DVT. A complex of the synthetic peptide (apcitide) and the radionuclide (technetium) binds preferentially to the glycoprotein IIb/IIIa receptors found on activated platelets. This diagnostic method may be complementary to ultrasonography and provide information on pelvic vein thrombosis (not ordinarily imaged by ultrasound), acute superimposed upon chronic DVT (poorly differentiated by ultrasound), and acute DVT when the ultrasound examination is technically limited due to body habitus or ambiguous findings. Broad clinical experience with this technique is not yet available, however.
OVERALL DIAGNOSTIC ALGORITHM FOR DVT The first step in a diagnostic algorithm (Figure 4) for DVT is suspecting this disease entity based on the clinical setting, symptoms, and signs elicited from evaluation of the patient. The initial imaging test should be venous ultrasonography, with color Doppler imaging if available. If positive, treatment
34
clinical CORNERSTONE
.
DEEPVENOUSTHROMBOSIS
- Vol.2 No.4
Cogo A, Lensing AWA, Koopman MMW, et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;3 16: 17-20. Cornuz J, Pearson SD, Polak JF. Deep venous thrombosis: complete lower extremity venous US evaluation in patients with known risk factors-outcome study. Radiology. 1999;211:637-641.
for DVT should commence. In most instances, therapy will consist of anticoagulation alone. Under some circumstances, however, a more interventional approach will be required with mechanical intervention or catheter-directed thrombolysis. To perform these procedures, contrast venography will be necessary. If duplex sonography is negative, the workup for DVT can usually be discontinued. The only caveat is to continue the investigation for DVT in the presence of very high clinical suspicion despite a negative ultrasound examination. Such patients
de Moerloose P, Michiels JJ, Bounameaux H. The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism. Semin Thromb Hemost. 1998;24:409412. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 1998;114:5618-5788.
would have classic historical features and physical examination findings for DVT. The workup should also continue if the ultrasound results are equivocal. This is often the case in patients with marked obesity, leg edema, or pain upon leg palpation in whom a technically adequate study simply cannot be obtained. Under these circumstances, further imaging should
Ibrahim S, MacPherson DR, Goldhaber SZ. Chronic venous insufficiency: mechanisms and management. Am Heart J. 1996;132:856860.
proceed either with contrast venography or MRI.
Kahn SR. The clinical diagnosis of deep venous thrombosis. Integrating incidence, risk factors, and symptoms and signs. Arch Intern Med. 1998;158:2315-2323.
Jongbloets LMM, Lensing AWA, Koopman MMW, et al. Limitations of compression ultrasound for the detection of symptomless postoperative deep vein thrombosis. Lancet. 1994;343:1142-1144.
SUMMARY
This imaging test is widely available and
Kearon C, Ginsberg JA, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med. 1998;129:1044-1049.
can generally be performed with high-quality results. It facilitates and simplifies the management of patients who may be afflicted with this morbid and potentially fatal disease.
Piccioli A, Prandoni P, Goldhaber SZ. Epidemiologic characteristics, management, and outcome of deep venous thrombosis in a tertiary-care hospital: The Brigham and Women’s Hospital DVT Registry. Am Heart J. 1996;132:1010-1014.
SUGGESTED
Prandoni P, Polistena P, Bernardi E, et al. Upperextremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med. 1997;157:57-62.
High-resolution
venous ultrasonography
has revo-
lutionized the diagnostic algorithm for acute DVT.
READING
Anand SS,Wells PS, Hunt D, et al. Does this patient have deep vein thrombosis? JAMA. 1998;279:1094-1099.
Simons GR, Skibo LK, Polak JF, et al. Utility of leg ultrasonography in suspected symptomatic isolated calf deep venous thrombosis. Am J Med. 1995;99:43-47.
Anderson DR, Wells PS. Improvements in the diagnostic approach for patients with suspected deep vein thrombosis or pulmonary embolism. Thromb Huemost. 1999;82:878-886.
Warkentin TE. Heparin-induced thrombocytopenia: a ten-year retrospective. Annu Rev Med. 1999;50:129-147. Wells PS, Anderson D, Bormanis J, et al. Value of assessmentof pretest probability of deep-vein thrombosis in clinical management. Luncet. 1997;350:1795-1798.
Birdwell BG, Raskob GE, Whitsett TL, et al. The clinical validity of normal compression ultrasonography in . outpatients suspected of having deep vein thrombosis. Ann Intern Med. 1998;128:1-7.
Wolfe MW, Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment with thrombolytic therapy. Curr Probl Cardiol. 1993;10:585%636.
Bundens WP, Bergan JJ, Halasz NA, et al. The superficial femoral vein. A potentially lethal misnomer. JAMA. 199.5;274:1296-1298.
35
.
DEEPVENOUSTHROMBOSIS
* Vol.2 No.4
Diagnosis of Deep Venous Thrombosis Samuel
Z. Goldhaber,
MD
Staff Cardiologist Cardiovascular Division Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, Massachusetts ph: 6 17-732-7566 e-mail: [email protected]
Although deep venous thrombosis (DVT) zs * oft en considered an elusive disease that is dzJ%ult to recognize clinically, important clinical clues and properly ordered imaging tests can reliably detect or exclude this condition. This article will provide a practical approach to recognizing clinical settings in which DVT should be suspected, suggesting a focused history and physical examination and outlining optimal strategies for test ordering. This information will help ensure that patients with DVTare identified rapidly and, conversely, that those without DVT will receive reassurance or spec;fc treatment for the medicalproblem that mimics it. Once DVT can proceed rapidly and accurately to resolve the didgnostic issue.
Deep venous thrombosis (DVT).can manifest with a wide range of venous involvement. Perhaps most benign is the DVT that affects only an isolated calf vein. At the medically severe end of the spectrum is massive DVT, usually lodged in the inferior vena cava or iliofemoral venous system, that can dislodge, embolize, and cause fatal pulmonary embolism (PE). One must also keep in mind the frequently overlooked upper-extremity venous thrombi. As with isolated calf DVT, these used to be dismissed as medically inconsequential. We now know, however, that blood clots in these upper-extremity and isolated calf DVT vascular beds are serious and require urgent, acute management. In as many as 25% of patients, these clots can cause PE (usually asymptomatic). A full discussion of venous thrombosis necessitates mention of portal vein, superior mesenteric, and cerebral vein thromboses. These latter 3 conditions, however, will not be discussed in this article.
is suspected, a workup
CLINICAL SETTING DVT may range in severity from a nuisance problem with a mild impact on quality of life to a life-threatening condition resulting in venous gangrene or massive PE. In tertiary-care hospitals, DVT patients who have protracted inpatient stays are often ill because of concomitant cancer or surgery. Bleeding or failure of anticoagulation requiring placement of a vena caval filter may complicate their clinical
29
clinical CORNERSTONE
.
DEEPVENOUSTHROMBOSIS
1 Vol.2 No.4
and chills usually suggest cellulitis rather than DVT, although DVT may be present concomitantly. Nevertheless, clinicopathologic conferences often try to trick invited discussants by selecting cases of DVT that present as fever of unknown origin. Do not assume that patients receiving prophylactic heparin are always protected from DVT. In fact, such patients are susceptible to massive DVT, often bilateral, if heparin-induced thrombocytopenia develops during heparin administration. (Heparin-induced thrombocytopenia is more likely to occur if unfractionated heparin is used rather than low-molecular-weight heparin.) It is ironic that heparin-induced thrombocytopenia is associated with clotting rather than bleeding. In fact, if bleeding occurs in the presence of thrombocytopenia, the cause of the low platelet count is probably not related to heparin use.
course. In this ill population, the mortality rate at 3 months may approach 20%. DVT may first be suspected simply by an ominous clinical setting such as recent trauma, surgery, or immobilization from a long airplane flight. Contributing risks include a past history or family history of DVT as well as a previously diagnosed hypercoagulable state such as factor V Leiden, hyperhomocystinemia, or anticardiolipin antibodies. Marked obesity and cigarette smoking also increase the risk of DVT. Upper-extremity venous thrombosis, in particular, is associated with indwelling central venous catheters, hypercoagulable states, and a history of DVT of the leg. From a women’s health perspective, pregnancy, oral contraceptives, and hormone replacement
Physical Examination When DVT is detected early after onset, the physical findings may be minimal, consisting of mild palpation discomfort in the lower calf. At the other end of the spectrum is massive thigh swelling and marked tenderness when palpating the inguinal area over the course of the femoral vein. Such patients often have difficulty walking and may require a cane, crutches, or walker. Erythema usually suggests concomitant superficial venous phlebitis with saphenous vein involvement or coexisting cellulitis. If a patient has upper-extremity venous thrombosis, there may be asymmetry in the supraclavicular fossae or in the girth of the upper arms. Also, look for a prominent superficial venous pattern over the anterior chest wall. A respiratory rate (count it yourself) that exceeds 16 respirations per minute, coupled with labored breathing, should suggest that a portion of the suspected DVT has already embolized to the lungs. If the workup for DVT proves negative, an investigation for PE should be undertaken. If the leg is diffusely edematous, DVT is an unlikely diagnosis. Much more common is an acute exacerbation of venous insufficiency due to postphlebitic syndrome. Under extreme and rare circumstances venous ulceration can occur. The
will double or triple the risk of DVT. Fortunately, the absolute incremental risk is low (no more than 1 additional DVT per 1000 woman-years). It is important to recognize that as many as half of the patients with DVT may have no symptoms or signs. Therefore, maintaining a high level of clinical suspicion is of paramount importance.
History Discomfort that was at first intermittent becomes persistent; swelling may ensue. The patient who seeks medical attention may know someone who has suffered DVT but may be reluctant to state that DVT is feared. The most common story told by patients with DVT is of a cramp or charley horse in the lower calf that does not abate after several days; in fact, it gradually worsens. Certain features of a history argue against DVT. The discomfort from DVT rarely has an abrupt onset. Sudden, excruciating calf discomfort is most likely due to a ruptured Baker’s cyst. Fever
30
clinical CORNERSTONE
= DEEPVENOUSTHROMBOSIS
* Vol.2 No.4
Active cancer (treatment ongoing, or within previous 6 months, or palliative) Paralysis, paresis, or recent plaster immobilization
of the lower extremities
Recently bedridden for >3 days or major surgery within 4 weeks Localized
tenderness along the distribution
of the deep venous system
Entire leg swollen Calf swelling by >3 cm when compared with the asymptomatic
leg (measured
10 cm below tibia1 tuberosity) Pitting edema (greater in the symptomatic Collateral Alternative
superficial
1 leg)
1
veins (nonvaricose)
1
diagnosis as likely as or greater than that of deep vein thrombosis
-2
*Note: In patients with symptoms in both legs, the more symptomatic leg should be used. High pretest probability = 23 points; moderate pretest probability = l-2 points; low pretest probability = zero or negative points. Reprinted with permission from Wells PS, Anderson D, Bormanis J, et al. Value of assessment of pretest probability vein thrombosis in clinical management. Luncet. 1997;350:1796.
distinction between venous insufficiency and acute DVT is crucial. The former condition is managed with vascular compression stockings alone; the latter problem requires immediate administration of anticoagulants.
of deep-
Doppler imaging, is known as duplex sonography and is the principal diagnostic imaging test for suspected acute DVT. Sonographic evaluation utilizes compression ultrasound along the full length of the femoral, popliteal, and calf veins. The transducer is held transverse to the vein, and normally, the vein collapses with gentle manual compression. The compressed vein appears as if it is winking. The main criterion for diagnosing DVT is lack of compression of a deep vein. This diagnosis can be confirmed by direct visualization of thrombus on ultrasound or by abnormal venous flow on Doppler examination (eg, loss of physiologic respiratory variation or loss of the expected augmentation of blood flow during calf compression). Among symptomatic patients, duplex sonography is very accurate, with high sensitivity and specificity (Figure 1). Its sensitivity decreases when assessing patients with isolated calf DVT or asymptomatic patients. Major limitations include inability in most situations to directly image pelvic vein thrombosis and difficulty diagnosing acute superimposed on chronic DVT. I do not advocate a strategy of serial ultrasonographic testing when results are equivocal. In these circumstances I
Clinical Modeling of Pretest Probability A Canadian group developed and tested a clinical model to predict the pretest probability for DVT. It relies on a scoring system with 9 parameters that can be quickly assessed based on the clinical setting, history, and physical examination (Table). Four of 9 parameters focus on clinical setting and history, while the other 5 depend on the physical examination of the legs. Results are then tabulated into 3 categories depending on the final score: high, moderate, and low pretest probability for DVT. I believe this modeling is useful as a reminder of the components of DVT workup other than imaging tests. However, I do not personally use this scoring system in my daily practice.
IMAGING TESTS Venous Ultrasonography Venous ultrasonography, combined with color
31
clinical CORNERSTONE
.
QEEPVENOUSTHROMBOSIS
q
Vol.2 No.4
The principal problem with this approach is low sensitivity of IPG, even for massive nonobstructing DVT, and a high false-negative rate. I believe that IPG should no longer be used for routine evaluation of patients with suspected acute DVT.
Contrast Venography Although contrast venography has traditionally been considered the gold standard for DVT diagnosis, many specialists now believe that duplex sonography and MRI are more accurate. Contrast venography does not yield a definitive diagnosis when there is total obstruction of the deep venous system because the contrast agent cannot gain access to the occluded segment. Furthermore, I can personally attest to the difficulty in interpreting the results of calf venography because there are myriad tiny and overlapping veins to analyze. Despite its limitations, a properly performed contrast venogram is beautiful to behold (Figure 2). It can show clearly a meniscus of fresh thrombus. It can define the extent and precise anatomical location of the DVT. The venogram can also demonstrate the presence of collaterals and can provide firm indications of whether the patient has suffered previous venous disease. Finally, the venogram
Figure 1. Venous ultrasound with color Doppler imaging of the proximal right leg veins at the junction of the superficial femoral vein (SFV), which despite its name, is a deep leg vein, and the profunda (deep) femoral vein (PFV) as they merge into the common femoral (CF) vein. In the original venogram, color flow is normal (red) in the femoral artery and normal (blue) in the PFV There is no thrombus in the PFR However, the SFV contains a totally obstructing thrombus (arrowheads).
prefer to select an alternative diagnostic modality such as magnetic resonance imaging (MRI) or contrast venography.
Impedance Plethysmography This diagnostic method assesses electrical conductivity by measuring the resistance (impedance) to a weak current passed through the leg. This weak current is imperceptible to the patient and is incapable of stimulating the heart. Normally, conductivity increases (as the impedance decreases) while blood accumulates during inflation of an impedance plethysmography (IPG) cuff around the calf. Conversely, conductivity decreases (as the impedance increases) when blood drains from the calf during IPG cuff deflation. These electrical changes are reduced in patients with DVT.
can demonstrate abnormal connections between the superficial and deep venous systems typical of patients with venous insufficiency. Contrast venography is an uncomfortable, invasive test. It causes a chemical phlebitis in about 1% of patients. One must always keep in
32
cUnical CORNERSTONE
m DEEPVENOUSTHROMBOSIS
= Vol.2 No.4
Figure 3. Magnetic resonance image of a normal popliteal vein, demonstrating the extraordinary resolution and detail that can be obtained with this imaging method. Reprinted with permission from Wolfe MU: Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment Curr Probl Cardiol. with thrombolytic therapy. 1993; 10:585-636.
Figure 2. Contrast venogram of the leg. Contrast tracks between the large popliteal vein thrombus and the vessel wall, creating the “tram-track” sign of an acute DVT. The proximal aspect of the thrombus is convex. Reprinted with permission from Wolfe MW Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment Curr Probl Cardiol. with thrombolytic therapy. 1993;10:585-636.
Contrast venography, ironically, is undergoing a renaissance as interventional angiographers select patients with massive iliofemoral DVT or recurrent DVT who require laboratory procedures such as catheter-directed thrombolysis, suction or rotational catheter thrombectomy, venous angioplasty, or venous stenting. When these procedures are required, contrast venography is a necessity.
mind the possibility of allergy to the contrast agent and to worsening renal function in patients with baseline renal insufficiency. For these latter patients, ask your angiographer to consider using carbon dioxide gas rather than standard contrast as the imaging agent. Furthermore, a “Catch-22” situation has evolved in which trainees receive very little experience in performing and interpreting contrast venography. Therefore, when a high-quality contrast venogram is required, skilled operators are difficult to find for this diagnostic study, and it has become a lost art.
Magnetic Resonance Imaging Use of MRI depends on the resources, interest level, and skill of the radiologists at your hospital. When properly performed, this noninvasive test can provide surprisingly precise, detailed information about the venous system (Figure 3). MRI can also help estimate the age of a thrombus based on various “spin” characteristics of the image. I find MRI especially useful in assessing suspected pelvic vein
33
dinid
CORNERSTONE
n
DEEPVENOUSTHROMBOSIS
n
Vol. 2 No. 4
Figure 4. Diagnostic algorithm for DVT A4RI = magnetic resonance imaging.
thrombosis and in defining the extent of upperextremity vein thrombosis.
Nuclear Venography In 1998, the US Food and Drug Administration approved technetium-99m-apcitide for the diagnosis of acute leg DVT. A complex of the synthetic peptide (apcitide) and the radionuclide (technetium) binds preferentially to the glycoprotein IIb/IIIa receptors found on activated platelets. This diagnostic method may be complementary to ultrasonography and provide information on pelvic vein thrombosis (not ordinarily imaged by ultrasound), acute superimposed upon chronic DVT (poorly differentiated by ultrasound), and acute DVT when the ultrasound examination is technically limited due to body habitus or ambiguous findings. Broad clinical experience with this technique is not yet available, however.
OVERALL DIAGNOSTIC ALGORITHM FOR DVT The first step in a diagnostic algorithm (Figure 4) for DVT is suspecting this disease entity based on the clinical setting, symptoms, and signs elicited from evaluation of the patient. The initial imaging test should be venous ultrasonography, with color Doppler imaging if available. If positive, treatment
34
clinical CORNERSTONE
.
DEEPVENOUSTHROMBOSIS
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Cogo A, Lensing AWA, Koopman MMW, et al. Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;3 16: 17-20. Cornuz J, Pearson SD, Polak JF. Deep venous thrombosis: complete lower extremity venous US evaluation in patients with known risk factors-outcome study. Radiology. 1999;211:637-641.
for DVT should commence. In most instances, therapy will consist of anticoagulation alone. Under some circumstances, however, a more interventional approach will be required with mechanical intervention or catheter-directed thrombolysis. To perform these procedures, contrast venography will be necessary. If duplex sonography is negative, the workup for DVT can usually be discontinued. The only caveat is to continue the investigation for DVT in the presence of very high clinical suspicion despite a negative ultrasound examination. Such patients
de Moerloose P, Michiels JJ, Bounameaux H. The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism. Semin Thromb Hemost. 1998;24:409412. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest. 1998;114:5618-5788.
would have classic historical features and physical examination findings for DVT. The workup should also continue if the ultrasound results are equivocal. This is often the case in patients with marked obesity, leg edema, or pain upon leg palpation in whom a technically adequate study simply cannot be obtained. Under these circumstances, further imaging should
Ibrahim S, MacPherson DR, Goldhaber SZ. Chronic venous insufficiency: mechanisms and management. Am Heart J. 1996;132:856860.
proceed either with contrast venography or MRI.
Kahn SR. The clinical diagnosis of deep venous thrombosis. Integrating incidence, risk factors, and symptoms and signs. Arch Intern Med. 1998;158:2315-2323.
Jongbloets LMM, Lensing AWA, Koopman MMW, et al. Limitations of compression ultrasound for the detection of symptomless postoperative deep vein thrombosis. Lancet. 1994;343:1142-1144.
SUMMARY
This imaging test is widely available and
Kearon C, Ginsberg JA, Hirsh J. The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Ann Intern Med. 1998;129:1044-1049.
can generally be performed with high-quality results. It facilitates and simplifies the management of patients who may be afflicted with this morbid and potentially fatal disease.
Piccioli A, Prandoni P, Goldhaber SZ. Epidemiologic characteristics, management, and outcome of deep venous thrombosis in a tertiary-care hospital: The Brigham and Women’s Hospital DVT Registry. Am Heart J. 1996;132:1010-1014.
SUGGESTED
Prandoni P, Polistena P, Bernardi E, et al. Upperextremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med. 1997;157:57-62.
High-resolution
venous ultrasonography
has revo-
lutionized the diagnostic algorithm for acute DVT.
READING
Anand SS,Wells PS, Hunt D, et al. Does this patient have deep vein thrombosis? JAMA. 1998;279:1094-1099.
Simons GR, Skibo LK, Polak JF, et al. Utility of leg ultrasonography in suspected symptomatic isolated calf deep venous thrombosis. Am J Med. 1995;99:43-47.
Anderson DR, Wells PS. Improvements in the diagnostic approach for patients with suspected deep vein thrombosis or pulmonary embolism. Thromb Huemost. 1999;82:878-886.
Warkentin TE. Heparin-induced thrombocytopenia: a ten-year retrospective. Annu Rev Med. 1999;50:129-147. Wells PS, Anderson D, Bormanis J, et al. Value of assessmentof pretest probability of deep-vein thrombosis in clinical management. Luncet. 1997;350:1795-1798.
Birdwell BG, Raskob GE, Whitsett TL, et al. The clinical validity of normal compression ultrasonography in . outpatients suspected of having deep vein thrombosis. Ann Intern Med. 1998;128:1-7.
Wolfe MW, Skibo LK, Goldhaber SZ. Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment with thrombolytic therapy. Curr Probl Cardiol. 1993;10:585%636.
Bundens WP, Bergan JJ, Halasz NA, et al. The superficial femoral vein. A potentially lethal misnomer. JAMA. 199.5;274:1296-1298.
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