INTRODUCTION — Lower extremity deep venous thrombosis (DVT) and pulmonary embolism are two manifestations of venous thromboembolism. Given the risks associated with untreated lower extremity DVT (eg, [fatal] pulmonary emboli) and the risk of anticoagulation (eg, major or life-threatening bleeding), accurate diagnosis of DVT is essential.
The approach described in this topic applies to nonpregnant adults. The evaluation of pregnant women with suspected DVT and the treatment of DVT are discussed separately. (See "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis", section on 'Diagnostic algorithm' and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)
CLINICAL PRESENTATION — Features of lower extremity DVT are nonspecific and many patients are asymptomatic.
History — DVT should be suspected in patients who present with leg swelling, pain, warmth, and erythema [1-3]. In one series, the sensitivity and specificity of these findings were [4]:
●Swelling or edema – 97 and 33 percent
●Pain – 86 and 19 percent
●Warmth – 72 and 48 percent
Symptoms are usually unilateral but can be bilateral. Symptoms are confined to the calf in patients with isolated distal DVT, while patients with proximal DVT may have calf or whole leg symptoms. Iliac vein thrombosis may be suspected if patients present with massive swelling of the proximal part of the leg and buttock pain. Phlegmasia cerulea dolens (PCD) is an uncommon form of massive proximal DVT and is discussed separately. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Special populations'.)
Common risk factors for DVT that should be sought in all patients include (table 1):
●History of immobilization or (prolonged) hospitalization
●Recent surgery or trauma (typically within 12 weeks of surgery or trauma)
●Obesity
●Previous venous thromboembolism (VTE)
●Malignancy or constitutional symptoms suggestive of malignancy
●Use of oral contraceptives or hormone replacement therapy
●Pregnancy or postpartum status
●Stroke with hemiplegia or immobility
●Age >65 years
●Family history of VTE
●Heart failure
●Inflammatory bowel disease
Less common risk factors include collagen-vascular and myeloproliferative disorders, nephrotic syndrome, and heparin-induced thrombocytopenia. Left-sided DVT may indicate the presence of May-Thurner syndrome (thrombosis of the left iliac vein due to compression from the overlying right iliac artery). These and other VTE risk factors are discussed separately. (See "Overview of the causes of venous thrombosis" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors", section on 'History and examination'.)
Physical examination — Although often unrevealing, a physical examination of the legs, abdomen, and pelvis should be performed in patients with suspected DVT to look for the following:
●Dilated superficial veins
●Unilateral edema or swelling with a difference in calf or thigh circumferences
●Unilateral warmth, tenderness, erythema
●Pain and tenderness along the course of the involved major veins (figure 1)
●Local (eg, inguinal mass) or general signs of malignancy
Among these, a larger calf circumference is the most useful finding. One meta-analysis reported that patients with a difference in calf circumference were twice as likely to have DVT [5]. Homans' sign (calf pain on passive dorsiflexion of the foot) is unreliable for the presence of DVT.
An evaluation for underlying risk factors for DVT and for evidence of PE (eg, dyspnea, pleuritic chest pain) should be performed, the details of which are discussed separately. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation'.)
Laboratory — Routine laboratory tests (eg, complete blood count, chemistries, liver function tests, coagulation studies) are not useful diagnostically, but may provide clues as to the underlying cause and may influence treatment decisions if DVT is confirmed. (See "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors", section on 'Laboratory tests and imaging'.)
SUSPECTED FIRST DVT (RISK STRATIFICATION) — Several diagnostic approaches for patients with a suspected first DVT of the lower extremity have been proposed, none of which are foolproof. We prefer approaches that incorporate clinical assessment of the pretest probability (PTP) (see 'Assessment of clinical pretest probability' below) and D-dimer testing in selected patients (see 'D-dimer' below). This approach allows for the strategic use of ultrasonography for diagnosis (see 'Diagnostic ultrasonography suspected first DVT' below). Alternative imaging modalities are available (eg, computed tomographic or magnetic resonance imaging [MRI] venography); they may be helpful in patients with clinically suspected ipsilateral recurrent DVT. (See 'Alternative imaging' below.)
The goal of diagnostic testing is to "rule-in" (>85 percent post-test probability of DVT) or "rule out" DVT (<2 percent post-test probability of venous thromboembolism [VTE] in the next three months) with an acceptable level of certainty, thereby justifying instituting or withholding anticoagulant therapy, respectively [6].
Our approach is in general consistent with approaches outlined by several international guidelines and societies [6-8].
Assessment of clinical pretest probability — In patients with suspected first DVT, we suggest estimation of the clinical PTP. Subsequent measurement of the D-dimer level and compression ultrasonography are dependent upon the assigned PTP of DVT. Gestalt estimates of PTP may be facilitated/supplemented by prediction rules such as the Wells or modified Wells score (see 'Wells and modified Wells score' below). Choosing how to assess PTP is often dependent upon clinician preference as neither gestalt estimates nor prediction rules have been conclusively proven to be superior to the other. While we typically prefer to assign patients to three risk categories (low; moderate; high), assigning patients to two categories (unlikely; likely) is also appropriate. (See 'Diagnostic ultrasonography suspected first DVT' below and 'D-dimer' below.)
Wells and modified Wells score — While there are several PTP scoring systems available, the Wells score is the best studied [3,9-19].
●Wells Score – Components of the Wells score include the following (calculator 1) (table 2) [11]:
•Paralysis, paresis, or recent orthopedic casting of a lower extremity (1 point)
•Recently bedridden for longer than three days or major surgery within the past four weeks (1 point)
•Localized tenderness in the deep vein system (1 point)
•Swelling of an entire leg (1 point)
•Calf swelling 3 cm greater than the other leg, measured 10 cm below the tibial tuberosity (1 point)
•Pitting edema greater in the symptomatic leg (1 point)
•Collateral nonvaricose superficial veins (1 point)
•Active cancer or cancer treated within six months (1 point)
•Alternative diagnosis more likely than DVT (eg, Baker's cyst, cellulitis, muscle damage, postphlebitic syndrome, inguinal lymphadenopathy, external venous compression) (minus 2 points)
The total score in an individual patient denotes the following risk of DVT:
•0 or less points – Low probability (see 'Low-probability' below)
•1 to 2 points – Moderate probability (see 'Moderate-probability' below)
•3 to 8 points – High probability (see 'High-probability' below)
The Wells score was best validated in a prospective study of 593 patients with suspected first DVT (in a subspecialty outpatient setting) [11]. The overall incidence of venographic-confirmed DVT was low, at 15 percent, with the following rates according to the probability of DVT:
•Low probability – 3 percent
•Moderate probability – 17 percent
•High probability – 50 to 75 percent
The scoring system may be less useful in a primary care or inpatient setting [5,20,21]. One prospective study of 1295 patients with suspected DVT who presented to primary care practices reported a higher rate of DVT in patients with a low probability of DVT (12 percent), when compared with the expected rate of 3 percent [20]. A meta-analysis of 51 studies also reported reduced performance of the score in patients who were older, had a prior DVT, or had other comorbidities [5].
●Modified Wells score – The modified Wells score contains all the components of the original Wells score, with one additional point given to those with a history of previously documented DVT [22]. The modified score classifies patients according to whether or not DVT is likely (a score of two or greater) or unlikely (a score of one or less) (calculator 2) (table 2). Use of the modified Wells score was best studied in an algorithm that included measurement of D-dimer [22], which is discussed below. (See 'D-dimer' below.)
Low-probability — In patients with a low PTP for first lower extremity DVT (ie, approximately 3 percent) (calculator 1) (table 2), we suggest that a high- or moderate-sensitivity D-dimer test be performed. D-dimer should not be done if it is expected to be positive due to another condition (eg, after recent surgery) (table 3); instead, these patients can proceed directly to ultrasonography (US). (See 'Assessment of clinical pretest probability' above and 'D-dimer' below.)
The subsequent approach is the following:
●Normal D-dimer level (<500 ng/mL) – Patients with a low PTP in whom the D-dimer level is normal do not need further testing. (See 'D-dimer' below.)
●Positive D-dimer level (>500 ng/mL) – Patients with a low PTP in whom the D-dimer is positive, whole leg ultrasonography or proximal compression ultrasonography (CUS) should be performed. Choosing among these options is discussed below (see 'Diagnostic ultrasonography suspected first DVT' below and 'Choosing proximal or whole leg ultrasonography' below):
•Positive ultrasonography – Patients should be treated if:
-Proximal DVT is identified (by either whole leg ultrasonography or proximal CUS) or
-Distal DVT is identified (on whole leg ultrasonography) and the patient meets the criteria for the treatment of distal DVT
What constitutes positive ultrasonography, treatment options for DVT, and the indications for treating isolated distal DVT are discussed separately. (See 'Positive' below and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'.)
•Negative ultrasonography – If whole leg ultrasonography or proximal CUS is negative for DVT, no further testing is required. What constitutes negative US and factors that influence US choice are discussed separately. (See 'Negative' below and 'Choosing proximal or whole leg ultrasonography' below.)
•Nondiagnostic ultrasonography – Nondiagnostic studies are rare. Further investigation based upon nondiagnostic findings are discussed below. (See 'Nondiagnostic' below.)
Moderate-probability — In patients with a moderate PTP for first lower extremity DVT (ie, approximately 17 percent) (calculator 1) (table 2), we suggest that a high-sensitivity D-dimer test be performed. D-dimer should not be done if it is expected to be positive due to another condition (eg, after recent surgery) (table 3); instead, these patients can proceed directly to ultrasonography. As an alternative to this approach, some experts proceed directly to ultrasonography without D-dimer testing. The decision is influenced by factors including US availability and whether US testing will evaluate other diagnoses (eg, Baker's cyst). (See 'Assessment of clinical pretest probability' above.)
The subsequent approach is the following:
●Normal D-dimer level (<500 ng/mL) – Patients with a moderate PTP and a normal D-dimer level measured using a high-sensitivity assay do not need further testing. Negative moderately-sensitive assays, are considered insufficient for ruling out DVT, the details of which are discussed below. (See 'D-dimer' below.)
●Positive D-dimer level (≥500 ng/mL) – If the D-dimer level is positive, whole leg ultrasonography or proximal CUS should be performed. Choosing among these two options is discussed separately (see 'Diagnostic ultrasonography suspected first DVT' below and 'Choosing proximal or whole leg ultrasonography' below):
•Positive ultrasonography – Patients should be treated if:
-Proximal DVT is identified (by either whole leg ultrasonography or proximal CUS) or
-Distal DVT is identified on whole leg ultrasonography and the patient meets the criteria for the treatment of distal DVT
What constitutes a positive scan, treatment options for DVT, and the indications for treating isolated distal DVT are discussed separately. (See 'Positive' below and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'.)
•Negative ultrasonography – If whole leg ultrasonography is negative (ie, neither proximal nor distal DVT is identified), no further testing is required.
If proximal CUS is negative, options include whole leg examination to evaluate the distal veins OR repeat proximal CUS at one week (typically off anticoagulation) to detect possible extension of distal DVT into the proximal veins. No further testing is necessary if whole leg or repeat proximal ultrasonography is negative; however, patients should be treated if proximal DVT is identified OR if distal DVT is identified and the patient meets the criteria for the treatment of distal DVT. What constitutes a negative US study and data that support serial proximal CUS are discussed separately. (See 'Diagnostic ultrasonography suspected first DVT' below and 'Negative' below.)
The approach to those with nondiagnostic ultrasonography is discussed below. (See 'Nondiagnostic' below.)
High-probability — In patients with a high PTP for first lower extremity DVT (approximately 50 to 75 percent prevalence of DVT) (calculator 1) (table 2), we suggest that proximal CUS or whole leg ultrasonography be performed. Unlike patients with a low or moderate PTP, D-dimer cannot be reliably used to exclude DVT in this population. Factors that influence whether proximal or whole leg ultrasonography is chosen are discussed separately. (See 'Assessment of clinical pretest probability' above and 'Diagnostic ultrasonography suspected first DVT' below and 'Choosing proximal or whole leg ultrasonography' below.)
The subsequent approach is the following:
●Positive ultrasonography – Patients should be treated if proximal DVT is identified (by either whole leg or proximal ultrasonography) OR if distal DVT is identified on whole leg ultrasonography and the patient meets the criteria for the treatment of distal DVT. What constitutes a positive scan, treatment options for DVT, and the indications for treating isolated distal DVT are discussed separately. (See 'Positive' below and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)" and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'.)
●Negative CUS – If whole leg ultrasonography is negative, no further testing is generally necessary. However, if iliac vein thrombosis is suspected, then iliac vein ultrasonography should be performed. If iliac vein US is nondiagnostic (eg, due to overlying bowel or obesity), computed tomographic (CT) venography should be performed (see 'Alternative imaging' below), which may also help identify an alternate etiology. In patients with negative imaging who remain symptomatic and do not have an alternative diagnosis, repeat US testing in 24 hours is appropriate. What constitutes a negative scan and factors that influence ultrasonography choice are discussed separately. (See 'Negative' below.)
If proximal CUS is negative, options include high sensitivity D-dimer level measurement, repeat proximal CUS at one week (earlier if suspicion is very high; typically off anticoagulation), whole leg ultrasonography, or iliac vein ultrasonography. Choosing among these options should be individualized. As an example, D-dimer may be preferred in patients who cannot return for repeat ultrasonography, while repeat proximal CUS may be preferred if the D-dimer is expected to be elevated due to another condition (table 3). Similarly, whole leg ultrasonography may be preferred in patients with symptoms suggestive of calf DVT, or in patients who cannot return for testing, and iliac vein duplex ultrasonography or CT venography may be preferred in those in whom iliac vein thrombosis is suspected (eg, those with extensive leg swelling or anatomic abnormality of the pelvis). In general, if one or more of these tests are negative, then no further testing is required, while the identification of DVT should prompt treatment. A positive D-dimer should prompt repeat proximal CUS or whole leg ultrasonography (if not already performed) and/or iliac vein imaging. (See "Overview of the causes of venous thrombosis", section on 'Anatomic risk factors for deep venous thrombosis'.)
Although nondiagnostic scans are rare, further testing is individualized and discussed separately. (See 'Nondiagnostic' below.)
D-dimer — D-dimer, a degradation product of cross-linked fibrin, is elevated in nearly all patients with acute DVT (ie, it is highly sensitive). However, it is nonspecific since elevated levels are found in many other conditions (eg, malignancy, sepsis, recent surgery or trauma, pregnancy, renal failure) (table 3) [6,23-34]. Using a validated D-dimer assay, a negative result (eg, <500 ng/mL) is useful for ruling out DVT, particularly in those with a low or moderate pre-test probability (PTP) for thrombosis; however, a negative test is obtained in about 30 percent of outpatients (lower in inpatients or if there has been a previous VTE). A positive result (eg, ≥500 ng/mL) is not diagnostic and indicates the need for further investigation.
Studies consistently report a high sensitivity and poor specificity of D-dimer in patients with acute DVT [6,35-41]. Cutoff values and assay type vary among laboratories. Clinicians should be aware of whether a "high sensitivity" or "moderate sensitivity" assay is being used in their institution. In general, "high sensitivity" assays can reliably rule out DVT in a patient with low and moderate PTP for DVT while "moderate sensitivity" assays are only useful for ruling out DVT in those with low PTP for DVT. D-dimer testing is of limited value in patients with high PTP since the negative predictive value is lower in this population.
Best illustrating the high sensitivity of D-dimer in patients with acute DVT is a meta-analysis of 217 studies that reported the highest sensitivity associated with the following D-dimer assays: enzyme-linked immunofluorescent assays (ELISA; 96 percent), microplate ELISA (94 percent), and semiquantitative or immunoturbidimetric assays (93 percent) (also known as "high sensitivity" D-dimer assays) [6]. In contrast, whole blood D-dimer and latex semiquantitative assays were less sensitive (83 to 85 percent; ie, "moderate sensitivity" D-dimer assays). Although moderate sensitivity D-Dimer assays are more specific than high sensitivity assays, they have a lower negative predictive value. Among outpatients who are suspected of having DVT, high sensitivity tests are negative in about 30 percent and moderately sensitive tests are negative in about 60 percent without thrombosis.
D-dimer values rise with age, further hampering specificity in older patients [24,42-45]. Using a higher D-dimer cutoff in older patients improves its diagnostic utility and specificity [44-47]. One meta-analysis of 13 cohorts (12,497 patients) compared the specificity of conventional cutoff values for D-dimer (<500 ng/mL) to age-adjusted values (defined as age [years] x 10 ng/mL for patients aged over 50 years) [45]. Compared with a conventional cutoff value, higher specificities were reported for age-adjusted cutoff values (age 51 to 60 years: 63 versus 58 percent; 61 to 70 years: 50 versus 39 percent; 71 to 80 years: 44 versus 24 percent; >80 years: 35 versus 15 percent). While age-adjusted D-Dimer cutoffs are being increasingly used, there is no consensus on the validity of this practice and use is variable among institutions.
Importantly, the D-dimer assay should not be used as a stand-alone test in patients suspected of having DVT, but rather should be used in conjunction with clinical PTP and/or ultrasonography [27,31,40,41,48-55]:
●A D-dimer level less than 500 ng/mL in conjunction with a low to moderate probability of DVT is useful in excluding DVT without the need for ultrasonography [22,24,36,41,51,56-64]. This was best illustrated in a trial of 1096 patients with suspected DVT who were classified according to the modified Wells criteria as DVT "likely" or DVT "unlikely" [22] (calculator 2) (table 2) (see 'Wells and modified Wells score' above). The patients were then randomly assigned to undergo routine ultrasonography (control group), or to only have imaging if they had an unlikely PTP and a positive D-dimer or if they had a likely PTP (D-dimer group). D-dimer testing resulted in a significant reduction in the use of ultrasonography (0.78 versus 1.34 tests per patient); almost 40 percent of patients in the D-dimer group did not require ultrasonography. For patients in whom DVT was ruled out by the initial diagnostic strategy, there was no difference in the frequency of VTE during three months of follow-up (0.4 versus 1.4 percent in the D-dimer and control groups, respectively).
●Several studies have reported that a D-Dimer level less than 500 ng/mL also obviates the need for serial proximal ultrasonography in those with an initial negative ultrasound [65-67]. As an example, a study of 810 patients with suspected DVT and negative ultrasonography on initial testing found that the six-month rate of thromboembolism was similar in patients with a negative D-dimer (2.1 percent) and those with a negative repeat ultrasonography at one week (1.3 percent) [67].
●A "PTP-adjusted" approach to D-dimer interpretation has been prospectively studied in patients with suspected DVT [68]. Using a selective D-dimer strategy that excluded DVT when D-dimer levels were <1.0 microg/mL in those with low PTP or <0.5 microg/mL in those with moderate PTP, reduced the need for ultrasonography by 8 percent in outpatients suspected as having DVT and by 21 percent in those with low PTP.
●In one study of 1508 patients with suspected DVT, DVT was excluded in patients with Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL [55]. All other patients had proximal ultrasonography. Using this strategy, only 0.6 percent of those in whom DVT was excluded developed DVT during follow-up. It was estimated that this strategy reduced the need for imaging by 47 percent (1.36 scans/patient to 0.72 scans/patient), when compared with a traditional strategy. While encouraging, further study is needed to validate this approach.
ALTERNATE APPROACHES — For patients who are not initially stratified according to clinical pretest probability (PTP) of low, moderate, or high risk the initial test of choice is ultrasonography (US). Choosing among whole leg ultrasonography or proximal compression ultrasonography (CUS) is discussed separately. (See 'Choosing proximal or whole leg ultrasonography' below.)
Patients should be treated if proximal DVT is identified (by either whole leg or proximal ultrasonography) OR if distal DVT is identified on whole leg US and the patient meets the criteria for the treatment of distal DVT. (See 'Positive' below and "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)
When whole leg US is negative no further investigations are necessary unless iliac vein thrombosis is suspected. (See 'Negative' below.)
When the proximal CUS is negative, options include whole leg US (to detect distal DVT), repeat proximal CUS at three to seven days (to detect extension of distal DVT into the proximal veins), measuring a high-sensitivity D-dimer level, or assessing clinical PTP (low PTP excludes DVT with a negative proximal CUS). Choosing among these options involves similar principles to those described above for patients with a high probability DVT and negative proximal CUS. (See 'High-probability' above.)
The approach to those with a nondiagnostic ultrasonography is similar to that described above. (See 'Nondiagnostic' below and 'Low-probability' above.)
EMPIRIC ANTICOAGULATION — The decision to empirically anticoagulate while diagnostic testing is being performed depends upon the clinical suspicion for DVT and how soon diagnostic testing can be completed. Empiric anticoagulation is discussed separately. (See "Treatment, prognosis, and follow-up of acute pulmonary embolism in adults", section on 'Empiric anticoagulation'.)
DIAGNOSTIC ULTRASONOGRAPHY SUSPECTED FIRST DVT — Compression ultrasonography (CUS) with Doppler is the diagnostic test of choice in patients with suspected DVT.
Most of the data discussed in the sections below describe the diagnostic accuracy of CUS in outpatients with first suspected DVT. In general, the sensitivity and specificity of proximal CUS is greater than 95 percent. However, proximal CUS has limited utility and lower sensitivity in patients with the following [69-72]:
●Calf vein thrombus – Veins in the calf are harder to assess than proximal veins; proximal CUS does not image the calf veins while whole leg US images both the proximal and calf veins.
●Iliac vein thrombus – The iliac vein often cannot be assessed for compressibility and, consequently, these veins are also usually assessed with Doppler imaging or may require computed tomography (CT) venography. (See 'Alternative imaging' below.)
Our choices and interpretation of ultrasonography is in general in keeping with that of other experts [6,7,73]. However, based upon the same data, some experts have strong preferences for duplex rather than compression ultrasonography and whole leg rather than proximal vein ultrasonography [73]. Choosing among these options is often dependent upon the institutional policy and performing radiologist or ultrasound technician. Importantly, duplex ultrasonography has less accuracy than compression ultrasonography, since specificity of an abnormal duplex ultrasonogram is lower than that of an abnormal compression ultrasonogram. This topic does not discuss the accuracy of point-of-care-ultrasonography, which is not recommended for diagnosis unless the situation is urgent or emergent. (See "Indications for bedside ultrasonography in the critically ill adult patient", section on 'Vascular ultrasonography'.)
The interpretation of ultrasonography in those with suspected recurrent thrombus is discussed below. (See 'Ultrasonography interpretation' below.)
The term "free-floating" DVT is sometimes applied to thrombus that appears poorly adherent to the adjacent vessel wall. There are no strict diagnostic criteria for this phenomenon. It is reasonable to suggest that the risk of progression and embolization is similar to adherent thrombus and that it should be treated as such.
Choosing proximal or whole leg ultrasonography — Preference for proximal or whole leg ultrasonography varies among experts. While some experts prefer whole leg ultrasonography for most patients, others prefer confining the ultrasound examination to the proximal veins, down to and including the calf vein trifurcation. Alternatively, proximal ultrasonography may be done in most and whole leg ultrasonography in select subgroups (eg, those with prominent calf symptoms and negative proximal ultrasonography). Two-point proximal compression ultrasonography (femoral and popliteal vein) can usually be performed within 5 to 10 minutes, while whole leg compression ultrasonography usually takes 15 to 20 minutes. Although all approaches are acceptable, in practice the choice between proximal or whole leg ultrasonography is often institution-specific. Thus, it is important that clinicians know which test is performed at their institution and be familiar with its advantages and disadvantages. (See 'Assessment of clinical pretest probability' above and 'D-dimer' above.)
Both proximal and whole leg ultrasonography have a high sensitivity for the detection of proximal vein DVT (figure 1), which requires anticoagulant therapy to control symptoms, prevent progression and embolization, and to reduce the risk of post thrombotic syndrome, (ie, "clinically significant" DVT) (see 'Proximal' below). Whole leg ultrasonography will also detect isolated distal DVT; isolated distal DVT sometimes resolves or does not extend proximally without treatment and is associated with less severe complications (see 'Whole leg' below). Thus, routine use of whole leg ultrasonography has the potential to lead to the diagnosis of DVT that does not necessarily need to be treated. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT'.)
Proximal — Proximal vein CUS detects non-compressibility (indicative of thrombus) of the proximal veins (eg, common femoral, femoral, and popliteal veins (figure 1)) (see 'Positive' below). The identification of proximal DVT is clinically significant since it is more likely to progress and embolize compared with isolated distal DVT. Proximal vein CUS has a high sensitivity for the diagnosis of proximal vein DVT (>95 percent) and a high negative predictive value for ruling out proximal DVT in all patients, and for ruling out all DVT (including isolated distal DVT) in those with a low clinical pretest probability (PTP) for DVT (see 'Assessment of clinical pretest probability' above). In addition, compared to whole leg ultrasonography, proximal CUS is technically easier to perform and interpretation is less operator-dependent.
A limitation of proximal vein CUS is that, unlike whole leg ultrasonography, the calf veins are not imaged and, therefore isolated distal DVT cannot be detected. However, thrombus in this location rarely embolizes and anticoagulation is not always necessary in this population. In addition, the risk of missing clinically significant cases of distal DVT is minimized by the use of D-dimer and serial proximal CUS in select patients, the details of which are discussed separately. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT' and 'Suspected first DVT (risk stratification)' above.)
Several randomized trials and meta-analyses have consistently reported that proximal CUS (compared with contrast venography) is a sensitive test for proximal DVT (95 to 100 percent) [6,74-79]. For patients with a low probability for DVT, a single proximal CUS excludes the diagnosis, with rates of venous thromboembolism (VTE) during three months follow-up of about 0.5 percent [6]. For patients with a moderate to high probability for DVT who have a negative proximal CUS at initial presentation, approximately 2 percent have a proximal DVT when retested seven days later [80]. A single repeat study five to seven days after an initial negative study predicts a less than 1 percent likelihood of VTE over six months of follow-up in patients who have had anticoagulants withheld [81].
Compared with whole leg ultrasonography performed at initial presentation and serial proximal ultrasonography performed one week after initial presentation, randomized trials suggest that the rate of progressive VTE during follow-up is similar (about 1 to 2 percent) [77,82].
●In a trial that randomized 1002 patients with suspected DVT who could not have thrombosis excluded by clinical pretest probability and negative D-dimer testing to either serial proximal CUS (at initial assessment and at one-week follow-up) or to whole leg ultrasonography at initial assessment, there was a similar rate of progressive VTE during three months follow-up in those with negative tests who had anticoagulants withheld (2 versus 1 percent) [77].
●In another randomized trial that compared proximal and whole leg ultrasonography in a similar population, the rate of progressive VTE during three-months follow-up was similar (0.9 versus 1.2 percent) [82].
Whole leg — Similar to proximal vein CUS, whole leg ultrasonography detects proximal DVT (ie, common femoral, femoral, and popliteal veins) (figure 1) (see 'Positive' below). Its major advantage compared with proximal CUS is that, because it also images the veins in the calf (peroneal, posterior tibial, anterior tibial, and muscular veins), a negative test also excludes isolated distal DVT (ie, all DVT) and, therefore, there is no need for additional diagnostic testing and the need for repeat proximal CUS is eliminated.
However, compared with proximal CUS, whole leg ultrasonography is technically more difficult to perform and the interpretation is operator-dependent. In addition, the clinical significance of detecting isolated distal DVT is uncertain since they are at lower risk of embolizing, and not every patient needs treatment. The indications for anticoagulation in patients with distal DVT and the use of whole leg ultrasonography in patients with suspected DVT are discussed separately. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Distal DVT' and 'Suspected first DVT (risk stratification)' above.)
Data that support the high sensitivity (>99 percent) of whole leg ultrasonography in patients with suspected DVT include several randomized studies and meta-analyses (>99 percent) [76,82-89]. One meta-analysis of seven studies also reported that the three-month rate of VTE in patients who had anticoagulants withheld after a single negative whole leg ultrasound is very low (0.6 percent; 95% CI 0.25-0.89) [89]. Rates were 0.3 percent for those with low-probability DVT, 0.8 percent for patients with a moderate-probability DVT, and 2.5 percent for patients with a high-probability DVT.
Ultrasonography interpretation — Interpretation of CUS in patients with a first suspected DVT is described in the sections below. Interpreting CUS in patients with suspected recurrent DVT is discussed separately. (See 'Ultrasonography interpretation' below.)
Positive — Using ultrasound probe pressure, the presence of thrombus is diagnosed by demonstrating non-compressibility of the imaged vein. Veins that can be assessed for compressibility are the proximal (eg, the common femoral, femoral, and popliteal veins) and distal veins (eg, peroneal, posterior and anterior tibial, and muscular veins); iliac veins often cannot be assessed for compressibility (figure 1).
Prospective studies have demonstrated that lack of compressibility of a vein with the ultrasound probe is the most sensitive (>95 percent) and specific (>95 percent) sonographic sign for proximal vein thrombosis [74,90,91]. The addition of color flow Doppler does not improve the sensitivity, but can provide supportive evidence of thrombus and also help to identify calf veins [92,93]. Variation of venous size with the Valsalva maneuver has a low sensitivity and specificity for the diagnosis and is no longer performed in many centers.
In contrast, compression ultrasonography is less sensitive for the detection of calf vein and iliac vein thrombus since these veins are less readily compressed (particularly calf veins) [69-72].
Negative — A negative study is one that demonstrates full compressibility of all imaged veins.
Nondiagnostic — A nondiagnostic study is one where there is uncertainty about whether DVT is present or absent. Nondiagnostic findings are less common in outpatients compared with inpatients, with less than 5 percent of outpatients expected to have nondiagnostic findings of the proximal veins. Nondiagnostic findings are also less common when imaging the proximal veins compared with the distal veins (ie, with whole leg US); however, nondiagnostic findings that are confined to the distal veins are also less important and can usually be managed by withholding anticoagulant therapy while doing serial ultrasound testing. (See 'Suspected first DVT (risk stratification)' above.)
There are three main reasons for a nondiagnostic examination which often overlap.
●First, there may be difficulty visualizing the deep veins because of morbid obesity, edema, recent surgery or trauma, skin lesions, contractures, or leg casts (ie, technically-limited studies) [94].
●Second, although the deep veins are well visualized, small (eg, less than 5 cm long, or less than 2 mm wide) or atypical appearing abnormalities of uncertain significance may be identified [95].
●Third, in patients with previous DVT, when thrombus is present, it is often difficult to assess if it is new (acute) or old (residual thrombosis can persist indefinitely), the details of which are discussed separately. (See 'Ultrasonography interpretation' below.)
Further investigation(s) (eg, repeat proximal CUS at three and seven days) in those with nondiagnostic studies should be individualized and depend upon why the US is considered nondiagnostic, the extent and position of the venous segment (eg, distal or proximal veins) that is nondiagnostic, clinical PTP, results of D-dimer testing and the clinician's overall assessment of the risk associated with undiagnosed DVT.
SUSPECTED RECURRENT DVT — A previous episode of DVT is a known risk factor for a recurrent event. Patients with suspected recurrence present with similar symptoms and signs as those with a first event. However, persistent leg pain and swelling, which may fluctuate, is common after a first event (ie, postthrombotic syndrome [PTS]). The clinical features of DVT and PTS are provided separately. (See 'Clinical presentation' above and "Post-thrombotic (postphlebitic) syndrome", section on 'Clinical features'.)
The diagnostic evaluation of recurrence on the ipsilateral lower extremity is described in this section. The diagnosis of recurrence on the contralateral leg should follow the same approach as for patients with a suspected first event. (See 'Suspected first DVT (risk stratification)' above.)
Initial evaluation — For most patients with suspected recurrent ipsilateral DVT, proceeding directly to ultrasonography (proximal or whole leg ultrasonography) [6] or using an approach similar to that described for first suspected DVT is appropriate. (See 'Diagnostic ultrasonography suspected first DVT' above.)
Data to support either approach include the following:
●Prediction scoring systems such as the Wells criteria (table 2) (calculator 1) or the modified Wells (calculator 2) [61,96] can be used to reduce the number of unnecessary ultrasound scans as well as to guide management when scans are nondiagnostic. (See 'Suspected first DVT (risk stratification)' above and 'Ultrasonography interpretation' below.)
●Evidence suggests that, similar to patients with a first suspected event, a negative D-dimer level (eg, less than 500 ng/mL) is a sensitive diagnostic test and is, therefore, useful in excluding recurrence; however, when compared to patients with a first suspected event, the specificity is lower [22,96,97]. As examples:
•A prospective study of 105 patients with suspected recurrent DVT reported that D-dimer had a sensitivity of 97 percent, specificity of 30 percent, and negative predictive value of 95 percent [96]. However, the D-dimer was negative in only 17 percent of patients.
•In another prospective study of 300 patients with suspected recurrence and a negative D-dimer (45 percent of patients), the rate of DVT was less than 1 percent at three months in patients who had anticoagulant therapy withheld [97].
Ultrasonography interpretation — Thrombus resolves slowly with time, with a decrease in residual venous diameter (RVD) of about 50 to 60 percent over the first three months in the common femoral and popliteal veins [98]. About 80 percent of proximal ultrasound studies remain abnormal at three months, and about 25 to 50 percent are abnormal at one year [98-100]. Thus, when an abnormality is identified in patients with suspected recurrence, it may be difficult to determine whether it is due to old or new thrombus. Consequently, the specificity of ultrasonography for recurrence is lower than in patients with suspected first DVT. Although the specificity is improved when a previous ultrasound documents the extent of residual thrombosis, interobserver agreement remains variable and limited [101].
Previous ultrasonography — When there is a previous ultrasound for comparison, we and others agree that the following generally applies [6]:
●A positive ultrasound for acute thrombosis is one that demonstrates non-compressibility of a previously uninvolved venous segment (eg, popliteal or common femoral vein), an increase in compressed venous diameter ≥4 mm compared with the previous ultrasound, or evidence of a substantial extension of thrombus within the same venous segment (eg, 10 cm extension within the femoral vein) even though a new venous segment is not involved.
•Evidence of new non-compressibility of the proximal vein should be considered diagnostic of acute DVT, and patients should be treated, although only a minority (10 to 20 percent) of recurrent DVT are identified this way [98,102]. (See "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)".)
•Evidence of an increase in the RVD ≥4 mm and substantial (eg, >10 cm) thrombus extension are considered by most physicians as recurrent DVT. Although the optimal cut-off value for increase in RVD is uncertain, studies have reported that the specificity of an increase in RVD ≥2 mm was 95 percent, and ≥4 mm was 100 percent [98,103]. It has therefore been suggested that patients presenting with an increased RVD ≥4 mm be considered to have recurrent DVT [98,103,104].
●A negative study for acute thrombosis is one where there is full compressibility of all venous segments, or one with less than 2 mm increase in RVD of both the popliteal and common femoral vein compared with a previous compression ultrasound (CUS).
•If whole leg ultrasonography is negative for proximal and distal DVT, no further testing is required. If proximal CUS is negative, patients should undergo repeat proximal CUS at one week (occasionally a second CUS is performed), whole leg ultrasonography, or high sensitivity D-dimer level measurement (if not already performed). If any of these are negative, then no further testing is necessary. A positive D-dimer should prompt repeat proximal CUS, and a newly positive repeat CUS should prompt treatment.
•Patients with an increase in RVD <2 mm are unlikely to have recurrent DVT and should have repeat testing with proximal CUS, preferably after about two and seven days. A stable or improved repeat CUS does not need treatment, whereas evidence of growing thrombus is an indication for treatment.
The safety of diagnostic strategies that use RVD measurements on CUS to withhold anticoagulation when the CUS is compressible or reveals an increase in RVD <2 mm has been explored:
-A prospective study of 205 patients with suspected recurrent ipsilateral DVT compared proximal CUS findings with a CUS that had been performed after 3 to 12 months of anticoagulation [103]. Patients with a negative CUS (ie, non-compressibility or increased RVD <2 mm; n = 153) had serial testing at two and seven days, during which time anticoagulation was withheld; CUS converted to positive in 3 of the 153 patients. In the remaining 149 patients who remained off anticoagulant therapy, two (1.3 percent) had venous thromboembolism (VTE) during the next six months.
-In a similar study of 284 patients in whom recurrent DVT had been excluded using the same criteria and in whom anticoagulation was withheld, 3 percent developed VTE over the next three months [104].
-In a prospective study of 75 patients with suspected recurrence, when there was a negative D-dimer (<500 ng/mL) in addition to these ultrasound criteria, no patients developed VTE over the next three months [105].
●A nondiagnostic study is one with an increase in residual venous diameter ≥2 mm and <4 mm, or an extension in thrombus length that is <10 cm. Management of nondiagnostic studies should be individualized and involve an assessment similar to that described above (eg, pretest probability assessment, D-dimer, serial CUS, or venography). (See 'Nondiagnostic' above and 'Low-probability' above.)
No previous ultrasonography — In the absence of previous ultrasonography for comparison, the following generally applies:
●An ultrasound that demonstrated non-compressibility of the popliteal or common femoral vein indicates that there is either new or old thrombosis. New (ie, acute) thrombosis is more likely if: the thrombus is extensive; the vein is distended with little compressibility; D-dimer is positive, particularly if markedly elevated (eg, >2000 ng/mL); clinical pretest probability is high. If the overall assessment is that acute thrombosis is likely, patients are generally treated. If the overall assessment is that acute thrombosis is unlikely, anticoagulation can be withheld while serial ultrasonography (eg, two and seven days) is performed.
●A negative ultrasonography scan is one where all veins are fully compressible. (See 'Previous ultrasonography' above.)
●Management of nondiagnostic studies should be individualized and involve an assessment similar to that described above (eg, pretest probability assessment, D-dimer, serial CUS, or venography). (See 'Nondiagnostic' above and 'Low-probability' above.)
ALTERNATIVE IMAGING — For patients with suspected first or recurrent DVT contrast-enhanced computed tomographic venography (CTV) and magnetic resonance venography (MRV) are rarely used unless there is uncertainty about iliac vein or inferior vena cava thrombosis after ultrasonography. These diagnostic tests are considered less well validated, have associated complications of radiation (eg, CTV) and contrast exposure, and are more costly. They may be better than ultrasonography at distinguishing new from old thrombosis. While widely used in the past, ascending contrast venography, which was the gold standard for DVT diagnosis, and impedance plethysmography are now rarely used for diagnosis.
The technical aspects and diagnostic value of these modalities are discussed below:
●Computed tomography – Thrombus is usually identified on CT by demonstrating a filling defect with contrast-enhancement. The major disadvantage of CT is the potential for contrast-related complications or contraindications. (See "Contrast-associated and contrast-induced acute kidney injury: Clinical features, diagnosis, and management" and "Prevention of contrast-associated acute kidney injury related to angiography" and "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Introduction'.)
CT is not rigorously studied for the diagnosis of lower extremity DVT. Sensitivity and specificity data are derived from studies that combined CTV with a CT pulmonary angiogram (CTPA) in patients with suspected pulmonary embolism (PE) [27,106-109]. During CTPA, the subdiaphragmatic deep veins including those in the legs can be simultaneously imaged (during the venous phase of imaging), without the need for additional contrast. Although sensitivities as high as 95 percent for the diagnosis of femoropopliteal thrombus have been reported, data are derived from small case series; larger prospective studies are required before CT can be recommended to diagnose lower extremity DVT. (See "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Computed tomography pulmonary angiography'.)
●Magnetic resonance imaging – Although thrombus, which appears as a filling defect can be identified without contrast on MRV, the use of intravenous gadolinium is preferred. Magnetic resonance direct thrombus imaging (MRDTI) can diagnose lower extremity DVT based upon the altered characteristics of red blood cell methemoglobin within the imaged vein. In a prospective management outcome study of recurrent ipsilateral DVT, symptomatic thrombophlebitis recurred in 2 of 119 (1.7 percent) patients who were MRDTI negative in the absence of anticoagulant therapy [110,111].
MRV is even less well studied than CTV with only small case series reporting sensitivities >95 percent for the diagnosis of proximal lower extremity DVT [112-116]. In addition, contrast-related complications, high cost, and patient anxiety associated with being in a confined space typically result in avoidance of MRV.
Small prospective studies suggest MRDTI can distinguish new thrombus from old and, therefore, may be a valuable tool for the diagnosis of recurrence [110,117]
●Ascending contrast venography –Ascending contrast venography is performed by injecting iodinated contrast into a dorsal foot vein to outline the entire deep venous system of the lower extremity. An intraluminal defect that is present in more than one view is diagnostic of DVT. It is invasive, expensive, technically difficult to perform (the dorsal vein cannot be cannulated in 5 percent of cases) and interpret (intra-and inter-observer error), and associated with complications including contrast-induced allergic reactions and renal insufficiency [78,118-123].
●Intravascular ultrasonography – This modality is rarely used and reserved mostly for intervention for venous obstruction (See "Overview of iliocaval venous obstruction", section on 'Venography and intravascular ultrasound'.)
DIFFERENTIAL DIAGNOSIS — More than three quarters of patients with DVT, have another cause for their symptoms [118,124]. The following causes of the leg pain were identified in 160 consecutive patients with suspected DVT who had negative venograms [118]:
●Muscle strain, tear, or twisting injury to the leg – 40 percent
●Leg swelling in a paralyzed limb – 9 percent
●Lymphangitis or lymph obstruction – 7 percent
●Venous insufficiency – 7 percent
●Popliteal (Baker's) cyst – 5 percent
●Cellulitis – 3 percent
●Knee abnormality – 2 percent
●Unknown – 26 percent
There are no pathognomic clinical features that reliably distinguish DVT from competing diagnoses since redness, swelling, tenderness and pain are common to many disorders. In addition, DVT may complicate many of these disorders. Thus, patients with these symptoms and signs often have testing to rule out DVT.
Some patients may have findings that suggest specific disorders:
●Calf muscle pull or tear – An inciting injury may be identified in the history, and there may be signs of bleeding on ultrasonography, or bruising at the ankle. (See "Non-Achilles ankle tendinopathy".)
●Cellulitis – Bacterial cellulitis is a common condition of the leg, particularly in patients who have chronic leg swelling due to venous insufficiency or lymphedema. In bacterial cellulitis, the warmth and redness often skip areas and may be associated with constitutional symptoms including fever. Some patients with venous insufficiency develop a low-grade, nonbacterial cellulitis, which resembles infectious cellulitis, but without constitutional symptoms. Although fever increases the suspicion for cellulitis, it can also be present in DVT. (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)
●Superficial thrombophlebitis – Superficial vein thrombophlebitis classically presents with palpable, tender superficial veins. However, since superficial thrombophlebitis is a risk factor for DVT, many of these individuals also undergo ultrasound to rule out DVT. (See "Superficial vein thrombosis and phlebitis of the lower extremity veins".)
●Venous valvular insufficiency – Venous insufficiency is a common cause of chronic unilateral leg edema (picture 1) and may be associated with varicose veins. (See "Diagnostic evaluation of lower extremity chronic venous insufficiency" and "Clinical manifestations of lower extremity chronic venous disease".)
●Lymphedema – Lymphedema is an important cause of chronic, rather than acute edema of the extremities, and a history of pelvic surgery, malignancy, or radiation therapy is often present. (See "Clinical features and diagnosis of peripheral lymphedema".)
●Popliteal (Baker's) cyst – The majority of popliteal cysts are due to either distention of a bursa by fluid originating from a knee joint or posterior herniation of the joint capsule due to increased intra-articular pressure. A popliteal cyst that causes calf symptoms is usually leaking or has ruptured. It is often distinguished from DVT by posterior knee pain, knee stiffness, swelling or a mass behind the knee (especially with the knee in extension), and by bruising around the ankle. However, calf symptoms are common; in addition, compression of the popliteal vein may cause leg swelling or secondary DVT. (See "Popliteal (Baker's) cyst".)
●Inflammatory pathology of the knee – Pain, inflammation, and swelling can accompany any knee joint pathology, which can be confused with a popliteal cyst or DVT. (See "Approach to the adult with unspecified knee pain".)
●Drug-induced edema or heart failure – Leg swelling is a side effect of some drugs, such as calcium channel blockers, and is commonly found in patients with congestive heart failure. The edema is usually bilateral, but can be asymmetric if there is underlying venous pathology; signs of inflammation are not generally present. (See "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis", section on 'Clinical manifestations' and "Approach to diagnosis and evaluation of acute decompensated heart failure in adults", section on 'Clinical manifestations' and "Clinical manifestations and evaluation of edema in adults".)
SPECIAL POPULATIONS — The presentations and diagnosis of DVT in special populations are discussed separately:
●Pregnancy (see "Deep vein thrombosis in pregnancy: Epidemiology, pathogenesis, and diagnosis")
●Phlegmasia cerulea dolens (see "Overview of the treatment of proximal and distal lower extremity deep vein thrombosis (DVT)", section on 'Phlegmasia cerulea dolens')
●Upper extremity DVT (see "Primary (spontaneous) upper extremity deep vein thrombosis")
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Deep vein thrombosis (blood clot in the legs) (The Basics)" and "Patient education: Duplex ultrasound (The Basics)")
●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition – Deep venous thrombosis (DVT) (figure 1) and acute pulmonary embolism (PE) are two manifestations of the same disorder, venous thromboembolism (VTE). Having a high degree of certainty that DVT is "ruled-in" (>85 percent post-test probability of DVT) or "ruled out" (<2 percent post-test probability of progressive VTE in the next three months) is critical so that administering or withholding therapy can be justified. (See 'Introduction' above.)
●Clinical manifestations – DVT of the lower extremity should be suspected in patients who have clinical manifestations with or without risk factors for thrombus (table 1). In general, clinical and laboratory findings have poor sensitivity and specificity diagnostically but may be important when considering alternative diagnoses, or determine how a confirmed DVT will be treated. (See 'Clinical presentation' above.)
●Initial risk stratification – For patients in whom a first DVT is suspected, we suggest a diagnostic approach that incorporates clinical assessment with estimation of pretest probability (PTP) by gestalt and/or the Wells score (calculator 1 and calculator 2) (table 2), D-dimer measurement and, when necessary, compression ultrasonography (CUS) with Doppler of the lower extremities. (see 'Suspected first DVT (risk stratification)' above and 'Assessment of clinical pretest probability' above and 'D-dimer' above):
•Low probability – In patients with a low PTP for DVT, we suggest that a high or moderate sensitivity D-dimer level be performed. Patients in whom the D-dimer level is normal (eg, <500 ng/mL) do not need further testing, while those in whom the D-dimer is positive (eg, ≥500 ng/mL) should have ultrasonography of the lower extremities. Patients can proceed directly to ultrasonography if the D-dimer is expected to be positive due to another condition (table 3). DVT is diagnosed if ultrasonography is positive; no further testing is required if ultrasonography is negative. (See 'Low-probability' above.)
•Moderate probability – In patients with moderate PTP for DVT, we suggest that a high-sensitivity D-dimer level be performed. Patients in whom the D-dimer level is normal do not need further testing, while those in whom the D-dimer is positive should have ultrasonography of the lower extremities. Patients can proceed directly to ultrasonography if the D-dimer is expected to be positive due to another condition (table 3). DVT is diagnosed if ultrasonography is positive. When neither proximal nor distal DVT is identified on whole leg ultrasonography, no further testing is required; in contrast, in those in whom proximal ultrasonography is negative, repeat proximal ultrasonography should be performed at one week to detect extension of distal DVT into the proximal veins. (See 'Moderate-probability' above.)
•High probability – For patients with a high PTP for DVT, we suggest that ultrasonography be performed. DVT is diagnosed if ultrasonography is positive. If DVT is not identified, options include high sensitivity D-dimer level measurement (if not expected to be positive due to another condition), repeat proximal CUS at one week (off anticoagulation), whole leg ultrasonography (if not already performed), or iliac vein ultrasonography (when iliac vein DVT is suspected). Choosing among these options should be individualized. In general, if one or more of these tests are negative in a patient without proximal DVT on ultrasound, then no further testing is required. (See 'High-probability' above.)
●Diagnostic compressive ultrasonography
•Proximal CUS – In most patients with suspected DVT, CUS with Doppler is the imaging test of choice. The presence of DVT is diagnosed by demonstrating non-compressibility of the imaged vein. (See 'Diagnostic ultrasonography suspected first DVT' above and 'Proximal' above.)
•Whole leg CUS – Both proximal and whole leg ultrasonography have a high sensitivity for the detection of thrombus in the proximal veins (ie, common femoral, femoral and popliteal veins). Whole leg ultrasonography additionally examines the veins in the calf (peroneal, posterior and anterior tibial, and muscular veins) and can therefore detect isolated distal DVT. (See 'Whole leg' above.)
•Choosing – Choosing proximal or whole leg ultrasonography varies among experts and is often institution-specific. Thus, it is important that clinicians know which test is performed at their institution and be familiar with the advantages and disadvantages of each test. (See 'Choosing proximal or whole leg ultrasonography' above.)
●Recurrence – For most patients with suspected ipsilateral DVT recurrence, proceeding directly to ultrasonography (proximal or whole leg ultrasonography) OR using an approach similar to that described for first suspected DVT is appropriate. When an ultrasonographic abnormality is identified in patients with suspected recurrence, it may be difficult for the clinician to determine whether it is due to old or new thrombus. Availability of a previous ultrasound or ultrasound report that documents the extent of residual thrombosis greatly improves the accuracy of ultrasound for recurrent DVT. In absence of a previous ultrasound or ultrasound report, MRDTI may be useful. (See 'Suspected recurrent DVT' above.)
●Alternative imaging – For patients with suspected DVT, contrast-enhanced computed tomographic venography (CTV) and magnetic resonance venography (MRV) are rarely used diagnostically, unless there is uncertainty about iliac vein or inferior vena cava thrombosis after ultrasonography. While widely used in the past, ascending contrast venography, which was the gold standard for DVT diagnosis, and impedance plethysmography are now rarely used or available. (See 'Alternative imaging' above.)
●Differential diagnosis – The differential diagnosis in patients with suspected DVT includes muscle strain/tear lymphedema, venous insufficiency, popliteal (Baker's) cyst, and cellulitis. There are no pathognomic clinical features that reliably distinguish DVT from competing diagnoses since redness, swelling, tenderness and pain are common to many of these disorders. (See 'Differential diagnosis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Brydon Grant, MD, who contributed to earlier versions of this topic review.
The UpToDate editorial staff also acknowledges Clive Kearon, MB, MRCP(I), FRCP(C), PhD, now deceased, who contributed to earlier versions of this topic review.