To provide an evidence-based approach to the evaluation of patients with suspected deep vein thrombosis (DVT).An estimated 45,000 patients in Canada are affected by DVT each year, with an incidence of approximately 1-2 cases per 1,000 persons annually. This translates into 2-4 DVTs per year in a typical, solo Canadian family practice. Since only 10-20% of patients with suspected DVT actually have the disease, a typical family practice will evaluate 20-40 patients with symptoms and/or signs suggestive of DVT each year. The ability to rapidly and accurately assess patients for DVT is crucial. A validated diagnostic algorithm should be used in the evaluation of patients with suspected DVT. Treatment of DVT once diagnosed prevents thrombus extension and pulmonary embolism (PE) and initiation of anticoagulation should be considered prior to confirmation of DVT while awaiting diagnostic tests, unless contraindications exist . The accurate exclusion of DVT eliminates unnecessary exposure to long term anticoagulants, which has treatment burdens and bleeding risks.# DIAGNOSIS:
The diagnosis of DVT is based on:

# 1) Pre-test probability (clinical suspicion)
It is recommended that a validated clinical decision rule be used to characterize pre-test probability of DVT. There are several formal models available, of these, the Wells Score is the most widely used (see Table 1). For DVT diagnosis, both a three-level (low, intermediate, high pre-test probability) and two-level (unlikely, likely) Wells score have been prospectively validated. The two-level score is displayed in the table and diagnostic algorithm below. 

# CLINICAL FINDINGS POINTS
Paralysis, paresis or recent orthopedic casting of lower extremity 1
Bedridden >3 days recently or major surgery within past 12 weeks 1
Localized tenderness of the deep veins 1
Swelling of entire leg 1
Calf swelling 3 cm greater than other leg (measured 10 cm below the tibial tuberosity)
Pitting edema greater in the symptomatic leg 1

# Non-varicose collateral superficial veins 1
Active cancer or cancer treated within 6 months 1 

# 3) D-Dimer
D-Dimer is a sensitive but non-specific marker of thrombosis. Although D-dimer is elevated in patients with DVT, it is also elevated in a variety of other common conditions including, but not limited to, inflammatory diseases, malignancy, pregnancy, surgery, hospitalization, trauma, and advanced age. This renders the test useful to help rule out DVT when negative but of little diagnostic value when positive. Although there are several D-dimer assays available, those that are typically used in Canada are all highly sensitive assays (sensitivity of greater than 90%) and can be used in combination with an unlikely pre-test probability to exclude DVT. However, clinicians should check with their laboratory to confirm the sensitivity of the D-dimer assay used locally.
There is good evidence for the use of a fixed, standard D-dimer cutoff with validated clinical prediction rules to exclude DVT. The use of a three level Well's score pre-test probability specific D-dimer cutoff was evaluated in one randomized trial that showed this strategy to be as safe as using a fixed cutoff. A second prospective management study has been completed, and preliminary results similarly show it to be a safe strategy for ruling out DVT while reducing the need for CUS. The role of a pre-test probability specific D-dimer cut-off with the two level Well's score has not been investigated. The use of an age-adjusted Ddimer cutoff has not been well validated for excluding DVT (unlike for PE). As such, its use for DVT diagnosis is not routinely recommended at this time.
Community-based physicians are often unlikely to receive timely D-dimer results from outside laboratories and may not be able to use strategies involving sequential tests. Alternative management approaches include diagnostic algorithms incorporating pre-test probability assessment and CUS (outlined below). In some centres, the option of referring patients to a Thrombosis Clinic may be available to facilitate rapid assessment.

# DIAGNOSTIC STRATEGY:
Patients with suspected DVT should first undergo a history and physical exam focused on the components of the Wells Score, as well as symptoms and signs of PE .
- Patients with an unlikely pre-test probability for DVT should then undergo D-dimer testing with management as outlined in Figure 1 below. - Patients with a likely pre-test probability should have proximal CUS as the recommended first-line test. Those with a negative proximal CUS should undergo Ddimer testing (to determine the need for repeat CUS) or repeat CUS in 5-7 days to exclude the possibility of distal DVT that has extended proximally.
In jurisdictions where proximal CUS is readily available in a timely manner and where D-dimer turnaround times are long, proceeding directly to proximal CUS for all patients suspected of a DVT is a reasonable but more costly strategy. With this approach, a negative proximal CUS and unlikely pre-test probability excludes DVT, while patients with a likely pre-test probability and negative proximal CUS should have CUS repeated in 5-7 days.
If whole leg CUS is undertaken and isolated distal DVT is detected, anticoagulation can be offered if severe symptoms are present or if the risk of proximal extension is high . Alternatively, patients may be followed with serial CUS over a 1-2 week period, after which time thrombus extension is unlikely. Those unlikely or unable to return for follow-up testing should generally be treated. Risk factors for proximal extension of a distal DVT include: positive D-dimer, calf DVT that is extensive or close to the proximal veins, absence of a reversible provoking risk factor, cancer, previous history of venous thromboembolism, lower extremity immobilization (e.g. plaster casting, neuromuscular disease), and in-patient status.
Figure 1. Suggested diagnostic strategy for patients with suspected DVT. *Clinical probability can be assessed by clinical decision rule, such as two-level Wells score. D-dimer should be measured using a highly sensitive assay to rule out DVT using this algorithm; if D-dimer testing is not available, CUS should be performed in all patients; a negative CUS and unlikely pre-test probability excludes DVT, while patients with a likely pre-test probability and negative CUS should have CUS repeated in 5-7 days. pCUS, proximal compression ultrasound.

# SPECIAL CONSIDERATIONS:

# Timing of diagnostic testing:
Testing should be undertaken as quickly as possible. However, if there will be a significant delay (greater than 4 hours), patients with a moderate/high or likely pre-test probability of DVT should receive a rapidly acting anticoagulant (e.g. low-molecular-weight heparin or a direct oral anticoagulant) until testing is performed, unless they are at high risk of bleeding or have another contraindication to anticoagulant therapy.

# Suspected recurrent DVT:
In the case of suspected recurrent ipsilateral DVT, CUS can be problematic because residual compression abnormalities are often present from the previous DVT. In such cases, it is important to compare CUS results with those from prior examinations. Recurrent DVT can only be definitively diagnosed with evidence of new thrombosis, including non-compressibility in previously normal venous segments or increases of at least 4 mm in compression diameter from prior studies. A negative D-dimer may make the diagnosis of recurrence less likely and may be helpful when no prior CUS studies are available for comparison. Consultation with an expert in the field may be helpful in this setting and especially when no prior CUS is available for comparison.

# Upper extremity DVT (UEDVT):
UEDVT is uncommon with an annual incidence of approximately 3/100,000 persons. Most patients with UEDVT have risk factors including central venous catheter, recent pacemaker or malignancy. Spontaneous UEDVT is often related to sudden physical effort and narrowing of the thoracic outlet (Paget-Schroetter syndrome, thoracic outlet syndrome). Clinical manifestations include acute and chronic arm pain, swelling, discoloration, and dilated collateral veins over the arm, neck or upper chest.
Pre-test probability for UEDVT is typically determined by clinical gestalt. The Constans Decision Score (which includes central venous catheter or pacemaker, localized pain, or unilateral edema) has also been shown to safely exclude UEDVT when used in combination with highsensitivity D-dimer. However, this approach has had only limited validation in one prospective management study. In general, combined CUS and color Doppler flow studies (duplex ultrasound) generally are used to evaluate patients with suspected UEDVT:
- In patients with low/unlikely pre-test probability, a strategy starting with D-dimer is suggested, followed by duplex ultrasound if D-dimer is positive. If D-dimer is not readily available, performing duplex ultrasound alone is acceptable.
- In patients with high/likely pre-test probability, duplex ultrasound should be performed to exclude UEDVT. If the initial US is negative, the diagnosis can be considered excluded unless the clinical suspicion remains high. In that case, further testing with D-dimer (with additional imaging if positive), repeat ultrasound, or traditional contrast venography, CT venography, or MRI is suggested.

# Pediatrics:
The incidence of DVT in children is lower than adults (0.7 to 0.14 per 10,000 children) and when it does occur it is more often associated with or use of central venous catheters, a primary disease (such as cancer and congenital heart disease), after intervention. The use of clinical decision rules and D-dimer testing has not been validated in children. Diagnosis of DVT is initiated with a CUS. While CUS testing is non-invasive, it may not be accurate for the upper extremity venous system and there have been few studies in the lower venous system. If the clinical suspicion is high for DVT with a negative CUS, the use of magnetic resonance imaging or computed tomography may be considered.

# Suspected DVT in pregnancy:
See Clinical Guide Pregnancy: Diagnosis of DVT and PE.
OTHER RELEVANT THROMBOSIS CANADA CLINICAL GUIDES:
- Central Venous Catheter-Related Venous Thrombosis 

# Date of Version: 20July2021
Please note that the information contained herein is not to be interpreted as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about any medical matter, you should consult your doctor or other professional healthcare providers, and as such you should never delay seeking medical advice, disregard medical advice or discontinue medical treatment because of the information contained herein.