NP Reasoning

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Acute Leg Swelling

Victoria Sanderson

Use of Wells’ Criteria, D-dimer, and Ultrasound for DVT

Case: a 60-year-old female presents with acute left leg swelling and pain.

What is your differential for acute unilateral leg swelling and pain before assessing the patient?

I like to use the system’s diagnostic framework to think about 4 major buckets: Vascular, MSK, Dermatologic, and Lymphatic.

BOTTOM LINE: Use a diagnostic framework to guide your differential before evaluating the patient. E.g. you can think of the vascular, musculoskeletal, dermatologic, and lymphatic systems.

Back to the case: She has left leg swelling and erythema medially below the knee, with warmth and tenderness along a palpable cord. There is tenderness along the deep venous system. She denies any recent trauma or shortness of breath. She has a history of chronic venous insufficiency but is otherwise healthy. You know that deep venous thrombosis (DVT) is a must-not-miss diagnosis for this presentation. It is recommended that we use a validated clinical decision tool to estimate our pre-test probability for DVT (8).

What is Wells’ Criteria for DVT?

The Wells’ Criteria for DVT can be used in the outpatient and emergency department setting to risk stratify patients for DVT (9). It helps us determine the need for more testing to rule out DVT (e.g. D-dimer +/- ultrasound).

For a DVT diagnosis, both a 3-level pre-test probability (low, intermediate, high) and 2-level (likely vs. unlikely) have been validated (8).

It incorporates clinical gestalt with a minus 2 score for “alternative diagnosis more likely” – this is a hard one to answer if you haven’t seen many acute lower limb presentations!

When there is clinical suspicion for DVT, we should always assess for pulmonary embolism.

How do we Interpret Wells’ Criteria scores?

A score of 0: DVT low probability, with a prevalence of ~5% (i.e. no further testing needed) (9). Consider other differential diagnoses.

A score of 1-2: DVT intermediate probability (prevalence of ~17%) - not reassuring enough to send your patient home! These patients should proceed to high-sensitivity D-dimer testing, and if positive, proceed to ultrasound (9). If D-dimer is negative, this is sufficient to rule out DVT with a post-test probability of <1% (9).

A score of >2: DVT high probability (prevalence of 17-53%) (9). All patients should receive ultrasound. D-dimer testing can be utilized to help risk-stratify patients if the ultrasound is negative.

Back to the case: with a score of 2 (intermediate pre-test probability) you proceed with high-sensitivity D-dimer testing.

Diagnostic Testing for DVT: D-dimer & Ultrasound

D-DIMER PEARLS

  • High-sensitivity D-dimer is needed over moderate-sensitivity D-dimer to risk stratify patients (8, 9). D-dimer used in Canada is typically >90% sensitive (8).

  • D-dimer is sensitive (good at ruling out DVT, low risk of a false negative result) but not specific (bad at ruling in DVT, risk of a false positive result) – because it can be elevated with many conditions including: malignancy, pregnancy, surgery, hospitalization, trauma, inflammatory diseases, advanced age (8). Meaning, if you have a positive D-dimer for a patient with intermediate or high pre-test probability for DVT, they will need further testing (ultrasound).

How do we Interpret D-dimer Results?

No standard validated D-dimer cut off exists, however different cut-offs have been suggested based on clinical probability and age (10).

Clinical probability cut-off suggestions: A d-dimer level cut-off of <1000ng/mL can be used to exclude DVT in patients with low pre-test probability (10), with 99% negative predictive value (11). A D-dimer cut off of <500ng/mL can be used to exclude DVT in patients with intermediate pre-test probability (Wells Score 1-2) (10), with 99.6% negative predictive value (11).

Age cut-off suggestions:

  • <50 years old: cut off of <500ng/mL (value considered normal).

  • >50 years old: Value is normal if the D-dimer result is LESS THAN patients age x 10 (e.g. age 70 x 10 = 700 and D-dimer result is 600, this would be considered a negative result).

BOTTOM LINE: If your pre-test probability for DVT is low, a D-dimer of <1000ng/mL reasonably rules it out. If your pre-test probability for DVT is intermediate, a D-dimer of <500ng/mL reasonably rules it out. Consider age as well. If your pre-test probability is high, D-dimer is not enough to rule out DVT!

Ultrasound for DVT

Complete duplex ultrasound is the preferred venous ultrasound protocol for diagnosing acute DVT, which involves compression of the deep veins from the inguinal ligament to the ankle and doppler waveforms in the common femoral and popliteal vein (12). Ultrasound has a sensitivity of 94% and 97.3% respectively for DVT (12).

Pearl for clinically diagnosed superficial venous thrombosis: ultrasound should be performed in the majority of patients, especially if symptoms are above the knee or located close to the popliteal fossa, in those with symptoms suggestive of DVT, or with venous thrombosis risk factors (2). Patients with superficial venous thrombosis below the knee restricted to a varicose vein without additional venous thrombosis risk factors may not require ultrasound assessment (2).

Should I order D-Dimer or Ultrasound or Both? It depends on your pre-test probability!

Let’s consider these scenarios:

1) Wells score of 1-2 or low pre-test probability: a high sensitivity D-dimer can be ordered first. If the dimer is negative, it can be helpful to rule out DVT in these lower risk patients. If the D-dimer is positive there is little diagnostic value, and an ultrasound needs to be ordered to assess for DVT (8,9). If the ultrasound is positive, strongly consider treatment (9).

2) Wells score of >2 or moderate-high pre-test probability: ultrasound can be ordered first. If the ultrasound is positive, we strongly consider treatment. If the ultrasound is negative, D-dimer testing can help further risk stratify the patient. If the D-dimer is positive, this is still concerning for DVT, so repeat ultrasound in 5-7 days is indicated (8,9). If the D-dimer is negative, repeat ultrasound may not be required.

BOTTOM LINE: Start with your Wells score to estimate your pre-test probability of DVT.

If you have a Wells’ score of 1-2 (intermediate pre-test probability), order a D-dimer. Use a combination of pre-test probability and age adjustment to interpret the results.

If you have a Wells’ score of >2 (high pre-test probability), order an ultrasound first.

Summary of Interpreting Results of D-Dimer and Ultrasound for DVT

Back to the case: D-dimer is 2000ng/mL (positive), so a venous duplex ultrasound is ordered, which confirms the presence of a DVT. Positive ultrasound + positive D-dimer = strongly consider treatment.

BOTTOM LINE:

Intermediate or “unlikely” pre-test probability using Wells criteria (1-2):

Order D-dimer first. If negative, likely ruled out DVT. If positive, order ultrasound.

High or “likely” pre-test probability using Wells criteria (>2):

Order ultrasound first. If positive, treat for DVT. If negative, order D-dimer to further risk stratify. If D-dimer is positive, repeat US in 5-7 days. If negative, DVT likely ruled out.

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References 
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  9. MDCalc. Wells Criteria for DVT [Internet]. MDCalc; [cited 2025 Jan 12]. Available from: https://www.mdcalc.com/calc/362/wells-criteria-dvt#pearls-pitfalls
  10. BC Ministry of Health. Appendix B: D-dimer cut-off values [Internet]. Victoria (BC): BC Guidelines; [cited 2025 Jan 12]. Available from: https://www2.gov.bc.ca/assets/gov/health/practitioner-pro/bc-guidelines/appendix_b_-_d-dimer_cut-off_values.pdf
  11. Thomas MR, Robinson SL, Busfield R, Williams J, Collins GS, Wright BJ. Characteristics and outcomes of patients with low risk pulmonary embolism defined by the simplified Pulmonary Embolism Severity Index (sPESI): a retrospective cohort study [Internet]. BMJ. 2022;376:e067378 [cited 2025 Jan 12]. Available from: https://www.bmj.com/content/376/bmj-2021-067378
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