Management of Unilateral Leg Pain with Elevated D-dimer

Diagnostic Algorithm

Perform proximal compression ultrasound (CUS) evaluating the femoral and popliteal veins as the definitive next diagnostic test, as recommended by the American College of Chest Physicians, for patients with a D-dimer of 9.0 mg/L 1, 2, 3
The American College of Chest Physicians guidelines clearly state that when D-dimer is positive, further testing with CUS of the proximal veins is recommended rather than whole-leg ultrasound or venography, for patients with suspected deep vein thrombosis (DVT) 1, 2

Treat immediately for DVT with anticoagulation without performing confirmatory venography, if proximal CUS is positive, as recommended by the American College of Chest Physicians with a Grade 1B recommendation 1, 3, 4
Repeat proximal CUS in 1 week to detect propagating distal thrombus, if initial proximal CUS is negative, especially given the extremely high D-dimer level 3, 5

If there is extensive unexplained leg swelling with negative proximal CUS, image the iliac veins with CT venography or MR venography to exclude isolated iliac DVT, as recommended by the American College of Chest Physicians 1, 6, 7
Evaluate for pulmonary embolism (PE) symptoms, such as dyspnea, chest pain, or syncope, as PE can occur with or without detectable lower extremity DVT, and proceed with PE evaluation including CT pulmonary angiography if symptoms are present 7

The American College of Chest Physicians notes that D-dimer has limited utility in hospitalized patients due to high false-positive rates from comorbid conditions, but once D-dimer is already elevated, the diagnostic algorithm proceeds with imaging regardless of inpatient versus outpatient status 1, 2, 3, 6