What additional lab work is recommended for a patient with bilateral leg swelling, pain, elevated C-Reactive Protein (CRP) and mildly elevated D-Dimer, following negative unilateral ultrasound and lumbar X-ray?

Additional Laboratory Work for Bilateral Leg Swelling with Elevated CRP and Mildly Elevated D-Dimer

Given the bilateral presentation with negative unilateral ultrasound, you need to order a complete blood count, comprehensive metabolic panel, coagulation profile (PT/INR, aPTT), and proceed directly to bilateral whole-leg ultrasound with iliac vein imaging rather than relying on additional lab work alone. 1, 2

Critical Imaging Gap to Address First

Your patient has had only a unilateral ultrasound, but presents with bilateral leg swelling. This is a fundamental mismatch that must be corrected before pursuing additional laboratory testing:

• Order bilateral whole-leg venous ultrasound immediately, as the American College of Chest Physicians recommends whole-leg ultrasound over proximal compression alone in patients with severe symptoms or extensive swelling 3, 2
• If bilateral ultrasound is negative but swelling persists, proceed to CT or MR venography of iliac veins to evaluate for isolated iliac DVT, which standard proximal ultrasound misses and presents with extensive leg swelling 3, 2
• The extensive bilateral swelling places this patient in a higher pretest probability category where isolated iliac vein thrombosis must be excluded 2

Essential Laboratory Testing

While imaging takes priority, obtain these labs concurrently:

• Complete blood count to establish baseline values and identify potential contraindications to anticoagulation if DVT is diagnosed 1
• Comprehensive metabolic panel to assess kidney and liver function, which will influence anticoagulant selection and dosing if treatment is needed 1
• Coagulation profile including PT/INR and aPTT to guide potential anticoagulant therapy 1

Why Additional D-Dimer Testing Is Not Helpful

• Do not repeat D-dimer testing, as a positive D-dimer following negative initial ultrasound requires additional imaging rather than clinical observation alone 2
• In patients with high pretest probability (which your patient has given bilateral swelling and pain), D-dimer should not be used as a stand-alone test to rule out DVT 3, 2
• The American Society of Hematology explicitly recommends against using a positive D-dimer alone to diagnose DVT 3

Alternative Diagnostic Considerations After DVT Exclusion

If comprehensive bilateral imaging excludes DVT, consider these diagnoses that explain bilateral swelling with elevated inflammatory markers:

• Right heart failure, which causes bilateral lower extremity edema with elevated inflammatory markers 2
• Chronic venous insufficiency, particularly relevant given bilateral presentation 2
• May-Thurner syndrome, specifically evaluated with iliac vein imaging, more common on left but can cause bilateral symptoms 2

Critical Pitfalls to Avoid

• Do not overlook iliac vein pathology, as standard proximal ultrasound misses isolated iliac DVT, which presents with extensive leg swelling 3, 2
• Do not rely on D-dimer alone in high-probability patients, as the extensive bilateral swelling places this patient in a higher pretest probability category 3, 2
• Failing to image both legs when symptoms are bilateral is a fundamental error that leaves half the clinical picture unexamined 2

Pulmonary Embolism Consideration

Given the elevated D-dimer and clinical context:

• Assess for symptoms of pulmonary embolism including syncope, chest pain, or dyspnea, as PE can occur despite negative lower extremity ultrasound 1
• If PE symptoms are present, perform CT pulmonary angiography, as syncope with prior leg swelling raises concern for possible PE despite negative DVT imaging 1