What laboratory tests are ordered for a patient presenting with swelling of the legs?

Laboratory Workup for Leg Swelling

Order a D-dimer test and comprehensive metabolic panel as your initial laboratory evaluation, with additional testing guided by clinical presentation and pretest probability for deep vein thrombosis. 1, 2

Initial Laboratory Tests

Core Laboratory Panel

• Comprehensive metabolic panel to assess kidney function (creatinine, BUN), liver function (albumin, transaminases), and electrolytes 1, 3
• Complete blood count with platelet count to identify anemia, infection, or hematologic disorders 4, 3
• Urinalysis with protein-to-creatinine ratio (PCR) - PCR >300-350 mg/mmol indicates nephrotic range proteinuria, which can cause edema 5
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism as a systemic cause 3, 2
• Brain natriuretic peptide (BNP) if heart failure is suspected based on clinical presentation 2

DVT-Specific Testing Algorithm

For unilateral leg swelling or moderate-to-high DVT probability:

• Proceed directly to compression ultrasound (CUS) without D-dimer testing 6, 7
• If proximal CUS is positive, initiate treatment immediately without confirmatory testing 6, 7

For low pretest probability or bilateral swelling:

• D-dimer testing should be performed first 1, 7
• If D-dimer is negative and single proximal CUS is negative, no further testing is needed 6, 7
• If D-dimer is positive, proceed to compression ultrasound or whole-leg ultrasound 1, 7

Additional Testing Based on Clinical Context

For Suspected Venous Insufficiency (Chronic Bilateral Edema)

• Duplex ultrasonography with reflux to diagnose chronic venous insufficiency 2
• This is the most common cause in older adults and requires imaging rather than laboratory confirmation 3

For Suspected Systemic Causes

• Liver function tests including albumin and total protein if cirrhosis or hypoalbuminemia suspected 3, 2
• HbA1c for diabetic patients to assess glycemic control 1
• Coagulation profile (PT/INR, aPTT) if anticoagulation is being considered 4

For Suspected Secondary Causes

• Autoimmune markers (ANA, ANCA, antiphospholipid antibodies) if autoimmune disease suspected 8
• Lipid panel if nephrotic syndrome is being considered (associated with hyperlipidemia) 5

Common Pitfalls to Avoid

• Do not use D-dimer as a standalone test in high pretest probability DVT - proceed directly to imaging 6
• Do not delay imaging for laboratory results when acute unilateral swelling suggests DVT 7, 2
• Do not forget to image iliac veins in patients with extensive unexplained leg swelling when proximal CUS is negative 6, 7
• Do not order D-dimer after DVT is already established - it has no role in monitoring treatment 4
• Do not overlook medication-induced edema - review antihypertensives, NSAIDs, and hormones before extensive workup 2

Special Populations

Pregnant Patients

• Initial evaluation with proximal CUS, followed by serial CUS or D-dimer if initial CUS is negative 7

Patients with Diabetes

• Include ankle-brachial index (ABI) testing if symptoms of claudication or absent pedal pulses are present 1
• Perform neurological assessment with 10-g monofilament for peripheral neuropathy 1

Patients Unable to Return for Follow-up

• Consider whole-leg ultrasound instead of proximal CUS to avoid need for serial testing 6, 7