For a patient with DiGeorge syndrome on antipsychotics presenting with acute on chronic lower leg edema and new leg pain, should a D-dimer test be done first or an ultrasound of the lower extremities?

Proceed Directly to Lower Extremity Ultrasound Without D-Dimer Testing

In this 30-year-old female with DiGeorge syndrome on antipsychotics presenting with acute-on-chronic lower leg edema and new leg pain, you should proceed directly to lower extremity ultrasound rather than obtaining a D-dimer first. This patient has multiple factors that make D-dimer testing unreliable and potentially misleading.

Rationale for Skipping D-Dimer

Chronic Edema as a Confounding Factor

• The presence of chronic lower leg edema significantly increases the likelihood of a false-positive D-dimer result, even in the absence of DVT 1
• The American College of Chest Physicians guidelines explicitly state that initial testing with ultrasound is preferred when "the patient has a comorbid condition associated with elevated D-dimer levels and is likely to have a positive D-dimer result, even if DVT is absent" 1

Acute Symptoms Warrant Direct Imaging

• New leg pain superimposed on chronic edema represents a change in clinical status that elevates pretest probability 1
• For patients with moderate-to-high pretest probability, the guidelines recommend proximal compression ultrasound (CUS) or whole-leg ultrasound as acceptable initial tests 1

Clinical Assessment of Pretest Probability

This Patient Likely Has Moderate-to-High Pretest Probability

• Acute symptom onset (new leg pain) in the setting of chronic edema suggests moderate pretest probability at minimum 1
• Antipsychotic medications can contribute to venous stasis through sedation and reduced mobility 2
• The combination of baseline chronic edema plus acute pain makes low pretest probability unlikely 1

When Pretest Probability is NOT Low

• For moderate pretest probability: both highly sensitive D-dimer and proximal CUS are acceptable initial tests, but ultrasound is preferred when comorbid conditions make D-dimer elevation likely 1
• For high pretest probability: ultrasound (proximal CUS or whole-leg US) is recommended over D-dimer testing 1

Practical Considerations

Efficiency and Diagnostic Certainty

• A positive D-dimer in this patient would necessitate ultrasound anyway, making the D-dimer an unnecessary intermediate step 1
• A negative D-dimer might provide false reassurance given the chronic edema and could delay definitive diagnosis 1

DiGeorge Syndrome Considerations

• While DiGeorge syndrome itself is not specifically associated with hypercoagulability, patients may have cardiac anomalies that could contribute to venous stasis 3, 4, 5
• The psychiatric manifestations of DiGeorge syndrome may necessitate antipsychotic treatment, which can reduce mobility and increase DVT risk 4, 6, 2

Recommended Diagnostic Approach

Proceed directly to lower extremity duplex ultrasound with the following specifications:

• Order proximal compression ultrasound (CUS) as the initial test 1
• If proximal CUS is negative and clinical suspicion remains high due to the acute symptoms, consider whole-leg ultrasound to evaluate for isolated calf DVT 1
• Whole-leg ultrasound may be particularly appropriate given the severe symptoms (new pain) and the patient's ability to follow up may be uncertain 1

Common Pitfalls to Avoid

• Do not rely on D-dimer in patients with chronic edema - the false-positive rate makes it clinically unhelpful 1
• Do not assume low pretest probability when acute symptoms develop in chronic conditions - the change in clinical status elevates risk 1
• Do not delay imaging while waiting for D-dimer results - this wastes time and may worsen outcomes if DVT is present 1