What are the initial investigations for a young patient presenting with Paget-Schroetter disorder and suspected thrombophilia, including both acquired and hereditary causes?

Investigations for Paget-Schroetter Syndrome with Suspected Thrombophilia

For a young patient presenting with Paget-Schroetter syndrome (effort thrombosis), a comprehensive thrombophilia workup should include both initial diagnostic tests for the venous thrombosis and specific investigations for acquired and hereditary thrombophilia factors.

Initial Diagnostic Evaluation

1. Imaging Studies:

   • Doppler ultrasound of the affected upper extremity (first-line)
   • Venography if diagnosis remains uncertain or to characterize anatomy prior to treatment

2. Basic Coagulation Tests:

   • Complete blood count (CBC)
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (aPTT)

Thrombophilia Workup

Hereditary Thrombophilia Testing:

1. Genetic Testing:

   • Factor V Leiden (R506Q) mutation
   • Prothrombin gene (G20210A) mutation

2. Natural Anticoagulant Deficiencies:

   • Antithrombin level (functional and antigen)
   • Protein C level (functional and antigen)
   • Protein S level (free and total)

Acquired Thrombophilia Testing:

1. Antiphospholipid Syndrome:

   • Lupus anticoagulant (combination of clot-based assays)
   • Anti-cardiolipin antibodies (IgG and IgM)
   • Anti-β2-glycoprotein-I antibodies (IgG and IgM)
   • Note: If positive, testing should be repeated after 12 weeks to confirm diagnosis 1

2. Myeloproliferative Neoplasms:

   • JAK2V617F mutation
   • If JAK2V617F negative, test for calreticulin mutation
   • Consider bone marrow histology if both are negative 1

3. Other Acquired Conditions:

   • Paroxysmal nocturnal hemoglobinuria (PNH) screening
   • Autoimmune disorder screening

Important Considerations

• Timing of Testing: Perform thrombophilia testing before initiating anticoagulation when possible, or after completion of anticoagulation therapy (minimum 2 weeks after discontinuation) to avoid false results

• Repeat Testing: The diagnosis of hereditary deficiencies should not be made based on a single abnormal test result. Repetitive testing when the patient is not on anticoagulant therapy is mandatory to confirm the diagnosis 2

• Pre-analytical Variables: Consider factors that may affect results including:

  • Acute thrombotic event (can decrease natural anticoagulant levels)
  • Liver function
  • Hormonal status
  • Pregnancy
  • Inflammatory conditions 2

Special Considerations for Paget-Schroetter Syndrome

Since Paget-Schroetter syndrome is primarily related to anatomical abnormalities and repetitive trauma at the thoracic outlet 3, 4, additional investigations should include:

• Assessment of thoracic outlet anatomy (MRI or CT)
• Evaluation for costoclavicular compression
• Examination for first rib anomalies

Management Implications

The identification of underlying thrombophilia in a patient with Paget-Schroetter syndrome has important implications for:

1. Duration of anticoagulation therapy
2. Need for surgical decompression
3. Risk of recurrence
4. Family screening considerations

The comprehensive thrombophilia workup is essential for determining the optimal management strategy and long-term anticoagulation needs in young patients with Paget-Schroetter syndrome. 1