What labs should be ordered for a patient with a first-degree relative with Deep Vein Thrombosis (DVT)?

Laboratory Testing for Patients with First-Degree Relatives with DVT

For patients with a first-degree relative with DVT, thrombophilia testing should be considered, particularly focusing on Factor V Leiden and Prothrombin G20210A mutations, which are the most common heritable thrombophilic risk factors. 1

Rationale for Testing

The presence of a first-degree relative with DVT raises concern for potential inherited thrombophilia, which can significantly increase a person's lifetime risk of venous thromboembolism (VTE). The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) guidelines highlight that:

• Factor V Leiden (FVL) is present in 15-20% of individuals with an initial VTE episode 1
• Prothrombin G20210A mutation is the second most common heritable risk factor for VTE 1
• First-degree relatives of patients with FVL have a 2.1-fold increased relative risk of DVT compared to non-carriers 1

Recommended Laboratory Tests

1. Factor V Leiden (R506Q) mutation

   • Most common heritable thrombophilic risk factor 1
   • Present in 15-20% of individuals with initial VTE 1
   • Heterozygosity increases VTE risk 4-7 fold; homozygosity increases risk 9-80 fold 1

2. Prothrombin G20210A mutation

   • Second most common heritable risk factor 1
   • Present in 6% of individuals with initial VTE 1
   • Increases VTE risk by 2-4 fold 1

3. Natural anticoagulant deficiencies

   • Antithrombin deficiency
   • Protein C deficiency
   • Protein S deficiency
   • These deficiencies taken together significantly increase risk of VTE 2

4. Antiphospholipid antibody panel

   • Lupus anticoagulant
   • Anticardiolipin antibodies
   • These can identify acquired thrombophilia 3

5. Homocysteine levels

   • Hyperhomocysteinemia is associated with increased thrombotic risk 3, 2

Testing Approach

The American College of Chest Physicians recommends a structured approach to testing based on clinical context:

1. Initial assessment: Use validated clinical prediction rules like the Wells score to stratify patients into probability categories 4

2. Testing sequence:

   • Begin with Factor V Leiden and Prothrombin G20210A mutation testing as these are most common 1
   • Include testing for natural anticoagulant deficiencies (antithrombin, protein C, protein S) 3
   • Consider antiphospholipid antibody testing and homocysteine levels 3

Important Considerations and Pitfalls

• Timing of testing: Ideally perform testing when the patient is not on anticoagulation therapy, as this can affect results of functional assays (protein C, protein S, antithrombin) 3

• Comprehensive approach: Testing for only one or two abnormalities may miss significant thrombophilia. Studies show that 11% of patients may have more than one thrombophilic defect 5

• Clinical relevance: The presence of thrombophilia markers may influence decisions about:

  • Duration of anticoagulation therapy
  • Prophylaxis during high-risk situations
  • Family screening 5

• Avoid testing during acute thrombosis: Acute thrombosis and anticoagulation can affect test results, particularly for functional assays 3

• Consider family testing: If a hereditary thrombophilia is identified, testing of asymptomatic family members may be warranted to identify those at increased risk 1

By following this structured approach to laboratory testing for patients with first-degree relatives with DVT, clinicians can identify those with inherited thrombophilia who may benefit from tailored management strategies to prevent future thrombotic events.