Recommended Thrombophilia Testing for a 55-Year-Old Male with Strong Family History of Blood Clots
For a 55-year-old male with a strong family history of blood clots, testing should include Factor V Leiden, Prothrombin 20210A, and functional coagulation assays for antithrombin III, protein C, and protein S, along with plasma homocysteine measurement. 1
Initial Laboratory Evaluation
- Complete blood count (CBC), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be ordered as basic screening tests 1
- Factor V Leiden (R506Q) mutation testing is indicated as the primary genetic test for inherited thrombophilia 1
- Prothrombin 20210A variant testing should be performed simultaneously with Factor V Leiden testing, as it is the second most common inherited thrombophilia 1
- Plasma homocysteine level measurement is recommended rather than MTHFR genetic testing, as hyperhomocysteinemia interacts synergistically with Factor V Leiden 1
- Functional coagulation assays for antithrombin III, protein C, and protein S deficiencies should be included in the panel 1
Rationale for Testing Selection
- Factor V Leiden and Prothrombin 20210A mutations are the most common inherited thrombophilias and are easily detected through DNA testing 1, 2
- Venous thrombosis is multifactorial, and the presence of more than one genetic risk factor is not uncommon, justifying panel testing 1
- A strong family history of venous thrombosis increases the likelihood of identifying heritable thrombophilic defects, though the correlation is not perfect 1, 3
- Protein S, protein C, and antithrombin III deficiencies are too genetically heterogeneous for routine molecular genetic testing but can be assessed through functional assays 1
Testing Considerations and Limitations
- Testing should ideally be performed when the patient is not on anticoagulant therapy, as these medications can affect test results 2
- Repetitive testing may be necessary to confirm diagnoses, particularly for protein C, protein S, and antithrombin III deficiencies 2
- Pre-analytical errors and acquired causes of low levels of natural coagulation inhibitors are more common than hereditary deficiencies 2
- Family history alone is not a precise tool to identify patients with inherited thrombophilia, with a positive family history having a likelihood ratio of only 1.3 for identifying an inherited thrombophilia 3
Additional Testing to Consider
- Lupus anticoagulant and anticardiolipin antibodies should be considered to rule out antiphospholipid syndrome, an acquired thrombophilia 2
- D-dimer testing may be useful for risk stratification in patients with previous thrombotic events 1
- Residual vein occlusion detected by venous ultrasound does not predict recurrence risk to a clinically useful degree 1
Common Pitfalls to Avoid
- Testing for the Factor V R2 allele (H1299R) is not currently indicated in routine thrombophilia workup 1
- Testing for MTHFR gene variants is less informative than direct measurement of plasma homocysteine levels 1
- Relying solely on family history to determine testing strategy may miss important thrombophilic factors 3
- Failing to repeat abnormal test results for confirmation can lead to misdiagnosis 2
By following this comprehensive testing approach, clinicians can identify inherited thrombophilias in patients with a family history of blood clots, allowing for appropriate risk stratification and management decisions.