1. Home>
2. Specialties>
3. Oncology and Hematology>
4. Summary and Comment

Screening for Thrombophilia

Study results suggest that immediate relatives of patients with specific thrombophilic defects be considered for testing.

When a patient presents with an idiopathic venous thrombosis (VT; a thrombus not associated with surgery, trauma, or malignancy), the clinician must answer two questions: Should the patient (proband) be tested for thrombophilia to determine the underlying cause of VT? And, if a thrombophilic defect is found, should the proband’s family members be tested? Most clinicians would order testing of the proband, but the decision to test family members would depend on their perceived risk for VT.

To provide an evidence-based approach to determining suitability of family testing, investigators in the Netherlands performed a retrospective study of 2479 family members of 877 probands to assess absolute risks for first and recurrent VT among these relatives and to associate such risks with the relatives’ known thrombophilic defects. Such defects included deficiencies of antithrombin and proteins C and S (ACS); presence of factor V Leiden (FVL) and prothrombin G20210A (ProGA); high levels of factor (F) VIII, FIX, FXI, and thrombin activatable fibrinolysis inhibitor (TAFI); and hyperhomocysteinemia.

During a median observation period of 30 years, VT occurred in 229 (9%) of relatives. The prevalence of VT in relatives with ACS deficiencies was higher than in those with FVL, ProGA, or high FVIII levels (21% vs. 8%; P<0.001); those with ACS deficiencies also had VT (either idiopathic or provoked) at earlier ages (29 vs. 40 years; P<0.001). Relatives with high FIX, FXI, or TAFI levels or hyperhomocysteinemia had excess risk for VT only if they also had high FVIII levels. Relatives with more than one thrombophilic defect also had excess risk, especially if one of the defects was ACS deficiency. Cumulative recurrence rates after cessation of anticoagulant therapy were higher in relatives with ACS deficiencies than in those with FVL, ProGA, or high FVIII levels after 2 years (19% vs. 7%), 5 years (40% vs. 11%), and 10 years (55% vs. 25%).

Comment: These findings indicated that risk for first or recurrent VT in a relative of a proband who had thrombophilia was strongly dependent on the type of hereditary thrombophilic defect: Deficiencies of natural anticoagulants (i.e., ACS) were associated with higher risks for first VT than were more-common defects (i.e., FVL, ProGA, and high FVIII levels). These results also showed that more-severe ACS-related thrombophilias tended to occur in patients who had VT at younger ages and who were more likely to have recurrences after anticoagulants were discontinued. When clinicians implement screening strategies, priority should be given to testing probands with severe thrombophilias and their immediate family members.

— David Green, MD, PhD

Published in Journal Watch Oncology and Hematology June 30, 2009

Citation(s):

Lijfering WM et al. Selective testing for thrombophilia in patients with first venous thrombosis: Results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 2009 May 21; 113:5314.

• Original article (Subscription may be required)
• Medline abstract (Free)

Reader Remarks:

Read all Reader Remarks on this article

• Testing for thrombophilia in patients with first venous thrombosis
  James S. Adamson, 7 Jul 2009 12:50 PM EST
  How does this recommendation fare with the JAMA article of 17 Jun 09 which indicated little benefit of this testing... [more]