In summary, although Factor V Leiden and prothrombin gene defects are associated with increased risk of recurrent VTE, the magnitude of the risk increase is modest and, therefore, should not alter duration of therapy.
Acquired thrombophilia.
It appears that the only thrombophilic state that might have a significant impact on the risk of recurrence is the antiphospholipid syndrome. The cessation of warfarin therapy in patients with thrombosis associated with antiphospholipid antibodies carries a 69% risk of recurrent thrombosis within a year.23 Some studies have suggested that the presence of specific antibodies (i.e. anticardiolipin antibodies) is associated with increased risk in patients with antiphospholipid syndrome.24
However, at present, all patients with VTE and antiphospholipid syndrome should be candidates for lifelong anticoagulation. Antiphospholipid antibody testing should be performed in patients with a suggestive history, including those with recurrent fetal loss or a single fetal loss after 10 weeks, or known collagen vascular disease.25
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Table 3. Indications for Thrombophilia Testing
The role of provoked vs. unprovoked VTE.
Identifying whether a VTE is provoked or unprovoked has been shown to be an important predictor of recurrence. For example, one prospective, cohort study found two-year recurrence rates of zero in patients with a surgery or pregnancy-related VTE, 9% with other provoked VTE, and 19% with unprovoked VTE.26 In the same study, thrombophilia testing failed to reliably predict recurrence risk. Patients with unprovoked VTE who were tested and found to not have a defect were at equally high risk of recurrent VTE as those found to have a thrombophilia.27
The most significant predictor for VTE recurrence is whether the first event was provoked, and thrombophilia testing offers little additional prognostic information.28
VTE as a multifactorial disorder.
It is becoming increasingly clear that VTE is multifactorial disorder, caused by the interactions of genotypic, phenotypic, and environmental factors. In the case of an unprovoked VTE, the patient already carries a significantly elevated risk for recurrence, and further testing for known causes of thrombophilia appears to add very little additional information. The optimal duration of anticoagulation for unprovoked VTE is unclear, but current guidelines suggest at least three months—and clinicians should consider lifelong treatment.
In the vast majority of cases, testing for thrombophilia has no impact on the management of VTE and is not warranted. In patients with antiphospholipid-antibody syndrome, given the high risk of recurrence, long-term anticoagulation after a first VTE might be indicated. In select patients with a clinical picture suggestive of antiphospholipid-antibody syndrome, or a strong family history, testing should be considered.
Back to the Case
Our patient appears to have an unprovoked VTE. She should receive regular anticoagulation with warfarin, with a goal INR of 2 to 3, for at least three months. Lifelong anticoagulation therapy should be considered. Testing for heritable thrombophilia will not change the current management or treatment duration and, hence, is not indicated. However, the patient’s history is suggestive of antiphospholipid-antibody syndrome, so she should be tested. If the diagnosis of antiphospholipid syndrome is made, lifelong anticoagulation should be considered.
Bottom Line
Unprovoked VTE provides the strongest predictor for recurrence. Thrombophilia testing adds little in predicting recurrence and rarely is indicated.
Dr. Stehlikova is a clinical hospitalist in the division of hospital medicine, department of medicine, at Albert Einstein College of Medicine and Montefiore Medical Center in Bronx, N.Y. Dr. Martin is director of the Einstein Hospitalist Service. Dr. Janakiram is a fellow in the department of hematology at Einstein, and Dr. Korcak is an instructor at Einstein in the department of medicine and director of the Weiler Medical Service. Dr. Galhotra is associate director for inpatient quality in the department of medicine at Einstein; Dr. Averbukh is an academic hospitalist; and Dr. Southern is chief of the division of hospital medicine at Einstein.