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Factor V Leiden, prothrombin G20210A do not predict recurrent venous thromboembolism

Stephen Padilla
02 Oct 2017

Elderly patients with a first unprovoked venous thromboembolism may not benefit from testing for genetic thrombophilia, a recent study suggests.

“[O]ur results demonstrate that in elderly patients with a first unprovoked venous thromboembolism, genetic thrombophilia is not associated with an increased risk of venous thromboembolism recurrence,” researchers said.

The Factor V Leiden and the prothrombin G20210A mutation were genotyped in 354 consecutive patients aged ≥65 years with a first unprovoked venous thromboembolism from nine Swiss hospitals, with both patients and physicians blinded to testing results. Recurrent symptomatic venous thromboembolism during follow-up was the main outcome.

Researchers used competing risk regression to examine the association of the Factor V Leiden and the Prothrombin G20210A mutation with venous thromboembolism recurrence, adjusting for age, sex and periods of anticoagulation as a time-varying covariate.

Of the patients, 9.0 and 3.7 percent had a Factor V Leiden and a prothrombin G20210A mutation, respectively. [Am J Med 2017;130:1220.e17–1220.e22]

At 36 months of follow-up, the cumulative incidence of recurrent venous thromboembolism was 12.9 percent (95 percent CI, 5.1 to 30.8 percent) of patients with a Factor V Leiden and 18.5 percent (4.9 to 56.5 percent) of those with a prothrombin G20210A mutation compared with 16.7 percent (12.5 to 22.1 percent) of patients without mutation (p=0.91 by the log-rank test).

Both the Factor V Leiden (subhazard ratio [sub-HR], 0.98; 0.35 to 2.77) and the prothrombin G20210A mutation (sub-HR, 1.15; 0.25 to 5.19) did not correlate with recurrent venous thromboembolism after adjustment.

“Prior prospective studies demonstrated that genetic thrombophilia is only a very modest predictor of recurrence (relative risk, 1.4 to 1.8) in younger patients with unprovoked venous thromboembolism,” researchers said. [Arch Intern Med 2006;166:729–736]

“Our results confirm that the prognostic impact of genetic thrombophilia is even less relevant in the elderly, possibly because clinical factors, such as comorbid conditions, may be stronger drivers of venous thromboembolism recurrence than genetic thrombophilic factors,” they added. [Arch Intern Med 2000;160:761–768]

An earlier case-control study found that testing for Factor V Leiden and prothrombin G20210A mutation in patients with a first venous thromboembolism was not associated with a lower incidence of recurrent venous thromboembolism. Likewise, testing for genetic thrombophilia had no impact on medical management in 77 percent of tested patients. [J Thromb Haemost 2008;6:1474–1477; J Thromb Haemost 2007;5:1979–1981]

“Given the high costs of testing (approximately $300) and its presumed lack of benefit, genetic thrombophilia testing is not useful in elderly patients with a first unprovoked venous thromboembolism,” according to researchers. [Stroke 2003;34:1826–1827; Health Technol Assess 2009;13]

“Although current guidelines do not support genetic thrombophilia testing for predicting recurrent venous thromboembolism, testing continues to be done in one of five patients aged more than 50 years with a first unprovoked venous thromboembolism,” they added. [Chest 2008;133:454S–545S; Semin Respir Crit Care Med 2017;38:107–120; Thromb Res 2009;124:174–177]

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