Genetic Testing for DVT Risk Still Controversial


'[Referring physicians] say, “Does this patient have Factor V Leiden?” I talk them out of it.' DR. WEITZ

ATLANTA — An inherited mutation, Factor V Leiden, puts people at risk for life-threatening blood clots. Carriers can be identified with a simple blood test, so why not use it?

“Genetic testing is highly controversial. This is really not ready for prime time yet,” Dr. David Ginsberg advised during a special session on venous thromboembolism at the annual meeting of the American Society of Hematology.

Factor V Leiden has been associated with risk of miscarriage and possibly other complications, but most women with the mutation have normal pregnancies, he noted. Likewise, while Factor V Leiden has been linked to increased risk of venous thromboembolism in women taking oral contraceptives, they are not contraindicated.

The central issue for Dr. Ginsberg was not whether Factor V Leiden is a risk factor, but what that means and what, if anything, would be done differently when treating patients who test positive.

About 5% of people of European origin have Factor V Leiden, according to Dr. Ginsberg, the James V. Neel Distinguished University Professor of Internal Medicine and Human Genetics at the University of Michigan, Ann Arbor. It “clearly increases” relative risk, compared with no mutation in Factor V, but most people with the mutation do not develop blood clots.

“Nature would not allow this to be in 5% of the population, if it was really all that bad,” he said, speculating that Factor V Leiden might confer a benefit in some patients who develop venous thromboembolism. “Factor V Leiden might not always be 'bad' for you,” he said.

Dr. Ginsberg cited two human studies that found deep venous thrombosis (DVT) was less likely to progress to pulmonary embolism in people with Factor V Leiden. Also, he noted that in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial evaluating recombinant human activated protein C (rhAPC), or drotrecogin alfa activated, in patients with severe sepsis, 28-day all-cause mortality was lower in 65 patients with Factor V Leiden.

Based on current knowledge, a positive test for Factor V Leiden would not change any treatments, Dr. Ginsberg continued. Patients still would receive heparin or warfarin for acute thrombosis and be given warfarin for 31/2 months as prophylaxis after a first event. If patients have recurrent thromboses, warfarin prophylaxis would be extended, possibly becoming a lifelong intervention.

In the future, he suggested Factor V Leiden testing might be useful when choosing primary therapy and duration of therapy for thrombosis. Likewise, the presence of Factor V Leiden might indicate the need for thrombosis prophylaxis during pregnancy, postoperatively, and after a first thrombotic event. And women may be screened for Factor V Leiden before oral contraceptives are prescribed.

But none of this is done now, and he said more data are needed to support genotype-specific prophylaxis or therapy. Meanwhile, a positive finding could be cause for anxiety and hypervigilance. “My plea is that, until there is clear-cut evidence, testing should be used judiciously,” he said.

In an interview after the session, Dr. Jeffrey Weitz, another speaker at the special session, said he “very much agreed” with Dr. Ginsberg and does not test for Factor V Leiden unless a patient insists. Most patients requesting the test have thrombosis and are referred by primary care physicians, according to Dr. Weitz of Hamilton Civic Hospitals Research Centre in Ontario. “They say, 'Does this patient have Factor V Leiden?' “he said. “I talk them out of it.”

For another speaker, Melanie Bloom, a national patient spokeswoman for the Coalition to Prevent Deep Vein Thrombosis, the test is not so easy to rule out, however. Her husband, David Bloom, died of a DVT that led to pulmonary embolism while covering the Iraq war for NBC news. After his death at the age of 39, the family became aware that he had been at high risk for DVT.

When their three young daughters reach the age where pregnancy and contraception are an issue, Mrs. Bloom said she would want to know whether they have an inherited risk. “David's life could have been saved with awareness and knowledge,” she said. “Less than a quarter of physicians educate high-risk patients about DVT.”

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