Making the tough decisions on FVL
Back to Cover Story
William Check, PhD
The American College of Medical Genetics published in March 2001 the
first professional guidelines on factor V Leiden testing (www.acmg.net).
Chair of the ACMG committee in charge was Wayne Grody, MD, PhD, professor
in the departments of Pathology, Pediatrics, and Human Genetics at
the University of California, Los Angeles, and director of UCLAMedical
Center’s DNA diagnostic laboratory. "Our guidelines mostly coincide
with the CAP recommendations," says Dr. Grody, who chairs the CAP’s
Molecular Pathology Committee and CAP/ACMG Biochemical and Molecular
Genetics Resource Committee.
Deciding who should be offered FVL testing generated considerable
debate. Perhaps the entire U.S. population should be screened: The
carrier rate is about seven percent in Caucasians and carriers are
at five- to 10-fold increased risk of venous thromboembolism. "That
sounds like a lot," Dr. Grody says, "but the baseline risk is very
low, especially in younger adults." And what would you do for asymptomatic
carriers? Anticoagulants carry a risk of bleeding that is higher
than the risk of VTE. "In the end, we did not recommend population
screening or prenatal or newborn screening," Dr. Grody says. The
main indication for FVL testing remains unprovoked VTE in a person
under the age of 50. The committee did not recommend testing relatives
of persons who test positive, but they did not rule it out.
The other major consideration is women using oral contraceptives.
A woman using OCs who is also an FVL carrier has a 35-fold increased
risk of VTE. "It is surprising to many people that we did not recommend
FVL testing in these women," Dr. Grody says. "I am still getting
critical phone calls about it." The committee based its decision
on a published study that calculated that 2.5 million women would
need to be screened to prevent one death from VTE. In the process
90,000 carriers would be identified. If all 90,000 carriers selected
less effective non-OC birth control, more would die of pregnancy
complications than would die of the consequences of FVL.
Concomitant or followup screening tests were also debated, especially
prothrombin G20210A, which has synergistic risk with FVL. UCLA hematologists
said they prefer to order tests separately. But the ACMG committee
recommended that patients positive for FVL be considered for other
common thrombophilic factors with a similar phenotype for which
testing is easy and available. "At this point, only prothrombin
fits," Dr. Grody says. "I think it ought to be done."
"We didn’t go into methodology very much," Dr. Grody says, "but
we did consider whether to do functional assays for FVL rather than
direct DNA tests." DNA-based tests have advantages: They are not
affected by concomitant therapy and better distinguish heterozygotes
Finally, the committee said neither informed consent nor formal genetic counseling
was needed with FVL testing. However, the physician should tell the patient
that the test result could have implications for family members.