Laboratory tests can accurately detect two clotting-factor mutations that raise risk of blood clots

Research Activities, October 2010, No. 362

The various laboratory tests to identify specific mutations in two proteins in the human clotting system, factor V Leiden (FVL) and prothrombin G20210A, appear to be accurate, according to a new review of published studies. The presence of these single-base mutations in the factor V or prothrombin genes increases the patient's risk for deep vein blood clots or fatal and nonfatal pulmonary embolisms. Factor V Leiden refers to a single base change in the gene (Factor V G1691A) that encodes an amino acid substitution (Arg506Gln), which results in inactivation of factor V at a lower rate. Since active Factor V is involved in clot formation, reducing its rate of inactivation leads to more clot formation. The prothrombin (Factor II) mutation gene, G20210A, is associated with an elevation of prothrombin levels to about 30 percent above normal in heterozygotes (having one copy) and to 70 percent above normal in homozygotes (having two copies).

Both commercial and experimental tests demonstrated at least 95 percent (and, in many cases, 100 percent) analytical validity (i.e., validity of the test in the laboratory) when compared with a reference standard for each mutation, the researchers found. Three studies looked at quality assurance among laboratories conducting genetic testing, including tests for FVL and prothrombin G20210A. These studies, conducted in the United Kingdom, Australia, and Italy, found most laboratories gave accurate results on known samples carrying these mutations. However, a few laboratories were responsible for many of the mistakes—in one study, 3 of 39 laboratories accounted for 46 percent of the errors.

To determine how accurate the genetic tests for these two mutations were, the researchers reviewed over 7,000 articles about commercial and experimental tests for these mutations published during the years 2000 through 2008. The researchers found 66 papers in which at least 10 patient samples were compared with traditionally accepted reference tests for a mutant (FVL or prothrombin G20210A) allele. Forty-one studies compared at least two methods for FVL detection, 23 studies did the same for prothrombin G20210A, and 12 studies investigated multiple technologies that tested for both alleles at once. The study was funded in part by the Agency for Healthcare Research and Quality (Contract No. 290-2007-1006).

More details are in "Analytic validity of genetic tests to identify factor V Leiden and prothrombin G20210A," by Ashkan Emadi, M.D., Ph.D., Matthew T. Crim, M.Sc., M.A., Daniel J. Brotman, M.D., and others in the April 2010, American Journal of Hematology 85(4), pp. 264-270.

Current as of October 2010
Internet Citation: Laboratory tests can accurately detect two clotting-factor mutations that raise risk of blood clots: Research Activities, October 2010, No. 362. October 2010. Agency for Healthcare Research and Quality, Rockville, MD.