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Bioheart Genotype Tests: Related Info BIOHEART Genotyping, Inc.

Factor VLeiden:

DEFECT: Substitution of glutamine for arginine at AA position 506 Frequency: 2%-5% in the general population; 20% in patients with venous thrombosis Associated Risk: Heterozygotes have about 8-fold increased risk of venous thrombosis. Homozygotes have a 91 fold increased risk compared to normal individuals.

MODE OF ACTION: Poor plasma anticoagulant response to activated protein C (APC resistance) is the most commonly observed inherited defect associated with thrombotic risk. The Factor VLeiden mutation renders the protein resistant to inactivation by APC. Method of detection: Allele-specific PCR on DNA isolated from leukocytes found in whole blood.

POSSIBLE CLINICAL UTILITY: Tests for FVL should be done on:

  • People with multiple thrombotic events, family history of thrombotic events, thrombotic events at younger age (under 40-45), thrombosis at an unusual anatomical site: outside the veins of legs, pelvis, or lungs.
  • Immediate family members of patients carrying the mutation.
  • Women who are at increased risk for venous thrombosis, especially if they are taking oral contraceptives or are pregnant or have had fetal loss should also be screened for this risk factor.

Finding the mutation represents a permanent risk factor and could influence the length of therapy to prevent future events.

NOTE: Numerous studies have found no association between heart disease and the factor V Leiden polymorphism. We have not included these studies in the list of references. If you would like to review these publications, please and we will send you copies of these articles.


    1. Doggen CJ, Cats VM, Bertina RM, Rosendaal FR.; Interaction of coagulation defects and cardiovascular risk factors: increased risk of myocardial infarction associated with factor V Leiden or prothrombin 20210A. Circulation 1998 Mar 24;97(11):1037-41

      The risk of myocardial infarction in the presence of the Prothrombin 20210 mutation (AG genotype) was increased by 50% (odds ratio, 1.5; 95% confidence interval [95% CI], 0.6 to 3.8). The risk of myocardial infarction for carriership of factor V Leiden mutation was increased by 40% (odds ratio, 1.4; 95% CI, 0.8 to 2.2). When a coagulation defect was present (ie, the 20210 AG prothrombin genotype or the factor V Leiden mutation), the risk of myocardial infarction for carriers versus noncarriers was 1.4 (95% CI, 0.9 to 2.2). This risk was substantially increased when one of the major cardiovascular risk factors of smoking, hypertension, diabetes mellitus, or obesity also was present, with odds ratios varying between 3 and 6. These risks exceeded those of the single effects of the cardiovascular risk factors (ie, in the absence of the coagulation defect). We conclude that in men the 20210 G-->A variant of prothrombin is associated with an increased risk of myocardial infarction. The combined presence of major cardiovascular risk factors and carriership of a coagulation defect increases the risk considerably.

    2. Eskandari MK, Bontempo FA, Hassett AC, Faruki H, Makaroun MS.; Arterial thromboembolic events in patients with the factor V Leiden mutation. Am J Surg 1998 Aug;176(2):122-5.

      Thirty patients were found to be heterozygous for the Factor V Leiden mutation. The mean age for 16 patients sustaining a cerebrovascular accident was 44.1 and majority of this patient subgroup were younger than 50 years of age. Thirteen of the patients with an acute myocardial infarction were relatively young with a mean age of 45.5, and majority were also less than 50 years of age. This study demonstrates an association between the factor V Leiden mutation and the development of unexplained arterial thromboembolic events, especially in younger patients without existing atherosclerotic disease.

    3. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH.; High risk of thrombosis in patients homozygous for factor V Leiden. Blood 1995 Mar 15;85(6):1504-8

      The relative risk for thrombosis was increased 7-fold for individuals heterozygous for the Factor V Leiden mutation, and 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime. Patient size=474

    4. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH.; Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994 May 5;369(6475):64-7

      This study demonstrated that resistance to activated protein C (APC) is associated with heterozygosity or homozygosity for a single point mutation in the factor V gene (at nucleotide position 1,691, G-->A substitution) which predicts the synthesis of a factor V molecule (FV Q506, or FV Leiden) that is not properly inactivated by APC. The allelic frequency of the mutation in the Dutch population is approximately 2% and is at least tenfold higher than that of all other known genetic risk factors for thrombosis (protein C, protein S, antithrombin10 deficiency) together.

    5. Svensson PJ, Dahlback B.; Resistance to activated protein C as a basis for venous thrombosis.
    N Engl J Med 1994 Feb 24;330(8):517-22

      The study was conducted to determine the prevalence of resistance to activated protein C (APC) in patients with venous thrombosis. Forty-five percent of patients had a family history of thrombosis. A significant (P < 0.001) difference in APC ratios was observed between the controls and the patients with thrombosis. For 33 percent of patients, the APC ratio was below the 5th percentile of the control values, although the results of the family studies suggested that the prevalence of APC resistance may be even higher (approximately 40 percent) in the patients with thrombosis. CONCLUSIONS. There was a high prevalence of APC resistance among young persons with a history of venous thrombosis, and this resistance appeared to be inherited as an autosomal dominant trait. Patient size: 104

    6. Varela ML, Adamczuk YP, Martinuzzo ME, Forastiero RR, Klein FR, Rossi AS, Carreras LO.;
    Early occlusion of coronary by-pass associated with the presence of factor V Leiden and the prothrombin 20210A allele: case report. Blood Coagul Fibrinolysis 1999 Oct;10(7):443-6

      A 56-year-old man who developed coronary artery disease since 1980 without any known risk factor and underwent a cardiopulmonary by-pass in 1997. The patient is heterozygous for factor V Leiden mutation and has the variation 20210GA of the prothrombin gene and high levels of LPa. Due to these findings, oral anticoagulation was added to the aspirin treatment, and the patient is in a good condition 11 months later.

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