Factor V Leiden (R506Q) Mutation, Blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Venous thromboembolism includes deep vein thrombosis and its complication, pulmonary embolism. Plasma from 12% to 20% of venous thromboembolism patients is resistant to the anticoagulant effect of activated protein C (APC resistance). Essentially all patients with hereditary APC resistance have a single nucleotide mutation of the coagulation factor V (fV) gene (F5 rs6025), which encodes for an arginine (R) to glutamine (Q) substitution at position 506 of the factor V protein (fV R506Q). The factor V Leiden (R506Q) gene mutation test is a direct mutation analysis of patient blood leukocyte genomic DNA.
We recommend the coagulation-based activated protein C (APC)-resistance ratio (mixing with factor V-deficient plasma) as the initial screening assay for APC-resistance. Depending on the assay system, the APC-resistance ratio may be indeterminate for patients with a lupus anticoagulant or extremely high heparin levels.
Factor V Leiden mutation testing should be reserved for patients with clinically suspected thrombophilia and: 1) APC-resistance proven or suspected by a low or borderline APC-resistance ratio, or 2) a family history of factor V Leiden.
The interpretive report will include specimen information, assay information, background information, and conclusions based on the test results (normal, heterozygous fV R506Q, homozygous fV R506Q).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This direct mutation analysis will not detect individuals with activated protein c (APC)-resistance caused by mechanisms other than the fV R506Q.
Special Coagulation Clinic and/or Medical Genetics consultations are available for DNA diagnosis cases, and may be especially helpful in complex cases or in situations where the diagnosis is atypical or uncertain.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Dahlback B, Carlsson M, Svensson PR: Familial Thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acac Sci USA 1993;90:1004-1008
2. Bertina RM, Koeleman BP, Koster T, et al: Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-67
3. Zoller B, Svensson PJ, He X, Dahlback B: Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994;94:2521-2524
4. Hall JG, Eis PS, Law SM, et al. Sensitive detection of DNA polymorphisms by the serial invasive signal amplification reaction. Proc Natl Acad Sci USA 2000;97:8272-8277
5. Heit JA: Thrombophilia: clinical and laboratory assessment and management. In Consultative Hemostasis and Thrombosis. Fourth edition. Edited by CS Kitchens, BM Alving, CM Kessler. Saunders 2012