Factor V Leiden Polymorphism (FVR506Q)
Resistance to activated protein C (APC) is a frequently identified abnormality in patients with venous thrombosis. In patients presenting with an initial venous thromboembolic event, as many as 21% have APC resistance. Furthermore, in patients with recurrent venous thrombosis, as many as 60% have APC resistance. APC resistance has also been associated with atypical thromboembolic complications, including portal vein thrombosis and cerebral sinus thrombosis. Exposure to certain environmental risk factors, such as surgery, pregnancy, or oral contraceptives, can further increase the risk for a venous thrombotic event. Although APC resistance is a common finding in patients with venous thrombosis, it is seldom identified as a risk factor for arterial thrombosis.
Laboratory screening for APC resistance consists of clotting assays that measure the degree of prolongation of the plasma clotting time upon the addition of APC. In more than 90% of cases, APC resistance is linked to a single polymorphism in the factor V gene. This polymorphism, known as Factor V Leiden (Factor VR506Q), involves a single base pair substitution at position 1691 in the factor V gene, resulting in substitution of the arginine (R) at position 506 by glutamine (Q). This substitution blocks an important APC-cleavage site in factor Va after position 506, thereby resulting in a decreased ability of APC to inactivate the procoagulant factor Va. This single polymorphism results in the observed hypercoagulable state that leads to an increased risk for venous thromboembolism.
In general, it is recommended that initial screening of a patient with a venous thromboembolic event for this polymorphism use a plasma-based clotting assay. This is recommended because the cost of the clotting assay is significantly less than the DNA-based assay and a normal clotting assay is very specific for a normal factor V genotype. However, it is recommended that DNA based analyses be performed on all patients with abnormal plasma-based APC resistant clotting assays, in order to confirm the diagnosis as well as determine the genotype of the affected individual.
Factor V Leiden Mutation by Polymerase Chain Reaction (PCR)
This assay utilizes genomic DNA isolated from the buffy coat to determine the genotype of the patient. A portion of the factor V gene is amplified by the polymerase chain reaction (PCR), following which the DNA is restricted with the enzyme MnlI. The DNA is then analyzed by agarose gel electrophoresis and compared to restricted samples from a normal individual and an individual who is homozygous for the Factor V Leiden mutation.
CPT Codes: 83890, 83892, 83894, 83898, 83192
Ordering Information and Specimen Requirements:
Factor V Leiden Mutation:
Specimen Requirements: Whole Blood (EDTA or 3.2% Sodium Citrate)
Transport temperature: Ambient (22 - 24° C)
Specimen Stability: 7 days at 22 - 24° C
Assay Setup days: Tuesday
Assay Time: 2-4 days
Report Turn-around-Time: 1 week (via Fax)
Call (800) 441-1416 or (919) 684-6366 to request shipping instructions, test requisitions, collection requirements, and additional information.
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Methylenetetrahydrofolate Reductase (MTHFR) Mutation
Protein C Functional Assay
Protein S Functional Assay
Prothrombin (G20210A) Gene Mutation
Last Modified: May 8, 2000