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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).
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.
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