Search our Test Catalog. Specify what to search (name, test code, titles, everywhere) and how to search (begins with, contains)

Unit Code 81419:
Factor V Leiden (R506Q) Mutation, Blood

Print Friendly View
Print Page Email Page

Useful For

Direct mutation analysis should be reserved for patients with

clinically suspected thrombophilia and:

   -APC-resistance proven or suspected by a low APC-resistance ratio

   -Family history of the FV Leiden mutation

 

Additionally, it may be appropriate to screen those women contemplating

oral contraceptive use or pregnancy, with consideration of an alternative

form of contraceptive therapy or VTE prophylaxis during pregnancy

and/or the post-partum state for women with FV Leiden allele.

 

Knowledge of the FV Leiden allele status may alter anticoagulation

management of VTE patients.

Clinical Information

Venous thromboembolism (VTE) is a syndrome of deep vein

thrombosis and its complication, pulmonary embolism. Recent

work highlights the role of both genetic heterogeneity and

genetic/environmental interaction in the etiology of VTE.(1)

 

Plasma from 12-52% of VTE patients is resistant to the

anticoagulant effect of activated protein C (APC-resistance).(2)

Approximately 90% of patients with hereditary APC-resistance have

a single nucleotide mutation of the coagulation Factor V gene that

encodes for an arginine (R) to glutamine (Q) substitution at position

506 of the Factor V protein (FV Leiden).(3,5)

 

In general, the FV Leiden allele population carrier frequency

parallels the incidence of VTE in that population. For example, the

FV Leiden allele is common among populations of Scandinavian

and European ancestry (3-7%), where the annual VTE incidence

approaches 120 per 100,000. In contrast, the FV Leiden allele has

yet to be detected in Asian or Japanese populations, where VTE

incidence is extremely low.

 

Heterozygous FV Leiden carriers have an 8-fold risk increased for

VTE while homozygous carriers have an 80- to 100-fold increased risk.  

Other genetic disorders causing deficiency of antithrombin, protein C,

or protein S, or hyperhomocysteinemia are independently associated

with VTE.  However, interaction of these genetic disorders with the FV

Leiden allele markedly compounds the risk for VTE.  Genetic and

environmental (clinical) risk factors also interact to compound the risk

for VTE.  The VTE risk is increased 30-fold among women

heterozygous FV Leiden carriers receiving oral contraceptives, and

the VTE risk during pregnancy or the post-partum period also is

increased.  Homozygous FV Leiden carriers have an increased risk

for recurrent VTE while the risk for heterozygous carriers appears to

be no different than the risk for noncarriers with VTE.

 

Controversy exists regarding the association between the FV R506Q

allele and arterial occlusive disease (e.g., coronary artery disease,

myocardial infarction, stroke); more studies are needed in order to

answer this question.

 

Direct detection of the FV Leiden gene mutation can be performed

on patient blood leukocyte genomic DNA.

Reference Values

Negative

Interpretation

The interpretive report will include specimen information, assay

information, background information, and conclusions based on the

test results (normal, heterozygous FV Leiden, homozygous FV Leiden).

Cautions

This direct mutation analysis will not detect individuals with

APC-resistance caused by mechanisms other than the FV Leiden.

 

While genetic disorders causing antithrombin, protein C, protein S

deficiency, or hyperhomocysteinemia are independently associated

with VTE; interaction of these genetic disorders with the FV Leiden

allele markedly compounds the risk for VTE.

 

Environmental (clinical) risk factors also interact to produce VTE.

 

On-site Special Coagulation Clinic/Laboratory, Thrombophilia Center,

and/or Medical Genetics consultations are available for registered

Mayo Clinic patients and may be especially helpful in complex cases

or in situations where the diagnosis is atypical or uncertain. Phone

consultations are available for Mayo Medical Laboratories (MML) clients

Special Instructions and Forms

• MayoConnect Additional Test Information 
• Informed Consent Form for DNA Testing 

Clinical Reference

1.   Nichols WL, Heit JA:  Activated protein C resistance and thrombosis.

      Mayo Clin Proc 1996;71:897-898

 

2.   Dahlback B, Carlsson M, Svensson PJ: 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 Acad Sci USA

      1993;90:1004-1008

 

3.   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

 

4.   Grody WW, Griffin JH, Taylor AK, et al:  American college of

      medical genetics consensus statement on Factor V Leiden

      mutation testing. Genet Med 2001;3:139-148

 

5.   Press RD, Bauer KA, Kujovich JL, Heit JA:  Clinical utility of

      Factor V Leiden (R506Q) testing for the diagnosis and

      management of thromboembolic disorders. Arch Path Lab

      Med 2002;126:1304-1318

Key