At a Glance
Why Get Tested?
When to Get Tested?
When you have had an unexplained blood clot (thrombotic episode), especially when you are less than 50 years old, have recurrent DVT or VTE episodes, experienced DVT or VTE during pregnancy, had DVT at unusual sites, or have a strong family history of thrombosis
A blood sample drawn from a vein in your arm
Test Preparation Needed?
The Test Sample
What is being tested?
Factor V Leiden and prothrombin 20210 (PT 20210) are genetic mutations that are associated with an increased risk of developing inappropriate blood clots. Two separate tests for these mutations are often performed together to detect the mutations and help determine if an individual has an inherited risk for excessive clotting.
Factor V and prothrombin are coagulation factors, two of a group of proteins essential for proper blood clot formation. When an injury occurs and bleeding starts, a process called hemostasis begins to form a plug at the injury site to help stop the bleeding. Blood cells called platelets adhere to and aggregate at the injury site, and a coagulation cascade begins to activate coagulation factors in sequence. Eventually, a blood clot forms. Once the area has healed, the blood clot dissolves.
There must be an adequate number of each of the coagulation factors, and each must function normally in order for a stable blood clot to form and then dissolve when no longer needed. Too little of the factors, or ones that are dysfunctional, can lead to bleeding or inappropriate clotting (thrombosis).
Factor V Leiden and PT 20210 are two mutations that individuals may inherit from their parents that may cause an increased risk of excessive clotting. A person may inherit one mutated gene copy and be heterozygous or may inherit two mutated gene copies and be homozygous. This may determine to what extent the person is affected.
- During hemostasis, factor V is normally inactivated by a protein called activated protein C (APC) to prevent the blood clot from growing too large. But a Factor V Leiden genetic mutation can lead to an altered factor V protein that resists inactivation by APC. The result is that clotting remains more active than usual, increasing risks of a blood clot forming in the deep veins of legs (DVT) or breaking off and blocking a vein (venous thromboembolism or VTE).
Factor V Leiden mutation is the most common inherited predisposition to abnormal clotting in the United States and it is most common in the Caucasian population. Between 3 and 8 percent of U.S. Caucasians carry one copy of the factor V Leiden mutation and about 1 in 5,000 people have two copies of the mutation. While homozygous cases of Factor V Leiden are more rare, they also carry a higher risk of thrombosis. People with two copies of the mutation may have up to 80 times the risk of thrombophilia while those with one copy have 4 to 8 times the risk, compared to those who do not carry the mutation.
- During normal blood clotting, an enzyme splits prothrombin to form thrombin. A mutation in the gene that codes for prothrombin called prothrombin 20210 can lead to increased amount of prothrombin, abnormal clotting, and an increased risk of a DVT or VTE.
A person with a PT 20210 mutation may be heterozygous or homozygous, although it is very rare to find individuals who are homozygous. The affected heterozygous person will have a mild to moderate increase in their thrombin production, which is associated with 2.5 to 3 fold greater risk of developing a VTE in Caucasians; there is not enough information about risk in those who are homozygous. Although PT 20210 is less common in the U.S. than Factor V Leiden (about 1-2% of the general population), it is also more prevalent in Caucasians than in those of other ethnic backgrounds.
These mutations are independent and are tested separately, but the tests are often performed at the same time as part of the investigation of a blood clot (thrombotic episode) in someone who is suspected of having an inherited risk factor for an excessive clotting (hypercoagulable) disorder. Each test is used to identify whether or not the specific mutation is present and to determine whether the person has one copy (heterozygous) or two copies (homozygous) of that mutation.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Sources Used in Current Review
Mayo Clinic Staff. (2012 September 6). Factor V Leiden. Mayo Clinic. Available online at http://www.mayoclinic.org/diseases-conditions/factor-v-leiden/basics/definition/con-20032637 through http://www.mayoclinic.org. April 2014.
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Shah, S. et al. (Updated August 31, 2012). Genetics of Venous Thromboembolism. Medscape. Available online at http://emedicine.medscape.com/article/1797779-overview through http://emedicine.medscape.com. Accessed April 2014.
Hart, K. et. al. (Updated 2014 February). Hypercoagulable States – Thrombophilia. ARUP Consult. Available online at http://www.arupconsult.com/Topics/Thrombophilia.html?client_ID=LTD through http://www.arupconsult.com. Accessed April 2014.
Schwartz, R. et al. (Updated 2013 September 27). Factor II. Medscape. Available online at http://emedicine.medscape.com/article/209742-overview through http://emedicine.medscape.com. Accessed April 2014.
Pagana, K. D. & Pagana, T. J. (© 2012). Mosby's Diagnostic and Laboratory Test Reference 11th Edition: Mosby, Inc., Saint Louis, MO. Pp 421-422.
Berg, A. et al. Recommendations from the EGAPP Working Group: Routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members. Genetics in Medicine (2011) 13, 67–76; doi:10.1097/GIM.0b013e3181fbe46f. Available online at http://www.nature.com/gim/journal/v13/n1/full/gim9201111a.html through http://www.nature.com/. Accessed April 2014.
Patel, K. et al. (Updated 2014 April 15). Deep Venous Thrombosis. Medscape. Available online at http://emedicine.medscape.com/article/758140-overview through http://emedicine.medscape.com. Accessed April 2014.
Ghosh, Amit. (© 2010). Mayo Clinic Internal Medicine Review. 9th edition: Oxford University Press, Pg. 394.
Sources Used in Previous Reviews
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Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.
Coagulation Test Panels. Florida Hospital Cancer Institute, Clinical and Research Laboratories [Online information]. Available online at http://www.fhci-labs.com/researchlabs/clinicallabs/hemostasisandthrombosis/panels.htm through http://www.fhci-labs.com.
Confusing Coagulation Test Names. UAB Coagulation Service, Univ of Alabama at Birmingham [Online information]. Available online at http://peir.path.uab.edu/coag/article_187.shtml through http://peir.path.uab.edu.
Check, W. (1999 September). Labs Home In On Mutant Alleles. CAP Today, In the News [On-line Journal]. Available online at http://www.cap.org/captoday/archive/1999/cov999.html through http://www.cap.org.
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Prothrombin Gene Mutation 20210A [11 paragraphs]. University of Illinois - Urbana/Champaign, Carle Cancer Center, Hematology Resource Page, Patient Resources [On-line information]. Available online at http://www-admin.med.uiuc.edu/hematology/PtProthrombin.htm through http://www-admin.med.uiuc.edu.
Press, R. et. al. (2002). Clinical Utility of Factor V Leiden (R506Q) Testing for the Diagnosis and Management of Thromboembolic Disorders. Arch Pathol Lab Med 126: 1304-1318 [Online pdf of journal article]. PDF available for download at http://www.access-genetics.com/Arch_Pathol_Lab_Med_Vol%20126_Nov_2002_3.pdf through http://www.access-genetics.com.
(2001 January 10, Modified). Coagulation Test Descriptions, Factor V Leiden (Activated Protein C Resistance Pcr Assay) and Prothrombin (G20210A) Gene Polymorphism (PTG G20210A). Clinical Coagulation Laboratory, A division of Duke University Regional Referral Laboratory Services [Online information]. Available online at http://pathology.mc.duke.edu/coag/TestDes.htm through http://pathology.mc.duke.edu.
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Pagana, Kathleen D. & Pagana, Timothy J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 430-431.
Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry. AACC Press, Washington, DC. Harris, N. et. al. Chapter 19: Assessment of Hemostasis in the Clinical Laboratory, Pp 227-239.
Kujovich, J. (2007 February 12, Update). Factor V Leiden Thrombophilia. GENEReviews [On-line information]. Available online at http://www.genetests.org/query?dz=factor-v-leiden through http://www.genetests.org. Accessed on 3/14/07 .
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Ornstein, D. and Cushman, M. (2003). Factor V Leiden. Circulation 2003:107;94-97 [On-line information]. PDF available for download at http://circ.ahajournals.org/cgi/reprint/107/15/e94.pdf through http://circ.ahajournals.org. Accessed on 3/14/07.
University of Illinois Urbana/Champaign, Carle Cancer Center. Patient information on Factor V Leiden. Available online at http://www-admin.med.uiuc.edu/hematology/PtFacV2.htm through http://www-admin.med.uiuc.edu. Accessed on June 2007.
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(Reviewed 2010 August). Factor V Leiden Thrombophilia. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia through http://ghr.nlm.nih.gov. Accessed September 2010.
Shah, S. and Voora, D. (Updated 2010 February 7). Genetics of Venous Thromboembolism. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1797779-overview through http://emedicine.medscape.com. Accessed September 2010.
Hart, K. et. al. (Updated 2010 August). Hypercoagulable States – Thrombophilia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Thrombophilia.html?client_ID=LTD through http://www.arupconsult.com. Accessed September 2010.
(2009 July). The Thrombophilias and Pregnancy. March of Dimes [On-line information]. Available online at http://www.marchofdimes.com/professionals/14332_9264.asp through http://www.marchofdimes.com. Accessed September 2010.
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Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 430-431.
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