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/VTE episodes, 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 and prothrombin are coagulation factors, two of a group of proteins produced by the liver that are essential for proper blood clot formation. When a body tissue or blood vessel wall is injured, a process called hemostasis begins to form a plug at the injury site to help stop the bleeding. Cell fragments called platelets adhere to and aggregate at the injury site, and a coagulation cascade is initiated to sequentially activate coagulation factors. As the process progresses, thrombin converts fibrinogen into fibrin threads that crosslink to form a fibrin net. The fibrin net adheres to the injury site along with the platelets and forms a stable blood clot. This barrier prevents additional blood loss and remains in place until the injured area has healed.
There must be an adequate number of platelets and 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, dysfunctional, or too much of the factors can lead to bleeding or thrombosis.
Factor V Leiden and prothrombin 20210 are produced by genetic mutations that lead to the production of altered factor V protein and increased amount of prothrombin protein, respectively. They are associated with an increased risk of inappropriate clotting (thrombosis). They are independent mutations that are tested separately, but the tests are often performed at the same time as part of the investigation of a thrombotic episode in someone who is suspected of having an inherited risk factor for a clotting (hypercoagulable) disorder. The testing of each is intended to identify whether or not the specific mutation is present and to determine whether the person has one (heterozygous) or two (homozygous) copies of that mutation.
Factor V Leiden is a variant form of factor V associated with a genetic point mutation. The altered protein produced as a result of this mutation activates normally during clotting, but it resists being degraded by activated protein C (APC) during coagulation. APC helps to regulate and slow coagulation as a balance check. Resistance to its actions leads to prolonged factor V activity and thus to an increased risk of venous thrombosis and venous thromboembolism (VTE).
Factor V Leiden mutation is the most common inherited predisposition to abnormal clotting in the United States. Its prevalence is about 5% of the Caucasian population. A person with a factor V Leiden mutation may be heterozygous or, more rarely, homozygous. Those who are heterozygous have a 3 to 8 fold greater risk of developing a VTE than those who don't carry the mutation, while those who are homozygous have a 50 to 80 fold increased risk of thrombosis.
Prothrombin (PT) 20210 is a variant form of prothrombin gene, also caused by a genetic point mutation. PT 20210 is also associated with an increased risk of VTE.
Someone 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; 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.
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
(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.
Spence, R. et. al. (Updated 2010 January 12). Hemostatic Disorders, Nonplatelet eMedicine. [On-line information]. Available online at http://emedicine.medscape.com/article/210467-overview through http://www.nlm.nih.gov. Accessed September 2010.
Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 430-431.
Wu, A. (© 2006). Tietz Clinical Guide to Laboratory Tests, 4th Edition: Saunders Elsevier, St. Louis, MO. Pp 48-49.
Centers for Disease Control and Prevention. Public Health Genomics, HUGENet Case study. Available online at http://www.cdc.gov/genomics/hugenet/CaseStudy/FVL/FVLview.htm through http://www.cdc.gov. Accessed January 2011.
Netwellness.org. Bleeding and Clotting Disorders. The Genetics of Thrombosis. Available online at http://www.netwellness.org/healthtopics/clotting/genthromb.cfm through http://www.netwellness.org. Accessed January 2011.
Sources Used in Previous Reviews
Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].
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.
Chapter 132 Thrombotic Disorders, General. The Merck Manual of Diagnosis and Therapy, Section 11. Hematology And Oncology [Online information]. Available online at http://www.merck.com/pubs/mmanual/section11/chapter132/132a.htm through http://www.merck.com.
Laposata, M. & Vancott, E. (2000 January). How to work up hypercoagulability. CAP Today, In the News [On-line Coagulation Case Study]. Available online at http://www.cap.org/CAPToday/casestudy/coag5.html through http://www.cap.org.
Factor V Leiden. 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/PtFacV2.htm through http://www-admin.med.uiuc.edu.
Ronald C. McGlennen, R. and Key, N. Clinical and Laboratory Management of the Prothrombin G20210A Mutation. College of American Pathologists, Practicing Pathology. Available online through http://www.cap.org.
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.
Menta, S. (1999 Spring). The Coagulation Cascade. Physiology Disorders Evaluation, College of Medicine, Univ of Florida [On-line information]. Available online at http://www.medinfo.ufl.edu/year2/coag/title.html through http://www.medinfo.ufl.edu.
Bauer, K. (2001). The Thrombophilias: Well-Defined Risk Factors with Uncertain Therapeutic Implications. Ann Intern Med. 2001;135:367-373 [Journal]. Available online through http://www.annals.org.
DeLoughery, T. (1999 March 15). Tests of Hemostasis and Thrombosis. OHSU [Online student handout]. Available online at http://www.ohsu.edu/som-hemonc/handouts/deloughery/printtest.html through http://www.ohsu.edu.
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 .
Kujovich, J. (2006 July 25). Prothrombin Thrombophilia. GENEReviews [On-line information]. Available online through http://www.genetests.org. Accessed on 3/16/07.
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.
McPherson R, Pincus M, eds, (2007) Henry's Clinical Diagnosis and Management by Laboratory Methods, 21st edition, Saunders Elsevier.