Coagulation
Hereditary thrombophilia / hypercoagulopathies
Activated protein C resistance / Factor V Leiden
Author: Jeremy C. Parsons, M.D.
Last author update: 1 June 2012
Last staff update: 10 September 2020
Copyright: 2002-2025, PathologyOutlines.com, Inc.
PubMed Search: Activated protein C resistance / Factor V Leiden
Table of Contents
Definition / general | Etiology | Diagrams / tables | Laboratory | Case reports | Treatment | Additional referencesCite this page: Parsons JC. Activated protein C resistance / Factor V Leiden. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationactivatedproteinC.html. Accessed January 10th, 2025.
Definition / general
- Most common hereditary predisposition to venous thrombosis (20% of first episodes of thrombosis, 50% of familial thrombosis)
- Normally, activated protein C degrades activated factors V and VIII by cleaving specific arginine residues
- Almost all patients with activated protein C resistance have Factor V Leiden mutation that causes resistance to degradation by activated protein C
- Approximately 64% of people with venous thrombosis have activated protein C deficiency
- Does not appear to reduce life expectancy
- Acquired forms of activated protein C deficiency can lead to elevated factor VIII levels
Etiology
- Factor V Leiden mutations:
- 95% with activated protein C resistance have point mutation at an arginine cleavage site (Arg506Gln, 1691 G to A) called R506Q or Factor V Leiden
- Mutation causes delayed inactivation by activated protein C, prolonging its life span and procoagulant activity
- 3 - 5% frequency in heterozygous form in general white population
- Rare in African blacks and Asians
- Heterozygotes have 5 - 10x increased risk for venous thrombosis
- Homozygotes have 80x increased risk for venous thrombosis; risk occurs later in life
- Homozygosity or heterozygosity without symptoms may not require treatment
- Presence of second risk factor (genetic or acquired) is often necessary to produce thrombosis
- Acquired risk factors are smoking, malignancy, trauma, surgery, oral contraceptive use, estrogen replacement therapy, antiphospholipid antibody, heterozygosity for prothrombin G20210A, elevated serum homocysteine
- Other low frequency factor V mutations, which have unclear association with venous thrombosis:
- Factor V Hong Kong (Arg306Gly)
- HR2 haplotype with mutation 4070A to G (His199Arg) in exon 13 of Factor V gene (associated with other polymorphisms)
Diagrams / tables
Images hosted on other servers:
Protein C pathway
Laboratory
- Testing recommended if venous thromboemboli occur with these features:
- Recurrent
- Before age 50 years
- Unprovoked at any age
- At unusual anatomic sites (cerebral, mesenteric, portal or hepatic veins)
- In patient with first degree relative with venous thromboemboli before age 50 years
- Related to pregnancy or estrogen use or unexplained pregnancy loss in second or third trimesters
- May be recommended in family members (with family history), female family members who are pregnant or considering oral contraceptives
- Testing NOT recommended:
- General population screen
- Routine test during pregnancy
- Routine test before or during oral contraceptive use or hormone replacement therapy in patients without a family history of thrombosis
- As newborn initial test
- As initial test in patients with arterial thrombotic events
Case reports
- 51 year old woman with heterozygous factor V Leiden and dural sinus thrombosis (Arch Pathol Lab Med 2003;127:1359)
Treatment
- Treat venous thromboemboli similarly regardless of the presence of factor V Leiden
