Merck Manual

Please confirm that you are a health care professional

honeypot link

Factor V Resistance to Activated Protein C (APC)

By

Michael B. Streiff

, MD, Johns Hopkins University School of Medicine

Reviewed/Revised Aug 2023
View PATIENT EDUCATION
Topic Resources

Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis.

Activated protein C (APC), in complex with protein S, degrades coagulation factors Va and VIIIa, thus inhibiting coagulation (see figure ). Any of several mutations to factor V make it resistant to inactivation by APC, increasing the tendency for thrombosis.

Factor V Leiden is the most common of these mutations. Homozygous mutations increase the risk of thrombosis more than do heterozygous mutations.

Pathways in Blood Coagulation

Pathways in Blood Coagulation

General references

Diagnosis of Factor V Resistance to APC

  • Plasma coagulation assay

Diagnosis is based on

  • The activated protein C resistance assay

  • Genetic mutation analysis of the factor V gene using DNA-based assays

The activated protein C resistance assay is a screening test for the presence of factor V Leiden. Activated protein C is added to a 5-fold dilution of patient plasma, and the coagulation time is measured. In patients with homozygous or heterozygous factor V Leiden resistance, the prolongation of the clotting time is significantly reduced because their factor V is resistant to cleavage by activated protein C.

Confirmation of factor V Leiden is then done by DNA-based testing for the mutation.

Treatment of Factor V Resistance to APC

  • Anticoagulation

Direct oral anticoagulants are at least as effective as warfarin for the treatment of venous thromboembolism in patients with thrombophilia including factor V Leiden (1 Treatment reference Mutations of factor V make it resistant to its normal cleavage and inactivation by activated protein C, and they also predispose to venous thrombosis. (See also Overview of Thrombotic Disorders... read more ).

Treatment reference

  • 1. Campello E, Spiezia L, Simion C, et al. Direct Oral Anticoagulants in Patients With Inherited Thrombophilia and Venous Thromboembolism: A Prospective Cohort Study. J Am Heart Assoc 2020;9(23):e018917. doi:10.1161/JAHA.120.018917

Drugs Mentioned In This Article

Drug Name Select Trade
Coumadin, Jantoven
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
quiz link

Test your knowledge

Take a Quiz! 
iOS ANDROID
iOS ANDROID
iOS ANDROID
TOP