Test Catalog

Interpretive Handbook

Test 81967 :
Activated Protein C Resistance V (APCRV), Plasma

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Protein C, a part of the natural anticoagulant system, is a vitamin K-dependent protein zymogen (molecular weight=62,000 da) that is synthesized in the liver and circulates at a plasma concentration of approximately 5 mcg/mL. Protein C is activated to activated protein C (APC) via proteolytic cleavage by thrombin bound to thrombomodulin, an endothelial cell surface membrane protein. APC downregulates the procoagulant system by proteolytically inactivating procoagulant factors Va and VIIIa. Protein S, another vitamin K-dependent coagulation protein, catalyzes APC inactivation of factors Va and VIIIa. APC interacts with and proteolyses factors V/Va and VIII/VIIIa at specific APC binding and cleavage sites, respectively. Resistance to activated protein C (APC resistance) is a term used to describe abnormal resistance of human plasma to the anticoagulant effects of human APC. APC resistance is characterized by a reduced anticoagulant response of patient plasma after adding a standard amount of APC. For this assay, the activated partial thromboplastin time clotting test fails to prolong significantly after the addition of APC.


The vast majority of individuals with familial APC resistance have a specific point mutation in the procoagulant factor V gene (1691G-A, factor V Leiden) encoding for a glutamine (Q) substitution for arginine (R)-506 in the heavy chain of factor V (factor V R506Q). This amino acid change alters an APC cleavage site on factor V such that factor V/Va is partially resistant to inactivation by APC. The carrier frequency for the factor V Leiden mutation varies depending on the population. Approximately 5% of asymptomatic white Americans of non-Hispanic ancestry are heterozygous carriers, while the carrier frequency among African Americans, Asian Americans, and Native Americans is less than 1%, and the carrier frequency for Hispanics is intermediate (2.5%). The carrier frequency can be especially high (up to 14%) among whites of Northern European or Scandinavian ancestry. Homozygosity for factor V Leiden is much less common, but may confer a substantially increased risk for thrombosis. The degree of abnormality of the APC-resistance assay correlates with heterozygosity or homozygosity for the factor V Leiden mutation; homozygous carriers have a very low APC-resistance ratio (eg, 1.1-1.4), while the ratio for heterozygous carriers is usually 1.5 to 1.8.

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of patients with incident or recurrent venous thromboembolism (VTE)


Evaluation of individuals with a family history of VTE

Interpretation Provides information to assist in interpretation of the test results

An activated protein C (APC) resistance ratio of <2.3 suggests abnormal resistance to APC of hereditary origin.


If the APC resistance test is abnormal, DNA-based testing for the factor V Leiden mutation (F5DNA / Factor V Leiden [R506Q] Mutation, Blood) may be helpful in confirming or excluding hereditary APC-resistance.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay is highly sensitive and specific for inherited activated protein C (APC) resistance, most commonly due to the factor V Leiden mutation, but will not detect patients with acquired APC resistance. Persons with acquired APC resistance are at similar risk for venous thromboembolism.

Preanalytical conditions of the patient and the blood specimen are extremely important for reliable performance and interpretation of testing for APC-resistance. Plasmas demonstrating prolongation of clotting times (prothrombin time, activated partial thromboplastin time) for reasons other than anticoagulant effects (eg, lupus-like anticoagulants or specific coagulation factor inhibitors) generally cannot be reliably tested for the presence or absence of APC resistance. Proper preparation of the blood (plasma) specimen is extremely important to help insure accuracy of results and interpretation.


Although the APC-resistance assay can be performed in the absence of other coagulation tests and clinical information, it is most reliably performed as part of a consultative coagulation test panel with interpretive reporting (including appropriate testing of the same specimen to evaluate for the presence or absence of coagulation abnormalities or conditions that may affect interpretation of the APC-resistance assay). This test is included among a panel of tests designated THRMP / Thrombophilia Profile.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


> or =2.3

Pediatric reference range has neither been established nor is available in scientific literature. The adult reference range likely would be applicable to children older than 6 months.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Nichols WL, Heit JA: Activated protein C resistance and thrombosis. Mayo Clin Proc 1996;71:897-898

2. Dahlback B: Resistance to activated protein C as risk factor for thrombosis: molecular mechanisms, laboratory investigation, and clinical management. Semin Hematol 1997;34(3):217-234

3. Rodeghiero F, Tosetto A: Activated protein C resistance and Factor V Leiden mutation are independent risk factors for venous thromboembolism. Ann Intern Med 1999;130:643-650

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 Pathol Lab Med 2002;126:1304-1318