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HelpTest ID: APCRV Activated Protein C Resistance V (APCRV), Plasma
Reporting Name
Activated Protein Resistance V, PUseful For
Evaluation of patients with incident or recurrent venous thromboembolism (VTE)
Evaluation of individuals with a family history of VTE
Specimen Type
Plasma Na CitOrdering Guidance
Although this 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 AATHR / Thrombophilia Profile, Plasma and Whole Blood.
Necessary Information
If a priority specimen, mark request form, give reason, and request a call-back.
Specimen Required
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Polypropylene vial
Specimen Volume: 1 mL
Collection Instructions:
1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.
2. Centrifuge, transfer all plasma into a vial, and centrifuge plasma again.
3. Aliquot plasma into a vial leaving 0.25 mL in the bottom of centrifuged vial.
4. Freeze plasma immediately (no longer than 4 hours after collection) at -20° C or, ideally at-40° C or below.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. If priority specimen, mark request form, give reason, and request a call-back.
3. Each coagulation assay requested should have its own vial.
Specimen Minimum Volume
0.5 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Special Instructions
Reference Values
APCRV RATIO
≥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.
Day(s) Performed
Monday through Friday
Test Classification
This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.CPT Code Information
85307
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| APCRV | Activated Protein Resistance V, P | 13590-5 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| APCR | APCRV Ratio | 13590-5 |
| INT55 | Interpretation | 48591-2 |
Clinical Information
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.
Interpretation
An activated protein C (APC) resistance ratio of less than 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.
Clinical Reference
1. Nichols WL, Heit JA. Activated protein C resistance and thrombosis. Mayo Clin Proc. 1996;71(9):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(8):643-650
4. Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA; ACMG Factor V. Leiden Working Group. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med. 2001;3(2):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(11):1304-1318
6. Favaloro EJ and Lippi G. eds. Hemostasis and Thrombosis: Methods and Protocols. 1st ed. Humana Press; 2017
Report Available
1 to 3 daysMethod Name
Optical Clot-Based
Forms
If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.
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