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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 |
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
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.
Cautions
This assay is highly sensitive and specific for inherited activated protein C (APC) resistance, most commonly due to the factor V Leiden mutation, but it 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, lupuslike 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 ensure accuracy of results and interpretation.
The activated protein C resistance ratio (APCRV) assay has greater than 99% sensitivity for detecting the presence of a factor V Leiden mutation. Discrepant results of plasma-based APCRV and DNA-based factor V Leiden testing may occur in recipients of liver or allogeneic hematopoietic stem cell transplants; or due to anticoagulant effects such as excess heparin; direct thrombin inhibitors argatroban (Acova), bivalirudin (Angiomax), or dabigatran (Pradaxa); or direct factor Xa inhibitors rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa); or a sample mix-up. Clinical correlation is suggested. If clinically indicated, consider follow-up repeat APCR testing or direct DNA-based testing for the factor V Leiden (R506Q) mutation (F5DNA / Factor V Leiden [R506Q] Mutation, Blood).
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
Method Description
This assay is performed using the HemosIL Factor V Leiden (APC Resistance V) Kit on the Instrumentation Laboratory ACL TOP instrument. The method uses a modified activated partial thromboplastin time (APTT) test to detect activated protein C (APC) resistance. The plasma specimen is prediluted in factor V-deficient plasma. Then the APTT test is performed by incubating patient plasma with a standardized amount of platelet-like phospholipids and activator of the contact factors of the intrinsic coagulation pathway, followed by recalcification of plasma and measurement of clotting time. The ratio of the APTT test with and without added APC is reported as the APC resistance (or sensitivity) ratio.(Package insert: HemosIL Factor V Leiden [APC Resistance V]. Instrumentation Laboratory Company; Rev 11/2017)
Report Available
1 to 3 daysReject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
NY State Approved
YesMethod Name
Optical Clot-Based
Forms
If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.