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Test Code LAB2531 Activated Protein C Resistance V (APCRV), Plasma

Additional Codes

Test Name in EPIC EPIC Test Code Mnemonic Mayo Test ID
ACTIVATED PROTEIN C
RESISTANCE V, P
LAB2531 APRVP APCRV

 

Reporting Name

Activated Protein Resistance V, P

Useful For

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

 

Evaluation of individuals with a family history of VTE

Method Name

Clot-Based Assay

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Plasma Na Cit


Advisory Information


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 THRMP / Thrombophilia Profile.



Necessary Information


If priority specimen, mark request form, give reason, and request a call-back.



Specimen Required


See Coagulation Studies in Special Instructions.

 

Specimen Type: Platelet-poor plasma

Collection Container/Tube: Light-blue top (citrate)

Submission Container/Tube: Polypropylene vial

Specimen Volume: 1 mL

Collection Instructions:

1. Spin down, remove plasma

2. Spin plasma again; remove plasma aliquot without disturbing bottom 0.5 mL

3. Freeze specimen aliquot immediately at or below -40° C, if possible but no longer than 4 hours after collection

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
Plasma Na Cit Frozen 14 days

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

Mild OK; Gross reject

Other

NA

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) and Time(s) Performed

Monday through Friday

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

Analytic Time

1 day

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 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 insure 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.

Method Description

This assay is performed using the HemosIL Factor V Leiden (APC Resistance V) Kit on the 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, Bedford, MA, Rev 10/2012)

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.

Specimen Retention Time

7 days

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.

Test Classification

This test has been cleared or approved by the U.S. 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.

Forms

If not ordering electronically, complete, print, and send a Coagulation Test Request Form (T753) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/coagulation-test-request-form.pdf)