Test Id : APCRV
Activated Protein C Resistance V (APCRV), Plasma
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
Method Name
A short description of the method used to perform the test
Optical Clot-Based
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Activated Protein CV deficient
APCRV (Activated Protein C Resistance V)
TEST
Specimen Type
Describes the specimen type validated for testing
Plasma Na Cit
Ordering 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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
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 degrees C or, ideally at-40 degrees C or below.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. Each coagulation assay requested should have its own vial.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.5 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
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
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.
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.
APCRV RATIO
> 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.
Interpretation
Provides information to assist in interpretation of the test results
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
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 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
Recommendations for in-depth reading of a clinical nature
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
Describes how the test is performed and provides a method-specific reference
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, Bedford, MA, Rev 10/2012)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Monday through Friday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
85307
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| APCRV | Activated Protein Resistance V, P | 13590-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| APCR | APCRV Ratio | 13590-5 |
| INT55 | Interpretation | 48591-2 |