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Test Code APCRR Activated Protein C Resistance V, with Reflex to Factor V Leiden, Blood and Plasma

Useful For

Evaluating patients with incident or recurrent venous thromboembolism (VTE)

 

Evaluating individuals with a family history of VTE

Profile Information

Test ID Reporting Name Available Separately Always Performed
APCRV Activated Protein Resistance V, P Yes Yes
SC018 Whole Blood No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
F5DNA Factor V Leiden (R506Q) Mutation, B Yes No
F5DNI APCRV/F5DNA Summary Interpretation No No

Method Name

Optical Clot-Based

Reporting Name

APCRV, w/Reflex, P

Specimen Type

Plasma Na Cit
Whole blood


Necessary Information


 



Specimen Required


Blood and plasma are required.

 

Patient Preparation: Fasting preferred

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Yellow top (ACD) or light-blue top (3.2% sodium citrate)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

 

Specimen Type: Platelet-poor plasma

Collection Container/Tube: Light-blue top (3.2% sodium citrate)

Submission Container/Tube: Plastic vial, polypropylene preferred

Specimen Volume: 1 mL

Collection Instructions:

1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.

2. Within 4 hours of collection, centrifuge, transfer all plasma into a plastic vial, and centrifuge plasma again.

3. Aliquot plasma into separate plastic vial leaving 0.25 mL in the bottom of centrifuged vial.

4. Freeze plasma aliquot immediately 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. Each coagulation assay requested should have its own vial.


Specimen Minimum Volume

Plasma: 0.5 mL; Whole blood: 3 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma Na Cit Frozen 14 days
Whole blood Ambient (preferred) 14 days
  Frozen  14 days
  Refrigerated  14 days

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

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 proteolyzes 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 fails to prolong significantly after the addition of APC.

 

The vast majority of individuals with familial APC resistance have a specific alteration in the procoagulant factor V gene (F5) encoding for a p.Arg534Gln substitution in the heavy chain of factor V (formerly R506Q). This glutamine to arginine 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 variant varies depending on the population. Approximately 5% of asymptomatic White Americans of non-Hispanic ancestry are heterozygous carriers. In contrast, 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 White individuals 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 variant; 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

ACTIVATED PROTEIN C RESISTANCE V 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

Report Available

4 to 7 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

CPT Code Information

85307

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Coagulation Patient Information (T675)

3. If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.

Test Classification

See Individual Test IDs