Activated Protein C Resistance V (APCRV), Plasma

CPT CODE:

USEFUL FOR:

Evaluation of patients with incident or recurrent venous thromboembolism
Evaluation of individuals with a family history of venous thromboembolism
Evaluation of women with recurrent miscarriage or complications ofpregnancy (eg, severe preeclampsia, abruptio placentae, intrauterine growth restriction, and stillbirth)
Possibly useful for evaluation of individuals with a history of arterialthrombosis (eg, stroke, acute myocardial infarction, or other acute coronary syndromes), especially among young patients (ie, <50 years) or patients with no other risk factors for arthrosclerosis

SPECIMEN REQUIRED:

See "Coagulation Studies" in "Special Instructions."      1. Draw blood in a light blue-top (citrate) tube(s). Spin down, remove      plasma, spin plasma again, and place 1 mL of platelet-poor plasma      in plastic vial. (Glass vial is not acceptable.)     Note:           Double-centrifuged specimens are critical for accurate                           results as platelet contamination may cause spurious                           results.2. Freeze specimen immediately at < or = -40 degrees C, if possible.3. Send specimen frozen.4. If priority specimen, mark requisition, give reason, and request      a call-back.Note:      1. Each coagulation assay requested should have its own                       vial.             2. If ordering electronically, no form is required with the specimen.                      If not ordering electronically, please complete and submit a                      "Coagulation Request Form" (Supply T237) with the specimen.

TRANSPORT TEMPERATURE:

Frozen\Refrig NO\Ambient NO

CLINICAL INFORMATION:

Protein C is a vitamin K-dependent protein zymogen (MW = 62,000 da)that is synthesized in the liver and circulates at a plasma concentrationof approximately 5 ug/mL. Protein C is part of the natural anticoagulantsystem. Protein C is activated to activated protein C (APC) viaproteolytic cleavage by thrombin bound to thrombomodulin, anendothelial cell surface membrane protein. APC down-regulates the procoagulant system by proteolytically inactivating procoagulantfactors Va and VIIIa. Protein S, another vitamin K-dependent coagulationprotein, catalyzes APC inactivation of factors Va and VIIIa. APC interacts with and proteolyses factors V/Va and VIII/VIIIa at specificAPC 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 anticoagulanteffects 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 (APTT) clotting test fails to prolong significantly after the addition of APC.
The 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 amongAfrican Americans, Asian Americans, and Native Americans is <1%,and the carrier frequency for Hispanics is intermediate (2.5%). Thecarrier 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.

CLINICAL INTERPRETATION:

An APC-R ratio of <2.3 suggests abnormal resistance to APC of hereditary origin.
DNA-based testing for the factor V Leiden mutation (#81419, "Factor V Leiden [R506Q] Mutation, Blood”) may be helpful in confirming or excluding hereditary APC-resistance, after initial screening with the APC-resistance test.
This assay is highly sensitive and specific for inherited 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.

REFERENCE VALUES:

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 >6 months.

REPORTABLE RANGE

1.0-10.0