Lab Test: Activated Protein C Resistance

Lab Test: Activated Protein C Resistance

Lab Test

Description

Protein C is a natural endogenous protein found in the blood that serves as an anticoagulant.
This is part of the evaluation of patients with coagulation disorders and identifies patients who are deficient in protein C and/or S.
A deficiency in activated protein C would result in an increased risk for clot formation since there is decreased or no inhibitory feedback on the coagulation cascade by protein C.

Reference Range

Protein S: 60%-130% of normal activity
Protein C: 70%-150% of normal activity
Note: Protein C decreases with age and in females. Second generation assays for APC resistance is near 100%. (Dahlback 1995; Samama 1996).

Indications & Uses

Plasma coagulation system is tightly regulated between clot formation (i.e., thrombosis) and clot breakdown (i.e., fibrinolysis). The protein C-protein S system is an important inhibitor of the coagulation cascade and clot formation. Protein C inhibits the activation of co-factors VIII and V and this influence is enhanced by protein S. Congenital deficiencies of these vitamin K-dependent clotting factors may cause spontaneous intravascular thrombosis.
Nearly 50% of hypercoagulable states are caused by the presence of a factor V that is resistant to protein C inhibition.
Protein S activity should be tested alone with protein C because the decreased activity of protein C may the result of decreased protein S.
Both proteins are vitamin K dependent for their functional activation after being made in the liver. They are decreased in patients taking warfarin (Coumadin; Jantoven), as well as those with liver diseases or severe malnutrition. Increased binding of protein S may cause an acquired protein S deficiency and hypercoagulable events may occur.
Measurement of plasma free protein S antigen is performed as the initial testing for protein S deficiency.
If the free protein S antigen level is below the age- and sex-adjusted normal range, quantification for total plasma protein S antigen is indicated.

Clinical Application

Significance of decreased protein C levels:

Inherited deficiency of protein C or protein S: Protein S or C defect may not be recognized until adulthood.
Disseminated intravascular coagulation (DIC), hypercoagulable states, pulmonary emboli, arterial or venous thrombosis: these diseases, when recurrent, may be the result of a protein C or S deficiency.
Vitamin K deficiency: If vitamin K is not available because of malnutrition, biliary disease, or malabsorption, Protein C and S will not be functionally activated in adequate levels. Because several coagulation factors are also vitamin K-dependent, a hypercoagulable event may not occur.
Sickle cell disease: this condition alone does not produce a thrombophilic state.
Autoimmune diseases, inflammation: these proteins may be "used-up" in the inflammatory process.
Warfarin-induced skin necrosis: Occurs in feet, buttocks, thighs, breasts, upper extremities, and genitalia. Begin as maculopapular lesions and progress into bullous hemorrhagic, necrotic lesions. Patients with protein C deficiency are at high risk for warfarin-induced skin necrosis during the initiation of therapy with warfarin (Coumadin; Jantoven). Approximately one third of patients with warfarin-induced skin necrosis have protein C deficiency as is the reason patients with clots present are initiated on parenteral anticoagulation at the same time as warfarin.

Related Tests

Drug-Lab Interactions

Decreased protein C may occur in the postoperative states.
Pregnancy or the use of exogenous sex hormones is associated with decreases in proteins C and S.
The concentration of citrate in the collection tube varies and can affect activity results.
Active clotting states, such as DVT, can lower levels of protein S and C.
Vitamin K inhibitors such as warfarin can decrease levels.

Test Tube Needed

Collect a venous blood sample in a blue-top tube. Fill tube to 90% or near complete capacity.

Procedure

If more than one blood test is to be obtained, draw the blood for proteins C or S second to avoid contamination with tissue thromboplastin that may occur in the first tube.
If only blood for protein C or S is being drawn, draw a red top first (and throw it away) and then draw the blood for this study in a blue top tube.
Place the tube in an ice bath.
Apply pressure to the venipuncture site after procedure.
If the patient is found to be deficient in either protein, encourage the patient's family to be tested as they too may be similarly affected.

Storage and Handling

What To Tell Patient Before & After

References

Bertina RM et al. Mutation in blood coagulation factor V associated with resistance to protein C. Nature 1994;369(6475):64-67. PMID: 8164741
Dahlback B. Resistance to activate protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb Haemost 1995l73:739-42. PMID: 7482395
Dahlback B et al. Factor V and protein S as cofactors to activated protein C. Haematologica 1997;82(1):91-95. PMID: 9107093
LaGow B et al., eds. PDR Lab Advisor. A Comprehensive Point-of-Care Guide for Over 600 Lab Tests. First ed. Montvale, NJ: Thomson PDR; 2007.
Pagana K, Pagana TJ eds. Mosby's Manual of Diagnostic and Laboratory Tests. 5^th Ed. St. Louis, Missouri. 2014.
Samama MM et al. Diagnosis and clinical characteristics of inherited activated protein C resistance.
Haemostatsis 1996;26 suppl 4:315-30. PMID: 8979137
Pruller F et al. Activated protein C resistance and factor V Leiden. N Engl J Med 2014;371(7):685-6. PMID: 25119624

MESH Terms & Keywords
Activated Protein C Resistance, Hypercoaguable Lab Tests

MESH Terms & Keywords