Lab Test: Activated Protein C Resistance
- Protein C is a natural endogenous protein found in the blood that serves as an anticoagulant.
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.
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).
- 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.
- 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.
- Activated Partial Thromboplastin Time (aPTT)
- Antithrombin levels or function
- Disseminated Intravascular Coagulation (DIC) Screening.
- Factor V Leiden Mutation
- 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.
clotting states, such as DVT, can lower levels of protein S and C.
- Vitamin K inhibitors such as warfarin can decrease levels.
- Collect a venous blood sample in a blue-top tube. Fill tube to 90% or near complete capacity.
- 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.
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.
- 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. 5th Ed. St. Louis, Missouri. 2014.
MM et al. Diagnosis and clinical
characteristics of inherited activated protein C resistance.
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
Indications & Uses
Significance of decreased protein C levels:
Test Tube Needed
MESH Terms & Keywords