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Test Catalog

Test ID: CFX    
Protein C Activity, Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

As an initial test for evaluating patients suspected of having congenital protein C deficiency, including those with personal or family histories of thrombotic events

 

Detecting and confirming congenital type I and type II protein C deficiencies

 

Detecting and confirming congenital homozygous protein C deficiency

 

Identifying decreased functional protein C of acquired origin (eg, due to oral anticoagulant effect, vitamin K deficiency, liver disease, intravascular coagulation and fibrinolysis/disseminated intravascular coagulation)

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Physiology:

Protein C is a vitamin K-dependent anticoagulant proenzyme. It is synthesized in the liver and circulates in the plasma. The biological half-life of plasma protein C is approximately 6 to 10 hours, similar to the relatively short half-life of coagulation factor VII.

 

Protein C is activated by thrombin, in the presence of an endothelial cell cofactor (thrombomodulin), to form the active enzyme activated protein C (APC). APC functions as an anticoagulant by proteolytically inactivating the activated forms of coagulation factors V and VIII (factors Va and VIIIa). APC also enhances fibrinolysis by inactivating plasminogen activator inhibitor (PAI-1).

 

Expression of the anticoagulant activity of APC is enhanced by a cofactor, protein S, another vitamin K-dependent plasma protein.

 

Pathophysiology:

Congenital homozygous protein C deficiency results in a severe thrombotic diathesis, evident in the neonatal period and resembling purpura fulminans.

 

Congenital heterozygous protein C deficiency may predispose to thrombotic events, primarily venous thromboembolism; arterial thrombosis (stroke, myocardial infarction, etc.) may occur. Some individuals with hereditary heterozygous protein C deficiency may have no personal or family history of thrombosis and may or may not be at increased risk. Congenital heterozygous protein C may predispose to development of coumarin-associated skin necrosis. Skin necrosis has occurred during the initiation of oral anticoagulant therapy.

 

Two types of hereditary heterozygous protein C deficiency are recognized:

-Type I (concordantly decreased protein C function and antigen)

-Type II (decreased protein C function with normal antigen level)

 

Acquired deficiencies of protein C may occur in association with:

-Vitamin K deficiency

-Oral anticoagulation with coumarin compounds

-Liver disease

-Intravascular coagulation and fibrinolysis/disseminated intravascular coagulation (ICF/DIC)

 

The clinical hemostatic significance of acquired protein C deficiency is uncertain.

 

Assay of protein C functional activity is recommended for the initial laboratory evaluation of patients suspected of having congenital protein C deficiency (personal or family history of thrombotic diathesis), rather than assay of protein C antigen (PCAG / Protein C Antigen, Plasma).

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.

70-150%

Interpretation Provides information to assist in interpretation of the test results

Values below 60% to 70% may represent a congenital deficiency state, if acquired deficiencies can be excluded.

 

Protein C activity (and antigen) is generally undetectable in individuals with severe, homozygous protein C deficiency.

 

Oral anticoagulant therapy (warfarin, Coumadin) decreases protein C activity, compromising the ability to distinguish between congenital and acquired protein C deficiency. Concomitant measurement of the activity of coagulation factor VII (or factor X) may aid in differentiating congenital deficiency state from acquired protein C deficiency due to oral anticoagulant effect, but the ratio of the activities of protein C:factor VII (or factor X) has not been demonstrated to provide certainty about  this distinction.

 

The clinical significance of acquired protein C deficiency and of increased protein C is unknown.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Protein C activity result may be affected by:

-Heparin (unfractionated) > or =2 U/mL

-Heparin (low molecular weight) >2 U/mL

-Hemoglobin >500 mg/dL

-Bilirubin >21 mg/dL

-Triglycerides >890 mg/dL

 

Lipemia may interfere with functional protein C assay. Blood specimens for protein C functional assay should be drawn in the fasting state, if possible.

 

Protein C functional assay using a venom activator and a chromogenic peptide substrate has the potential of not detecting certain congenital protein C variants that might be detectable using clot-based assay of protein C function.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Mannucci PM, Owen WG: Basic and clinical aspects of proteins C and S. In: Bloom AL, Thomas DP, eds. Haemostasis and Thrombosis. 2nd ed. Churchill Livingstone; 1987:452-464

2. Marlar RA, Mastovich S: Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment. Blood Coagul Fibrinolysis. 1990;1:319-330

3. Marlar RA, Montgomery RR, Broekmans AW: Diagnosis and treatment of homozygous protein C deficiency. Report of the Working Party on Homozygous Protein C Deficiency of the Subcommittee on Protein C and Protein S, International Committee on Thrombosis and Haemostasis. J Pediatr. 1989;114:528-534

4. Miletich J, Sherman L, Broze G Jr: Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med. 1987;317:991-996

5. Pabinger I, Allaart CF, Hermans J, et al: Hereditary protein C-deficiency: laboratory values in transmitters and guidelines for the diagnostic procedure. Report on a study of the SSC Subcommittee on Protein C and Protein S. Protein C Transmitter Study Group. Thromb Haemost. 1992;68:470-474

6. Cooper PC, Pavlova A, Moore GA, Hickey KP, Arlar RA: Recommendations for clinical laboratory testing for protein C deficiency, for the subcommittee on plasma coagulation inhibitors of the ISTH. J Thromb Haemost. 2020;18:271-277

7. Baron JM, Johnson SM, Ledford-Kraemer MR, Hayward CP, Meijer P, Van Cott EM. Protein C assay performance: an analysis of North American specialized coagulation laboratory association proficiency testing results. Am J Clin Pathol. 2012 Jun;137(6):909-15. doi: 10.1309/AJCP8MWU4QSTCLPU.

8. Roshan TM, Stein N, Jiang XY. Comparison of clot-based and chromogenic assay for the determination of protein c activity. Blood Coagul Fibrinolysis. 2019 Jun;30(4):156-160. doi: 10.1097/MBC.0000000000000806

Special Instructions Library of PDFs including pertinent information and forms related to the test