Protein C Activity, Plasma
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
As an initial test for evaluating patients suspected of having congenital protein C deficiency, including those with personal or family histories of thrombotic events
Because coagulation testing and its interpretation is complex, Mayo Medical Laboratories suggests ordering THRMP / Thrombophilia Profile.
Detecting and confirming congenital Type I and Type II protein C deficiencies, detecting and confirming congenital homozygous protein C deficiency, and 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.)
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Amidolysis of Chromogenic Substrate
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Protein C Activity, P
Functional Protein C
Protein C, Functional, Plasma
Protein C, Functional, Plasma
Specimen Type Describes the specimen type needed for testing
Plasma Na Cit
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
See Coagulation Studies in Special Instructions.
Specimen Type: Platelet-poor plasma
Collection Container/Tube: Light-blue top (citrate)
Submission Container/Tube: Plastic vial
Specimen Volume: 1 mL
2. Spin down, remove plasma, and spin plasma again.
3. Freeze specimen immediately at < or =-40 degrees C, if possible.
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.
3. If the patient is being treated with Coumadin, this should be noted. Coumadin will lower protein C.
4. Heparin > or =4 U/mL may interfere with this assay.
5. Lipemic specimen may be rejected.
6. Coagulation testing is highly complex, often requiring the performance of multiple assays and correlation with clinical information. For that reason, we suggest ordering THRMP / Thrombophilia Profile.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Mild OK; Gross reject
Mild OK; Gross reject
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Plasma Na Cit||Frozen||14 days|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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.
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
-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.
Normal, full-term newborn infants or healthy premature infants may have decreased levels of protein C activity (15%-50%), which may not reach adult levels until later in childhood or early adolescence.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Values <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) >4 U/mL
-Heparin (low-molecular-weight) >2 U/mL
-Hemoglobin >500 mg/dL
-Bilirubin >21 mg/dL
-Triglycerides >890 mg/dL
Heparin therapy may temporarily decrease plasma protein C activity into the abnormal range.
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 Provides recommendations for further in-depth reading of a clinical nature
1. Mannucci PM, Owen WG: Basic and clinical aspects of proteins C and S. In Haemostasis and Thrombosis. Second edition. Edited by AL Bloom, DP Thomas. Edinburgh, Churchill Livingstone, 1987, pp 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
Method Description Describes how the test is performed and provides a method-specific reference
This Protein C activity assay is performed using the HemosIL Protein C kit on the Beckman Coulter ACL TOP. Protein C in plasma is activated by a specific enzyme (Protein C activator) from copperhead snake venom (Agkistrodon contortrix contortrix). The amount of activated protein C is determined by the rate of hydrolysis of the chromogenic substrate, S-2366 (pyroGlu Pro-Arg-pNA-HCL). The pNA release is measured kinetically at 405 nm and is directly proportional to the protein C level in the plasma.(Package insert: HemosIL Protein C, Instrumentation Laboratory, Bedford, MA, 12/2008)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|CFX||Protein C Activity, P||27818-4|