Differentiating congenital type I protein C deficiency from type II deficiency
Evaluating the significance of decreased functional protein C, especially when decreased protein C activity might be congenital rather than acquired (eg, due to oral anticoagulant effect, vitamin K deficiency, liver disease, or intravascular coagulation and fibrinolysis/disseminated intravascular coagulation)
This test is not useful for predicting a thrombotic event.
Enzyme-Linked Immunosorbent Assay (ELISA)
Protein C Immunologic
Plasma Na Cit
Coagulation testing is highly complex, often requiring the performance of multiple assays and correlation with clinical information. For that reason, consider ordering AATHR / Thrombophilia Profile, Plasma and Whole Blood.
Testing of protein C functional activity (CFX / Protein C Activity, Plasma) is recommended for initial laboratory evaluation of patients suspected of having congenital protein C deficiency (personal or family history of thrombotic diathesis).
If the patient is being treated with Coumadin (warfarin), this should be noted as Coumadin will lower protein C.
Specimen Type: Platelet-poor plasma
Patient Preparation: Fasting preferred
Collection Container/Tube: Light-blue top (3.2% sodium citrate)
Submission Container/Tube: Plastic vial (polypropylene preferred)
Specimen Volume: 1 mL
Specimen Stability Information: Frozen 2 years
Collection Instructions:
1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.
2. Centrifuge, transfer all plasma into a plastic vial, and centrifuge plasma again.
3. Aliquot plasma into a plastic vial leaving 0.25 mL in the bottom of centrifuged vial.
4. Freeze plasma immediately (no longer than 4 hours after collection) at -20 degrees C or ideally, at or below -40 degrees C.
Additional Information:
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.
If not ordering electronically, complete, print, and send a Coagulation Test Request (T753) with the specimen.
0.5 mL
Gross hemolysis | Reject |
Gross lipemia | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Plasma Na Cit | Frozen |
Differentiating congenital type I protein C deficiency from type II deficiency
Evaluating the significance of decreased functional protein C, especially when decreased protein C activity might be congenital rather than acquired (eg, due to oral anticoagulant effect, vitamin K deficiency, liver disease, or intravascular coagulation and fibrinolysis/disseminated intravascular coagulation)
This test is not useful for predicting a thrombotic event.
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 type 1 (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 the patient 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.
The 2 types of hereditary heterozygous protein C deficiencies that are recognized are:
-Type I (concordantly decreased protein C function and antigen)
-Type II (decreased protein C function with normal antigen)
Acquired deficiency of protein C may occur in association with:
-Vitamin K deficiency
-Oral anticoagulation with Coumadin (warfarin) compounds
-Liver disease
-Intravascular coagulation and fibrinolysis/disseminated intravascular coagulation
Adults: 72%-160%
Normal, full-term newborn infants or healthy premature infants may have decreased levels of protein C antigen (15%-50%), which may not reach adult levels until later in childhood or early adolescence.*
*See Pediatric Hemostasis References section in Coagulation Guidelines for Specimen Handling and Processing.
Values less than 70% to 75% may represent a congenital deficiency state, if acquired deficiencies can be excluded.
Protein C antigen and activities generally are undetectable in individuals with severe, homozygous protein C deficiency.
Acquired protein C deficiency is of uncertain clinical hemostatic significance.
The clinical significance of increased protein C is unknown.
No significant cautionary statements
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. Edinburgh, 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(3):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 Haemeostasis. J Pediatr. 1989;114(4 Pt 1):528-534
4. Miletrich J, Sherman L, Broze G Jr. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med. 1987;317(16):991-996
5. Cooper PC, Pavlova A, Moore GW, Hickey KP, Marlar 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(2):271-277
Protein C antigen is quantitated by enzyme-linked immunoassay using monospecific antibody. The assay is performed using the REAADS PCAg kit on a Janus G3 integrated system, which includes a BioTek microplate reader.(Package insert: REAADS Protein C Antigen Test Kit. Corgenix, Inc; 08/2015)
Monday through Friday
This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.
85302
Test Id | Test Order Name | Order LOINC Value |
---|---|---|
PCAG | Protein C Ag, P | 27820-0 |
Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
---|---|---|
9127 | Protein C Ag, P | 27820-0 |