Test ID: S_FX
Protein S Activity, Plasma
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Second-order testing for diagnosis of congenital or acquired protein S deficiency for example, as an adjunct to initial testing based on results of protein S antigen assay (free protein S antigen, with or without total protein S antigen assay)
Evaluating patients with a history of venous thromboembolism
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
Method Name A short description of the method used to perform the test
Clot-Based End point
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Protein S Activity, Plasma
Specimen Type Describes the specimen type needed for testing
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
Collection Instructions:
1. Spin down, remove plasma, and spin plasma again.
2. Freeze specimen immediately at < or =-40 degrees C, if possible.
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.
3. Patient must not be receiving heparin or Coumadin.
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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Plasma Na Cit | Frozen | 14 days |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Protein S is a vitamin K-dependent plasma glycoprotein synthesized predominantly within the liver. Protein S is also synthesized in endothelial cells and present in platelets. As a part of the plasma anticoagulant system, protein S acts as a necessary cofactor to activated protein C (APC) in the proteolytic inactivation of procoagulant factors Va and VIIIa. About 60% of the total plasma protein S antigen circulates bound to C4b binding protein (C4b-BP), while the remainder circulates as "free" protein S. Only free protein S has anticoagulant activity.
Congenital protein S deficiency is an autosomal codominant disorder that is present in 1% to 3% of patients with venous thromboembolism. Heterozygous protein S deficiency carriers have approximately a 10-fold increased risk of venous thromboembolism. Other phenotypic expressions of heterozygous congenital protein S deficiency include recurrent miscarriage, complications of pregnancy (preeclampsia, abruptio placentae, intrauterine growth restriction, and stillbirth) and possibly arterial thrombosis. Three types of heterozygous congenital protein S deficiency have been described according to the levels of total protein S antigen, free protein S antigen, and protein S (APC cofactor) activity in plasma.
| Types of Heterozygous Protein S Deficiency | |||
| Type | Protein S Antigen, Free | Protein S Antigen, Total | Protein Activity |
| I | Decreased | Decreased | Decreased |
| II | Normal | Normal | Decreased |
| III | Decreased | Normal | Decreased |
Type I and III protein S deficiency are much more common than Type II (dysfunctional) protein S deficiency. Type III protein S deficiency appears to be partly due to mutations within the protein S binding region for C4b-BP.
Homozygous protein S deficiency is rare, but can present as neonatal purpura fulminans, reflecting severe intravascular coagulation and fibrinolysis/disseminated intravascular coagulation (ICF/DIC) caused by the absence or near absence of plasma protein S.
Acquired deficiency of protein S is much more common than hereditary protein S deficiency and is generally of unknown hemostatic significance (ie, uncertain thrombosis risk). Among the many causes of acquired protein S deficiency are:
-Vitamin K deficiency
-Oral anticoagulant therapy
-Acute illness (eg, acute thrombosis, recent surgery, or other disorder associated with acute inflammation)
-Liver disease
-ICF/DIC
-Thrombotic thrombocytopenic purpura
-Pregnancy, oral contraceptive, or estrogen therapy
-Nephrotic syndrome
-Sickle cell anemia
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.
Males: 65-160%
Females
<50 years: 50-160%
> or =50 years: 65-160%
Newborn infants have normal or near-normal free protein S antigen (> or =50%), although total protein S antigen is usually below the adult reference range. There are insufficient data concerning protein S activity in normal neonates, infants, and children; but normal or near-normal activity (> or =50%) probably is present by age 3 to 6 months.
Interpretation Provides information to assist in interpretation of the test results
In Type I and Type III congenital deficiency, free protein S antigen is decreased and protein S functional activity is similarly decreased. In Type II congenital (dysfunctional) protein S deficiency, total and free protein S antigen levels are normal but functional activity is decreased.
Patients with acquired free protein S deficiency associated with inflammation-related increase of C4b-BP typically have decreased free protein S antigen (and protein S activity) and normal (or elevated) total protein S antigen. Acquired protein S deficiency is of uncertain clinical hemostatic significance and is associated with a variety of conditions.
Elevated protein S levels are of uncertain clinical significance.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Very high factor VIII (>250%) activity may cause a spuriously low protein S activity result.
Heparin level >1 U/mL may cause a false-high result.
Activated protein C resistance (eg, heterozygosity or homozygosity for the factor V Leiden mutation) may cause a spuriously low protein S activity result.
The presence of a lupus anticoagulant or a specific factor V inhibitor may cause the protein S activity to appear spuriously normal (or elevated), when protein S activity is truly decreased (or normal).
Coumadin therapy may result in decreased protein S activity (and free protein S antigen).
Acute or chronic inflammation can result in decreased protein S activity (and free protein S antigen).
Interpret protein S activity results with caution when any of the above patient conditions are present.
Protein S antigen assay (free protein S antigen, with concomitant or reflexive total protein S antigen assay), rather than protein S activity (functional) assay, is recommended as the initial testing approach for detecting congenital protein S deficiency, because of the greater variety of patient conditions that can interfere with the accuracy of functional testing as compared to antigen testing.
In general, it is preferable not to test for protein S deficiency during acute illness, pregnancy, or postpartum.
The preferred initial test for protein S is the antigen assay S_FX/83049 Protein S Antigen, Plasma, because other patient conditions can interfere with activity-based assays.
Elective testing for protein S deficiency should be delayed for at least 30 days after cessation of warfarin therapy.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Borgel D, Gandrille S, Aiach M: Protein S deficiency. Thromb Haemost 1997 July;78(1):351-356
2. Faioni EM: "Protein S activity" In Laboratory Techniques in Thrombosis-A Manual. Second edition. Kluwer Academic Publishers, Boston, MA, 1999, pp 153-161
3. De Stefano V, Finazzi G, Mannucci PM: Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 1996 May 1;87(9):3531-3544
4. Zoller B, Garcia de Frutos P, Dahlback B: Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995 June 15;85(12):3524-3531
5. Grandrille S, Borgel D, Ireland H, et al: Protein S deficiency: a database of mutations. Thromb Haemost 1997 June;77(6):1201-1214
6. Goodwin AJ, Rosendaal FR, Kottke-Marchant K, Bovill EG: A review of the technical, diagnostic, and epidemiologic considerations for protein S assays. Arch Pathol Lab Med 2002 November;126(11):1349-1366
Method Description Describes how the test is performed and provides a method-specific reference
Plasma protein S activity is measured using a clot-based modified activated partial thromboplastin time assay that reflects the patient's protein S cofactor enhancement of the anticoagulant activity of exogenously added APC that proteolytically inactivates factor V (factor Va, also exogenously added to the test system).(Wolf M, Boyer-Neumann C, Martinoli JL, et al: A new functional assay for human protein S activity using activated factor V as substrate. Thromb Haemost 1989 December 29;62[4]:1144-1145)
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; 12 p.m.
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.
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.
85306
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 |
|---|---|---|
| S_FX | Protein S Activity, P | 31102-7 |
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