Test ID: PSTF
Protein S Antigen, 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
Investigation of patients with a history of thrombosis
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PSF | Protein S Ag, Free, P | No | Yes |
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PST | Protein S Ag, Total, P | No | No |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
If this test is abnormal, then total plasma protein S antigen will be performed at an additional charge.
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
PSF/80338: Automated Latex Immunoassay (LIA)
PST/80994: Latex Immunoassay (LIA)
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 Antigen, Total and Free
Protein S, Free and Total Antigen
S Protein Antigen
Total Protein S Antigen
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 vials
Specimen Volume: 1 mL in 2 plastic vials each containing 0.5 mL
Collection Instructions:
1. Spin down, remove plasma, and spin plasma again.
2. Freeze specimens immediately at < or =-40 degrees C, if possible.
3. Send specimens in the same shipping container.
Additional Information:
1. Double-centrifuged specimen is critical for accurate results as platelet contamination may cause spurious results.
2. If the patient is being treated with Coumadin, this should be noted. Coumadin will lower protein S.
3. Each coagulation assay requested should have its own vial.
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 glycoprotein present in platelets and synthesized within the liver and endothelial cells. Protein S works as part of the natural anticoagulant system by acting as a cofactor to activated protein C (APC) in the proteolytic inactivation of procoagulant factors Va and VIIIa. In addition, protein S has direct APC-independent anticoagulant activity by inhibiting formation of the prothrombin and tenase complexes, possibly due to its high affinity for anionic phospholipid membranes. In human plasma, protein S forms a complex with the compliment regulatory protein, C4b-binding protein (C4bBP). Of the total plasma protein S, approximately 60% circulates bound to C4bBP while the remaining 40% circulates as "free" protein S. Only free protein S has anticoagulant function. C4bBP is composed of 6 or 7 alpha-chains and 1 or no beta-chain (C4bBP-beta). Different C4bBP isoforms are present in plasma, but only C4bBP-beta binds protein S.
Congenital protein S deficiency is an autosomal dominant disorder that is present in 2% to 6% of patients with venous thrombosis. Patients with protein S deficiency have an approximately 10-fold increased risk of venous thrombosis. In addition they may also experience recurrent miscarriage, complications of pregnancy (preeclampsia, abruptio placentae, intrauterine growth restriction, and stillbirth) and possibly arterial thrombosis.
Three types of protein S deficiency have been described according to the levels of total protein S antigen, free protein S antigen, and protein S activity in plasma. Types 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 C4bBP-beta.
Homozygous protein S deficiency is rare, but can present as neonatal purpura fulminans, reflecting severe disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF) caused by the absence of plasma protein S.
Acquired deficiency of protein S has causes that are generally of unknown haemostatic significance (ie, uncertain thrombosis risk), and is much more common than hereditary protein S deficiency. Acquired protein S deficiency can present through vitamin K deficiency, oral anticoagulant therapy, liver disease, DIC/ICF, thrombotic thrombocytopenia purpura, pregnancy or estrogen therapy, nephritic syndrome, and sickle cell anemia. As an acute-phase reactant, plasma C4bBP levels increase with acute illness and may cause acquired free protein S deficiency.
Measurement of plasma free protein S antigen is performed as the initial testing for protein S deficiency. When the free protein S antigen level is below the age- and sex-adjusted normal range, reflexive testing will be performed for total plasma protein S antigen.
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.
TOTAL
Males: 80-160%
Females
<50 years: 70-160%
> or =50 years: 80-160%
FREE
Males: 65-160%
Females
<50 years: 50-160%
> or =50 years: 65-160%
Normal, full-term newborn infants or healthy premature infants may have decreased levels of total protein S (15-50%); but because of low levels of C4bBP, free protein S may be normal or near the normal adult level (> or =50%). Total protein S reaches adult levels by 90 to 180 days postnatal.*
*See Pediatric Hemostasis References in Coagulation Studies in Special Instructions.
Interpretation Provides information to assist in interpretation of the test results
Protein S values vary widely in the normal population and are age- and sex-dependent.
| Types of Heterozygous Protein S Deficiency | |||
|
| Protein S Antigen Free | Protein S Antigen Total | Protein S Activity |
| I | Low | Low | Low |
| II | Normal | Normal | Low |
| III | Low | Normal | Low |
Protein S and C4bBP are coordinately regulated, and an increased total protein S antigen and low free protein S antigen most commonly reflect acute or chronic inflammation or illness with an associated increase in plasma C4bBP.
For patients in whom hereditary protein S deficiency is strongly suspected and the free plasma protein S antigen level is normal, consideration should be given to testing of free protein S activity, S_FX/80775 Protein S Activity, Plasma, for detecting type II protein S deficiency (which is rare).
An increased total protein S antigen is of uncertain clinical significance because free protein S antigen levels are usually normal, in such situations. However, the total protein S antigen level may be helpful in distinguishing acquired versus congenital protein S deficiency. High normal or increased total protein S antigen and reduced free protein S antigen suggests acquired protein S deficiency, as may be seen in pregnancy or inflammation. In contrast, low normal or decreased total protein S antigen and reduced free protein S antigen suggests vitamin K deficiency or a warfarin effect, but also could reflect congenital protein S deficiency (type I or III).
Vitamin K deficiency, oral anticoagulant therapy, presence of liver disease, or disseminated intravascular coagulation/intravascular coagulation and fibrinolysis (DIC/ICF) are common acquired causes of protein S deficiency, which is of uncertain significance when such conditions are present. Concomitant assay of coagulation factor II activity may be helpful in differentiating congenital protein S deficiency from oral anticoagulation effects, but supportive data are currently suboptimal.
Differentiation of congenital and acquired protein S deficiency requires clinical correlation and may require repeated laboratory study of the patient and selected family members in some instances. DNA-based testing may be helpful, but is generally not yet available.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Total
Protein S total antigen results are potentially affected by:
-Heparin (unfractionated or low-molecular-weight) >4 U/mL
-Hemoglobin >2 g/L
-Bilirubin >100 mg/L
-Rheumatoid factor >300 IU/mL; may lead to an overestimation of the result
-Antirabbit antibodies; certain subjects may have aberrant results
-Lipemic specimen may lead to an overestimation of level
Free
Free protein S antigen results are potentially affected by:
-Heparin (unfractionated or low-molecular-weight) >4 U/mL
-Hemoglobin >200 mg/dL
-Bilirubin >25 mg/dL
-Triglycerides >1,500 mg/dL
-Platelets >10(10)/L
-Rheumatoid factor >900 IU/mL
-Factor V Leiden mutation (APC-R)
Supportive Data
A retrospective review of Mayo Special Coagulation Laboratory data found that of 584 patients tested sequentially, only 4 patients demonstrated a pattern of normal free protein S antigen with decreased total protein S antigen. Three of these patients were receiving oral anticoagulant therapy and 1 had liver disease. There were 8 patients with probable congenital protein S deficiency. Of this group, all had significantly reduced levels of free protein S antigen and normal or mildly reduced levels of total protein S antigen. We conclude that omission of routine measurement of total protein S antigen and substituting measurement of free protein S antigen with reflexive testing of total protein S antigen only for decreased free protein S antigen would not decrease clinical sensitivity of this assay system for detecting hereditary protein S deficiency.
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. De Stefano V, Finazzi G, Mannucci PM: Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 1996 May 1;87(9):3531-3544
3. 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
4. Grandrille S, Borgel D, Ireland H, et al: Protein S deficiency: a database of mutations. Thromb Haemost 1997 June;77(6):1201-1214
5. Wolf M, Boyer-Neumann C, Peynaud-Debayle E, et al: Clinical applications of a direct assay of free protein S antigen using monoclonal antibodies. A study of 59 cases. Blood Coagul Fibrinolysis 1994 April;5(2):187-192
6. Laroche P, Plassart V, Amiral J: Rapid quantitative latex immunoassays for diagnosis of thrombotic disorders. Thromb Haemost 1989:62:379
7. 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;126:1349-1366
8. Sales M, Begona A, Rosen S: IL Test Free Protein S: A diagnostic tool for protein S deficiency. IL Laboratories; Hemostaisis Monograph
9. Serra J, Sales M, Chitolie A, et al: Multicentre evaluation of IL Test Free PS: a fully automated assay to quantify free protein S. Thromb Haemost 2002;88:975-983
Method Description Describes how the test is performed and provides a method-specific reference
Total
This assay is performed using the Diagnostica Stago LIATEST Protein S Kit on the Beckman Coulter ACL TOP. Protein S total antigen is determined using automated latex immunoassay methodology. This methodology is comprised of a reagent with microlatex particles coated with specific antihuman total protein S antibodies. Patient plasma containing total protein S antigen is combined with the latex reagent causing the antibody-coated latex particles to agglutinate and form aggregates. The aggregates form diameters greater than the wavelength of the light (405 nm) passing through causing absorption of the light. This change in absorption is measured over time and reported as delta optical density (OD). The increase in absorption is proportional to the concentration of protein S total antigen present in the patient plasma.
Free
This assay is performed using the HemosIL Free Protein S kit on the Beckman Coulter ACL TOP. The assay uses latex immunoassay methodology to determine the presence of free protein S. It consists of 2 latex reagents, one being latex particles coated with purified human C4BP and the other is latex particles coated with a monoclonal antibody directed against human protein S. Patient plasma is combined with the purified C4BP which reacts with a high affinity for free protein S in the patient plasma. The free protein S adsorbed on the C4BP latex triggers the agglutination reaction with the second latex reagent. The aggregates form diameters greater than the wavelength of the light (405 nm) passing through causing absorption of the light. This change in absorption is measured over time and reported as delta OD. The increase in absorption is proportional to the concentration of free protein S antigen present in the patient plasma.
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.
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-Free
85305-Total (if appropriate)
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 |
|---|---|---|
| PSF | Protein S Ag, Free, P | 27821-8 |
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