Test Catalog

Test Id : PST

Protein S Antigen, Total, Plasma

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

Investigation of patients with a history of thrombosis

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

Method Name
A short description of the method used to perform the test

Only orderable as part of a profile. For more information see PSTF / Protein S Antigen, Plasma.


Latex Immunoassay (LIA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.


Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Protein S Ag, Total, P

Specimen Type
Describes the specimen type validated for testing

Plasma Na Cit

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Only orderable as part of a profile. For more information see PSTF / Protein S Antigen, Plasma.


Patient Preparation: Patient must not be receiving heparin or Coumadin. If the patient is being treated with Coumadin, this should be noted. Coumadin will lower protein S.

Specimen Type: Platelet-poor plasma

Collection Container/Tube: Light-blue top (3.2% sodium citrate)

Submission Container/Tube: Plastic vials

Specimen Volume: 1 mL in 2 plastic vials each containing 0.5 mL

Collection Instructions:

1. For complete instructions, see Coagulation Guidelines for Specimen Handling and Processing.

2. Configure, remove plasma, and spin plasma again.

3. Freeze plasma immediately (no longer than 4 hours after collection) at -20 degrees C or, ideally, < or =-40 degrees C.

4. 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. Each coagulation assay requested should have its own vial.

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Plasma Na Cit Frozen 14 days

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

Investigation of patients with a history of thrombosis

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 hemostatic 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.

Only orderable as part of a profile. For more information see PSTF / Protein S Antigen, Plasma.


Males: 80-160%


<50 years: 70-160%

> or =50 years: 80-160%

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 90-180 days postnatal.*

*See Pediatric Hemostasis References section in Coagulation Guidelines for Specimen Handling and Processing

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.


Table. Types of Heterozygous Protein S Deficiency


Protein S antigen free

Protein S antigen total

Protein S activity














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 / 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, the 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; see PRSNG / Protein S Deficiency, PROS1 Gene, Next-Generation Sequencing, Varies.

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

Total protein S 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 (RF) >300 IU/mL; may lead to an overestimation of the result

-Anti-rabbit antibodies; certain subjects may have aberrant results

-Lipemia: may lead to an overestimation of level

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

1. Laroche P, Plassart V, Amiral J: Rapid quantitative latex immunoassays for diagnosis of thrombotic disorders. Thromb Haemost. 1989:62:379

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. For the Plasma Coagulation Inhibitors Subcommittee for the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1997 June;77(6):1201-1214

5. Marlar RA, Gausman JN, Tsuda H, Rollins-Raval MA, Brinkman HJM: Recommendations for clinical laboratory testing for S deficiency: Communication from the SCC committee plasma coagulation inhibitors of the ISTH. JThromb Haemost 2021;19:68-74

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

Method Description
Describes how the test is performed and provides a method-specific reference

This assay is performed using the Diagnostica Stago LIATEST-Protein S kit on the Instrumentation Laboratory ACL TOP using automated latex immunoassay methodology. The kit methodology is comprised of a reagent with microlatex particles coated with specific antihuman-protein S antibodies. Patient plasma containing 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. The increase in absorption is proportional to the concentration of total protein S antigen present in the patient plasma.(Package insert: Liatest Protein S, Diagnostica Stago, Parsippany, NJ, December 2010)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information


Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

1 to 3 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

7 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test


Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

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  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.


LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
PST Protein S Ag, Total, P 27823-4
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.
PST Protein S Ag, Total, P 27823-4

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports