Test Catalog

Test Id : SFX

Protein S Activity, Plasma

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, ie, 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
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

Optical Clot-Based

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 Activity, P

Lists additional common names for a test, as an aid in searching

Functional Protein S

Protein S Activity, Plasma

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

Patient Preparation: Patient must not be receiving Coumadin.

Specimen Type: Platelet-poor plasma

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

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

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 specimen immediately (no longer than 4 hours after collection) at --40 degrees C or below

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

Second-order testing for diagnosis of congenital or acquired protein S deficiency, ie, 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

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.


 Table. Types of heterozygous protein S deficiency


Free protein S antigen

Total protein S antigen

Protein activity














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 variants 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


-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: 65-150%


<50 years: 50-150%

> or =50 years: 65-150%

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.

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-binding protein typically have decreased free protein S antigen and protein S activity with 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.

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

Direct-acting oral anticoagulants (eg, direct thrombin inhibitors, such as dabigatran [Pradaxa], argatroban [Acova], bivalirudin [Angiomax]) and direct factor Xa inhibitors (eg, rivaroxaban [Xarelto], apixaban [Eliquis], edoxaban [Savaysa]) may cause the protein S activity to appear spuriously normal (or elevated), when protein S activity is truly decreased (or normal). Clinical correlation is suggested, and in the absence of anticoagulation therapy, consider repeating the protein S activity and antigen assay.


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. Elective testing for protein S deficiency should be delayed for at least 30 days after cessation of warfarin therapy.

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

1. Borgel D, Gandrille S, Aiach M: Protein S deficiency. Thromb Haemost. 1997 Jul;78(1):351-356

2. Faioni EM: Protein S activity. In: Laboratory Techniques in Thrombosis-A Manual. 2nd ed. Kluwer Academic Publishers; 1999:153-161

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 Jun 15;85(12):3524-3531

5. Grandrille S, Borgel D, Ireland H, et al: Protein S deficiency: a database of mutations. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1997 Jun;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 Nov;126(11):1349-1366

7.  Yohe S, Olson J: Thrombophilia: assays and interpretation. In: Kottke-Marchant Wiley K, ed. Laboratory Hematology Practice. Blackwell Publishing; 2012: 38:492-508

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

The functional activity of free protein S is performed on the instrumentation laboratory ACL TOP. It is determined by measuring the degree of prolongation of a prothrombin time in the presence of the recombinant human tissue factor, phospholipids, calcium ions, and activated protein C. The protein S activity is correlated with the prolongation of the clotting time of protein S deficient plasma to which diluted sample has been added. The clotting time is directly proportional to the amount of functional protein S in the patient's plasma and can be quantified using a standard curve.(Package insert: HemosIL Protein S Activity. Instrumentation Laboratory Company; Rev 08/2012)

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 4 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.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. 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
SFX Protein S Activity, P 27822-6
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.
SFX Protein S Activity, P 27822-6

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

Test Update Resources

Change Type Effective Date
New Test 2023-05-16