Test Overview

Test Methodology

Clot-based endpoint assay.

Test Usage

Second order testing for diagnosis of congenital or acquired protein S deficiency, for example, as an adjunct to initial testing based on results of free protein S antigen assay (PSAGF). Evaluating patients with a history of venous thromboembolism.

Reference Range*

ADULT: Male: 75 - 140%; Female: 55 - 125%. There are insufficient data concerning protein S activity in neonates, infants, and children, but normal or near normal activity (>= 50%) probably is present by age 3 to 6 months.

* Reference ranges may change over time. Please refer to the original patient report when evaluating results.

Test Limitations

Heparin levels up to 1 IU/mL do not affect test results. Higher heparin levels may lead to an over-estimation of the protein S level. It has been noted that the lupus anticoagulants (LA) and/or the anti-phospholipid antibodies (APA), if present in the plasma being tested, may interfere in the assay. Thrombin inhibitors (e.g., hirudin, argatroban) present in the sample to be tested may lead to an over-estimation of the protein S level.

Test Details

Days Test Performed


Analytic Time

4 hours

Soft Order Code


MiChart Code

Protein S Activity



Protein S Activity, P

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Specimen Requirements

Offsite Collection Instructions

Collect specimen in a blue top (citrate 3.2%) tube. Mix by inversion. Specimen should arrive at lab within 3 hours of collection; transport at room temperature. Alternatively, centrifuge, aliquot plasma into a plastic vial, and freeze the specimen within 4 hours of collection. Transport frozen specimen on dry ice. Collection of the blood through lines that have been previously flushed with heparin should be avoided. If the blood must be drawn through a VAD (vascular access device), the line should be flushed with 5 mL of saline and the first 5 mL of blood or six dead space volumes of the VAD discarded.

Special Handing

Note that the Protein S Antigen, Free (PSAGF) assay is the recommended test for screening for inherited Protein S Deficiency.

Rejection Criteria

Specimens will be rejected if not properly filled, clotted, grossly hemolyzed, or contaminated with heparin.


This test is not indicated in patients receiving warfarin (coumadin) therapy.


Blue Top Tube

Normal Volume

Full 2.7mL tube or 1mL plasma aliquot

Minimum Volume

Full 1.8mL tube or 1mL plasma aliquot

Additional Information

Protein S is a vitamin K dependent anticoagulant protein synthesized in the liver (and endothelium). Protein S circulates in plasma alone ("free") or reversibly bound to the complement regulatory protein C4b binding protein (C4bBP). C4bBP is an acute phase reactant and may be increased in inflammatory conditions, causing an acquired decrease of free protein S. Only free protein S has anticoagulant activity.

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