Protein S Activity

Description: 
The Hemoclot Protein S Kit is a clotting method for the in vitro quantitative determination of Protein S (PS) activity on citrated human plasma.

This test is not currently included in the laboratory's UKAS scope of accreditation to ISO15189:2012.
Clinical details: 
The complex orchestration of cellular and molecular participants of haemostasis achieves a crucial yet fine balance of procoagulant and anticoagulant mechanisms. Deficiencies of natural anticoagulant regulators of secondary haemostasis, such as antithrombin, protein C and protein S, and gain of function mutations in genes for FII and FV, are heritable disorders that can shift this balance and increase the risk of venous thromboembolic disease.Protein S (PS) is the vitamin K dependent, non-enzymatic cofactor for the serine protease activated protein C (APC) which functions as a regulator of secondary haemostasis by inactivating FVa & FVIIIa within a forming clot. Zymogen protein C (PC) attaches to vessel endothelium via a specific receptor, endothelial PC receptor (EPCR) and then migrates across the endothelial surface 'in search' of its activator. If a clot is being formed, some of the thrombin leaks onto the endothelial surface and encounters membrane-bound thrombomodulin (TM), whereupon they form a complex that induces a conformational change in thrombin such that it loses procoagulant activity and instead adopts an anticoagulant role by activating PC. The APC/EPCR complex then dissociates from the TM-throbmin complex and the APC is released to migrate onto the surface of an activated platelet. PC & PS are vitamin K dependent and so bind to surface phospholipid and PS orientates the active site of PC above the platelet surface to facilitate inactivation of substrates by cleavage of a small number of peptide bonds. Inactivation of FVIIIa additionally requires zymogen FV to operate synergistically with PS in a cofactor role.Approximately 60% of PS circulates bound to C4b-binding protein and is largely unavailable for functioning as a cofactor for APC. The remainder is termed free protein S (FPS) and is directly available for APC cofactor function. PS also operates as a cofactor for tissue factor pathway inhibitor. Deficiency of PS reduces the effectiveness of haemostasis regulation and tips the balance towards an increased risk of venous thromboembolism. Protein S deficiency, either congenital or acquired, may lead to serious thrombotic events such as thrombophlebitis, deep vein thrombosis or pulmonary embolism. Two-thirds of patients with a congenital deficiency of free protein S (levels < 50% of normal) may present with venous thrombosis in young adulthood. In patients with a history of thrombosis, the prevalence may be as high as 2-6%. Acquired protein S deficiency may be seen during pregnancy, oral contraceptive and oral anticoagulant therapy, liver disease, antiphospholipid syndrome, diabetes mellitus, postoperative complications, septicaemia and various inflammatory syndromes. A decreased protein S activity may be the result of low concentrations or abnormal function of the protein S molecule. The laboratory diagnosis of protein S deficiency may require both quantitative and functional determination. The measurement of plasma levels, of both free and total protein S, and the protein S activity is useful in determining the type of defect in patients with protein S deficiency. Protein S deficiency can be sub-classified on the basis of Total protein S (TPS), FPS and PS activity assays:- Type I - parallel reduction in FPS and TPS. Type II - normal FPS and TPS with decreased activity, indicative of a circulating variant. Type III - clear reduction of FPS with TPS in the reference range.
Reference range: 

Male =56-118%  

Female =54-100%

Synonyms or keywords: 
protein S activity, PS Act.
Units: 
%
Sample type and Volume required: 
External requests: Citrated platelet poor plasma (500µL x 1 aliquot).
Internal requests: please refer to EPIC label.
Call in advance: 
Yes
Turnaround time: 
7-10 days
Special sample instructions: 

The sample should be analysed or processed & stored within 8 hours of venepuncture. Please ensure sample tubes are filled exactly to the fill-line as underfilling or overfilling creates a dilution error and leads to inaccurate results.

Storage and transport: 
It is advised that citrated plasma is frozen prior to transport and sent to the laboratory on dry ice to maintain sample quality and integrity. If whole blood citrate sample is sent, it is required to be sent at room temperature and must arrive to the laboratory within 8 hours of venepuncture.
Contacts:
Diagnostic Haemostasis and Thrombosis Department
St Thomas': 020 7188 2797; Guy's: 020 7188 7188 ext. 53860
St Thomas' Hospital
North Wing - 4th and 5th Floors
Westminster Bridge Road
London SE1 7EH

Laboratory opening times
24/7

Guy's Hospital
Southwark Wing - 4th Floor
Great Maze Pond
London SE1 9RT

Outside core hours, contact Duty Haemostasis Biomedical Scientist
For clinical advice or interpretation of results, please contact the laboratory in the first instance.

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Last updated: 04/10/2023