Protein C activity

Protein C (PC) activity, which in fact is activated protein C (APC) activity, is determined in a chromogenic assay. PC in test plasma is activated by a fraction of the venom of the Southern Copperhead snake (Agkistrodon contortrix contortrix) to generate APC. The APC then cleaves a chromogenic substrate to generate a coloured product, the intensity of which is directly proportional to the PC activity.
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 C (PC) is the vitamin K dependent zymogen of the serine protease activated protein C (APC), which functions as a regulator of secondary haemostasis by inactivating FVa & FVIIIa within a forming clot. 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 & its non-enzymatic cofactor protein S (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.

Deficiency of PC can be qualitative or quantitative and reduces the effectiveness of haemostasis regulation, thus tipping the balance towards an increased risk of venous thromboembolism.
Reference range: 

77.1 - 126.4

Sample type and Volume required: 
External requests: Citrated platelet poor plasma
420µL x 1 aliquot
Internal requests: please refer to EPR label
Turnaround time: 
7 - 12 days
Special sample instructions: 

The sample should be analysed or manipulated & stored in the laboratory within 4 hours of venepuncture. Please ensure sample tubes are filled exactly to the fill-line as underfilling creates a dilution error and leads to inaccurate results.

Diagnostic Haemostasis and Thrombosis Department
020 7188 2797
St Thomas' Hospital
North Wing - 4th and 5th Floors
Westminster Bridge Road
London SE1 7EH

Laboratory opening times
For clinical advice or interpretation of results, please contact the laboratory in the first instance.

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Last updated: 09/03/2017