This website is intended for Healthcare Professionals outside of the UK and US.

Proteinc Cover Desktop

Protein C and Coagulation

What is the role of Protein C in blood Coagulation?

Effective blood coagulation depends on the correct balance and interaction of different pro- and anti-coagulation factors, as well as vessel wall elements and cellular components of the blood.1

Protein C (PC), a naturally occurring vitamin K-dependent anti-coagulant, is an important component of this system.1.2 Its primary role is to regulate the activity of the coagulant thrombin, a key enzyme in the coagulation cascade, which, once activated, leads to fibrin formation and blood clotting.1.2

PC is synthesised in the liver as an inactive enzyme precursor known as a zymogen, which is converted to its active form by forming a complex with the thrombin-thrombomodulin complex on the surface of endothelial cells, facilitated by binding to the endothelial PC receptor (EPCR).1 Activated PC (APC) inactivates the procoagulation factors Va (FVa) and VIIIa (FVIIIa) that promote the generation of thrombin from its precursor molecule prothrombin.1

Thus, PC activation ultimately leads to thrombin inactivation, thereby inhibiting blood clotting. This inactivation occurs at the location of thrombin formation.1,3

In terms of deactivation of PC, the half-life of APC in plasma is about 20 minutes. Once formed, it is immediately degraded by the protein C inhibitor (PCI) and α1-antitrypsin and, to a lesser extent, α2-macroglobulin and α2-antiplasmin.1

PC also has an indirect pro-fibrinolytic (i.e., clot breakdown) function as it binds to plasminogen activation inhibitor-1 (PAI-1), thereby increasing the activity of tissue type plasminogen activator (tPA).4

In addition, due to reduced thrombin generation, the activation of thrombin activatable fibrinolysis inhibitor (TAFI; an inhibitor of plasmin) is diminished as a result of PC activity, thus resulting in increased clot breakdown.1,4 PC also has anti-inflammatory and cytoprotective functions.1,4


Overview of the activation and role of protein C

6.scpcd Desktop Protcand Coagulation Maquette 1250Px

EPCR=endothelial protein C receptor; FVa=factor Va; FVIIIa=factor VIIIa; PAI=plasminogen activator inhibitor; TAFI=thrombin-activatable fibrinolysis inhibitor Adapted from Knoebl 20081

Protein C is activated on the endothelial cell surface by thrombin, bound to thrombomodulin and endothelial cell protein C receptor (EPCR). Together with its cofactor protein S, activated protein C inhibits factors VIIIa and Va. Furthermore, protein C has profibrinolytic, anti-inflammatory and antiapoptotic properties.


  1. Mosnier LO, et al. Protein C, Protein S, Thrombomodulin, and the Endothelial Protein C Receptor Pathways. In: Marder, VJ, et al. (eds.) Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 6th ed. Philadelphia, PA, USA: Wolters Kluwer Health; 2012.

  2. Goldenberg N, Manco-Johnson M. Protein C deficiency. Haemophilia. 2008;14(6):1214–1221.

  3. Gale KD. Continuing Education Course #2: Current Understanding of Hemostasis. Toxicol Pathol. 2011;39(1):273-280.

  4. Knoebl PN. Human protein C concentrates for replacement therapy in congenital and acquired protein C deficiency. Drugs of Today. 2008;44(6):429-441.


Interested in severe congenital protein c
Deficiency (SCPCD) and its management ?
Sign up below !

Sorry! There are some errors below that need to be fixed.
There seems to have been an error when sending the form.

You have the right to opt out of receiving such electronic communications and/or our newsletter, at any time, by using the opt out link in the communication or by contacting us at For more information on how Takeda processes your personal data, please refer to our Privacy Notice

Please include @ in your email adress


Thank you for submitting your details

You are about to leave this website. Takeda has no influence or control over the content of this third party website.
Continue Cancel
This website is intended for Healthcare Professionals outside of the US and the UK. The website has been developed by Takeda in accordance with industry and legal standards. Takeda makes every reasonable effort to include accurate and current information. However, the information provided on the website is not exhaustive.
Please tick the boxes to enter the site

Yes, I am a healthcare professional outside of the US and UK


No, I am not a healthcare professional outside of the US and UK