The protein C system in inflammation and cancer: a critical role for thrombomodulin

Published: June 3, 2009
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The protein C system comprises the cellular receptors thrombomodulin (TM) and endothelial protein C receptor (EPCR), and the soluble proteins C and S. Thrombin binds to TM and this complex jointly with protein C bound to EPCR generates activated protein C (APC). One of the main functions of APC in blood coagulation is to regulate the rate of thrombin generation, in complex with protein S, by inhibiting factors Va and VIIIa through limited proteolytic cleavage.1 Defects in one of the factor V cleavage sites for APC, e.g. the factor V Leiden variant, renders this protein partially resistant to cleavage by APC and the clinical result is an increased risk of venous thrombosis. Similarly, heterozygous deficiencies in PC or PS cause a marked increase in the risk of venous thrombosis. Complete absence of these proteins is hardly compatible with life due to massive disseminated intravascular coagulation.

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Spronk, H., & Ten Cate, H. (2009). The protein C system in inflammation and cancer: a critical role for thrombomodulin. Hematology Meeting Reports (formerly Haematologica Reports), 1(9). https://doi.org/10.4081/hmr.v1i9.330