The endothelial cell protein C receptor: its role in thrombosis.

TL;DR: In this paper, the authors evaluate the concepts that have allowed us to reach the integrated vision on coagulation that we have today, including a pivotal role for the proteases of the co-agulation pathway as well as the regulatory proteins thereof.

TL;DR: The resuscitation-associated coagulopathy (RAC) is secondary to a combination of acidosis, hypothermia and dilution from intravenous blood and fluid therapy, which may further aggravate acidosis and hypoxia resulting in a vicious cycle.

TL;DR: A new image of EPCR is offered in the light of its extended panel of ligands, including Factor VII/VIIa and factor Xa, two other serine proteases that play a central role in haemostasis and are also involved in signalling processes influencing wound healing, tissue remodelling, inflammation or metastasis.

Abstract: Objective—The purpose of this study was to determine the effect of a variant in EPCR (Ser219Gly), previously shown to affect EPCR shedding, on plasma FVII, FVIIa, and downstream markers of activated coagulation. Methods and Results—Statistical analysis was undertaken in ≈2000 healthy middle aged men (NPHSII). Higher soluble EPCR levels were confirmed for Gly allele carriers (P<0.0001). Significantly higher levels of FVII, FVIIa, and downstream markers of activated coagulation in the extrinsic pathway (FIX activation pep [FIXpep]; FX activation pep [FXpep]), and prothrombin F1+2 (F1+2) were identified in baseline samples, in Gly carriers compared to Ser/Ser (P<=0.04 for trend). In repeat samples collected for up to 5 years, levels of FVII and F1+2 were higher in Gly allele carriers compared to Ser/Ser by (FVII: 6.9% CI 5.5 to 8.4 in Ser/Gly; and 23.4% CI 16.3 to 30.8 in Gly/Gly, P<0.0001), (F1+2: 8.1% CI 5.2 to 11.1 in Ser/Gly; 25.2% CI 11.8 to 40.3 in Gly/Gly, P<0.04), confirming reproducibility of findings at baseline. Molar ratios for FIXpep, FXpep, and F1+2 to FVIIa were constant in Ser/Ser and Ser/Gly but tended to be higher in Gly/Gly, reaching statistical significance for FIXpep:FVIIa (P=0.04). Conclusions—These data suggest that higher levels of FVII and FVIIa circulate when EPCR shedding is greatest. Furthermore, these results suggest consequences for activation of extrinsic coagulation.

TL;DR: Roles for PARs in blood vessel formation and other processes during embryonic development are emerging, and whether these reflect new roles for the coagulation cascade and/or PAR signaling to other proteases remains to be explored.

TL;DR: The data presented here suggest that deficiencics in protein S, thrombomodulin, or the platelet receptor for activated protein C might also result in a thromBotic tendency.

TL;DR: Animal studies and preliminary clinical results suggest that protein C/activated protein C supplementation may be useful in reversing microvascular dysfunction, and the mechanisms by which inflammation impairs the function of this pathway are reviewed.

TL;DR: A rapid one-stage clotting assay for protein S to quantitate the level of protein S in their plasma is developed and suggests that protein S deficiency may result in recurrent thrombotic disease.