HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Plasma levels of endothelial protein C receptor respond to anticoagulant treatment

The endothelial protein C receptor (EPCR) facilitates protein C activation and plays a protective role in the response to Esche-richia coli–mediated sepsis in primates. Previously, a soluble form of EPCR (sEPCR) in human plasma was character-ized, and several studies indicated that generation of sEPCR is regulated by in-flammatory mediators, including throm-bin-mediated up-regulation of surface metalloproteolytic activity in vitro. This study addressed the question of whether plasma sEPCR levels reflect changes in thrombin generation in patients undergo-ing anticoagulant treatment. The sEPCR levels in patients treated with coumarin-type oral anticoagulants were signifi-cantly lower than those in healthy asymp-tomatic adult volunteers (105.3 6 70.8 ng/mL [n 5 55] versus 165.8 6 115.8 ng/mL [n 5 200]; P <.0001). A similar de-cline in plasma sEPCR levels was found in patients treated with unfractionated heparin. In healthy volunteers, sEPCR levels declined to about 100 ng/mL within 3 days after initiation of an 8-day period of warfarin administration and increased within 2 days after its cessation. Plasma sEPCR levels returned to pretreatment values within 1 week, and the changes in plasma sEPCR levels mirrored changes in values for international normalized ra-tios. A similar decline in sEPCR levels with time was observed in 7 patients beginning treatment with warfarin for a thrombotic disorder. Prothrombin frag-ment 1 1 2 levels also decreased in volun-teers and patients given warfarin. These results show that plasma sEPCR levels decline in response to treatment with anticoagulants whose mechanism of ac-tion is known to decrease in vivo throm-bin production. (Blood. 2002;99:526-530) © 2002 by The American Society of Hematolog