Blocking EPCR–protein C binding markedly diminishes the circulating APC that is generated in response to thrombin infusion.

(A) Animals were infused with thrombin (2 U/kg per minute for 60 minutes) alone and the circulating APC levels were determined at the times indicated as described under “Materials and methods” (■). Two to 3 days later the same animals were infused with 5 mg/kg anti-EPCR mAb 1494 30 minutes before repeating the thrombin infusion described above (○). The circulating APC concentrations were then determined at the times indicated. (B) Plasma samples were collected from the animals infused with thrombin alone or thrombin plus the anti-EPCR antibody at the same time the samples were taken for APC level determination. The aPTT assays were then performed on these samples.