Sepsis stage–related response to infusion of aPC variants. Gram-positive peritonitis was induced in the indicated numbers of wild-type mice by intraperitoneal infection with ∼10⁸ live S aureus bacteria. Wild-type (wt) mouse aPC, or the recombinant mouse aPC variants 5A-aPC (5A; signaling-selective) and E149A-aPC (E149A; hyperantithrombotic) were administered by IV injection at 150 μg/kg body weight within 30 minutes after infection (0 hours) and at 10 or 18 hours after infection. Significance of differences in cumulative 7-day survival was determined by Mantel-Cox log-rank analysis of Kaplan-Meyer survival plots. PBS, phosphate-buffered saline.