Role of fibrinogen vs fibrin in antimicrobial host defense and hemostasis/thrombosis. (A) Fibrinogen is involved in hemostasis/thrombosis because it is necessary for platelet aggregation. Similarly, fibrinogen binds specifically to some cells, such as neutrophils and some bacteria, as part of antimicrobial host defense and may have other roles as well. Thrombin cleaves the fibrinopeptides of fibrinogen converting it to fibrin, which aggregates to form a clot. Fibrin clots are a necessary part of hemostasis/thrombosis, but a potential role of fibrin polymer in antimicrobial host defense has not been so clearly demonstrated prior to this paper. (B) In Fib^AEK mice, fibrinopeptide A cannot be cleaved, so no fibrin clot is formed. These mice show impaired hemostasis and thrombosis and compromised antimicrobial host defense. Hemorrhage is more common, and there is delayed or incomplete vessel occlusion. Survival of Fib^AEK mice was less than that of wild-type mice but better than fibrinogen knockout mice, and no females survived pregnancy. These mice show severely limited intraperitoneal clearance of S aureus, but increased peritonitis survival compared with afibrinogenemic mice.