Fibrinogen α-chain truncation at Arg₂₇₁ leads to a shortened αC region, a naturally occurring mutation (fibrinogen Otago) leading to hypodysfibrinogenemia (reduced levels and function). This mutation does not dramatically affect hemostasis (bleeding) or fibrinogen-mediated survival to microbial infection, but reduces the development of venous thrombosis, in mice. Similarly, siRNA-induced reduction of circulating fibrinogen levels to ∼10% retain fibrinogen functionality, hemostatic and antimicrobial functions, while still preventing venous thrombosis. mRNA, messenger RNA. Professional illustration by Patrick Lane, ScEYEnce Studios.