Function of FXI in hemostasis and thrombosis. Hemostasis: At sites of injury, fibrin formation is initiated by the tissue factor (TF)/factor VIIa complex. FXI is activated by thrombin and contributes to sustained fibrin production when TF activity is reduced by reaction with tissue-factor pathway inhibitor (TFPI). Thrombosis: On activated platelet surfaces, released polyphosphates (polyP) initiate contact activation of FXII that, in turn, activates FXI. Further FXI activity is generated by feedback activation. Targeting FXI with ASO abolishes pathologic thrombosis but has minor impact on hemostasis. (Professional illustration by Kenneth X. Probst.)