Mechanisms of thrombosis delay in Klkb1^−/− mice. In the absence of prekallikrein (PK), there is reduced plasma bradykinin (BK) generation from HK bound to its triple-receptor complex. Expression of the bradykinin B2 receptor (B2R) is also reduced. Similar to our recent observation in Bdkrb2^−/− (B2R KO) mice,¹⁸  the Mas receptor in the renin-angiotensin system is overexpressed to compensate for reduced BK B2R expression in Klkb1^−/− mice. In Klkb1^−/− mice, normal levels of Ang-(1-7) interacting with an overexpressed Mas receptor results in increased plasma prostacyclin (PGI₂). The elevation of PGI₂ is sufficient to increase 2 vasculoprotective transcription factors, Sirt1 and KLF4. Elevation of Sirt1 and/or KLF4 reduces the risk of thrombosis by inhibiting TF expression. In Klkb1^−/− mice, the Mas/prostacyclin axis counterbalances the reduction in BK and B2R to reduce thrombosis risk independent of less contact activation.