The roles of polyP in blood clotting vary depending on polymer length. (A) Microbial long-chain polyP (ranging from less than a hundred phosphates to several thousand phosphate units long) acts at 4 points in the clotting cascade, indicated in red: 1 initiates the contact pathway of blood clotting5,25,27 ; 2, accelerates factor V activation and abrogates TFPI function (the latter not shown explicitly)5,27 ; 3, enhances fibrin polymerization24,27,30 ; and 4, accelerates factor XI back-activation by thrombin.29 (B) Platelet-size polyP (∼ 60 to ∼ 100 phosphate units long) acts most potently at 3 points in the clotting cascade, indicated in red: 2 indicates abrogates TFPI function (and overlaps the minimal size necessary to accelerate factor V activation)5,27 ; 3, overlaps the minimal size necessary to enhance fibrin polymerization24,27,30 ; and 4, accelerates factor XI back-activation by thrombin.29 Reproduced from Choi et al with permission.29