Coagulation is essential under normal physiological conditions and several pathological conditions (e.g. cancer, atherosclerosis and sepsis) have enhanced coagulation. Thrombin, a serine protease, catalyzes the conversion of fibrinogen to fibrin, which forms blood clots in conjunction with platelets. Heparin cofactor II (HCII) is a thrombin inhibitor and the only known serpin to be activated by IdoA-containing CS/DS (Fig. 4D). The HCII binding site to CS/DS differs from that to HS 59. The HCII binding structures in CS/DS contain IdoA-2S-GalNAc-4S 60 or GlcA-GalNAc-4,6-disulfated 61 in hexa- and octasaccharides as minimal binding motifs. The complex CS/DS-HCII is considered to be the major anticoagulant system after injury of the vessel wall 60,62,63. CS/DS containing 2-O-sulfated IdoA also controls coagulation by activating protein C 64.
