凝血瀑布与抗凝药的临床应用 教学课件.ppt

新型抗凝药物的研发倾向于抑制凝血瀑布中的单一凝血因子。如Xa因子和IIa因子。 * 磺达肝癸钠与抗凝血酶Ⅲ结合后，使抗凝血酶Ⅲ抑制因子Ⅹa的能力增加约300倍，并抑制了凝血酶的形成和血栓的增大。 * 利伐沙班，直接抑制Xa因子。 Weitz JI Bates SM. New anticoagulants. J Thromb Haemost 2005;3:1843–1853 * 2008年达比加群--口服直接凝血酶抑制剂问世，直接作用抑制凝血酶。 组织因子途径抑制剂（TFPI）： There are many targets for novel anticoagulants in the coagulation pathway: Tissue factor pathway inhibitor (TFPI) bound to Factor Xa inactivates the tissue factor (TF)–Factor VIIa complex, preventing initiation of coagulation Activated protein C (APC) degrades Factors Va and VIIIa, and thrombomodulin (soluble; sTM) converts thrombin (Factor IIa) from a procoagulant to a potent activator of protein C Fondaparinux and idraparinux indirectly inhibit Factor Xa, requiring antithrombin (AT) as a cofactor Direct (AT-independent) inhibitors of Factor Xa include rivaroxaban (BAY?59-7939), LY517717, YM150 and DU-176b (all orally available), and DX-9065a (intravenous) Oral, direct thrombin inhibitors include ximelagatran (now withdrawn) and dabigatran Weitz JI Bates SM. New anticoagulants. J Thromb Haemost 2005;3:1843–1853 * 达比加群--口服直接凝血酶抑制剂： 结合于凝血酶的纤维蛋白特异结合位点 阻止纤维蛋白原裂解为纤维蛋白 从而阻断了凝血瀑布网络的最后步骤及血栓形成。 可以从纤维蛋白一凝血酶结合体上解离，发挥可逆的抗凝作用。 组织因子途径抑制剂（TFPI）： There are many targets for novel anticoagulants in the coagulation pathway: Tissue factor pathway inhibitor (TFPI) bound to Factor Xa inactivates the tissue factor (TF)–Factor VIIa complex, preventing initiation of coagulation Activated protein C (APC) degrades Factors Va and VIIIa, and thrombomodulin (soluble; sTM) converts thrombin (Factor IIa) from a procoagulant to a potent activator of protein C Fondaparinux and idraparinux indirectly inhibit Factor Xa, requiring antithrombin (AT) as a cofactor Direct (AT-independent) inhibitors of Factor Xa include rivaroxaban (BAY?59-7939), LY517717, YM150 and DU-176b (all orally available), and DX-9065a (intravenous) Oral, direct thrombin inhibitors include ximelagatran (now withdrawn) and dabigatran Weitz JI Bates SM.