血液转化医学 血栓与止血研究进展.pptVIP

Abciximab (阿昔单抗)and AMI: EPIC Abciximab Placebo % patients 30 days P=0.06 -83% 26.1 4.5 4.5 4.5 6 months 47.8 % patients - 91% p=0.002 EP: Death +MI+urgent revascularization The EPIC Investigators – am J Cardiol 1996;77:1045-51 “十一五” 863计划生物和医药技术领域重大项目 疫苗与抗体工程 抗体—临床研究项目(11项) 1. 肿瘤抗体药物 2. 心血管疾病抗体药物 抗血小板糖蛋白IIb/IIIa抗体 (SZ-21) (2006AA02A247) 3. 自身免疫病抗体药物 抗自身免疫病拮抗剂 普莱单抗(PLAT,SZ-21)动物实验： 狒狒Folts 模型 动脉脉粥样硬化血栓形示意图 Folts 模型 * * * * # # * Compared with N.S. group P0.01, # Compared with 0.2mg/Kg Pulaimab group P0.01 Pulaimab (SZ21) inhibits thrombosis in dogs Challenge and chance of anti-thrombus Unpublished data Major adverse effects of anti-platelet drugs Major drugs for arterial thrombosis - Anti-platelet Agents: Less potent: ADP antagonists such as Plavix and Effient (bleeding, resistance) Cyclooxygenase inhibitors: aspirin (bleeding, resistance) More potent: Integrin antagonists: Integrilin, Abciximab, Aggrastat Limited short-term in hospital use only due to prolonged bleeding Failed trial for stroke due to brain hemorrhages Major common adverse effect: Bleeding - Anti-coagulants: warfarin, heparin, FXa antagonists etc Challenges and opportunities of anti-thrombosis A2 bloedplaatje A1 GPIb collagen blood vessel A2 A3 New Strategies to prevent arterial thrombosis The platelet GPIb-vWF-subendothelial axis Zhao YM, Ruan C et al. Biochem Pharm, 2012;85:945-53. Challenge and chance of anti-thrombus SZ123 inhibition of arterial thrombosis without affecting bleeding time in dog -- 具有抗动脉血栓作用 -- 血小板数量不下降，出血时间不延长 抗GPIb 单抗 (6B4 、SZ-2) 抗VWF A3 区单抗 ( SZ-123 and SZ-125 ) Targeting collagen-vWF-GPIb and GPIIb/IIIa functions with SZ-series mAbs platelet A1 A3 VWF SZ-2 Pulaimab (SZ-21) platelet Fg Challenge and chance of anti-thrombus SZ-123 SZ-125 - * - 2014-2015年世界血栓日：着重关注静脉血栓栓塞症（VTE） 大多数人对于心脏病或脑卒中有一定的认识，但极少人了解静脉血栓栓塞症（VTE） 世界血栓日最初会着重关注VTE，以提高人们对VTE的认识 心脏病 脑卒中 √ √ 静脉血栓 栓塞症(VTE) ? 静脉血栓栓塞症 由于抗凝蛋白、凝血因子