凝血机制- PowerPoint Presentation.pptVIP

止血、凝血机制 正常止血机制 初期止血 血管内皮细胞损伤，内皮下组织成分暴露（主要为胶原），血小板发生黏附、聚集和释放反应，形成血小板血栓 二期止血 凝血、抗凝和纤溶诸系统相互协调、有序完成的过程，血浆中一系列凝血因子经级联酶促反应依次被活化,最终形成纤维蛋白凝块 ◆ 分为1型、2型（2A、2B、2N、2M）、3型； ◆ 多为常染色体显性遗传，3型和2N型为常染色体隐形遗传； ◆ 皮肤紫癜、粘膜出血，特别是牙龈和鼻出血最常见，女性患 者表现为月经增多； ◆ 发病机制： VWF质或量的异常； * Normal hemostasis（止血） VII VII TF-VIIa X Xa II IIa Fbgn Fibrins IX TF Fibrinp VIII V TF TF-VIIa IXa adhesion 粘附 aggregation 聚集 coagulation pathway 凝血途径 初期止血机制 TXA2 ADP 纤维蛋白原 凝血酶 PF4 -TG PDGF 纤维蛋白 PGI2 聚集 白色血栓 释放 粘附 v WF EC SE + + Fibrin Fibrinogen Prothrombin Thrombin FVa FX FXa FVIIIa FIXa TF/FVIIa Generation of thrombin TF/FVIIa Platelets adhere to VWF bound to sub-endothelium collagen The platelet is activated and fibrinogen and other adhesive proteins engage with GpIIb/IIIa Tissue factor initiates thrombin generation. Thrombin activates factors V and VIII Thrombin converts fibrinogen to fibrin Fibrin acts as a cofactor for thrombin-dependent FXIII activation. + + FVIII FV Procoagulant Fibrin Fibrinogen Prothrombin Thrombin FVa FX FXa FVIIIa FIXa Procoagulant roles for thrombin TF/FVIIa FXIII FXIIIa Cross linked fibrin 1 2 3 4 TF/FVIIa Thrombin binds to GpIba, cleaves PAR and GpV (not shown) and further activates platelets Platelet Activated Platelet exposure/ engagement GpIIb + GpIIIa GpIba + GpIb + GpIX + GpV GpIa + GpIIa Procoagulant + + Fibrin Fibrinogen Prothrombin Thrombin FVa FX FXa FVIIIa FIXa TF/FVIIa 5 PARs activated Procoagulant roles for thrombin 6 GpV cleaved TF/FVIIa Thrombin bound to GpIba activates FXI, leading to further thrombin generation + + Procoagulant Fibrin Fibrinogen Prothrombin Thrombin FVa FX FXa FVIIIa FIXa Procoagulant roles for thrombin TF/FVIIa FXIII FXIIIa Cross linked fibrin FXIa 7 TF/FVIIa Thrombin proteolytically inactivates ADAMTS13, preventing destabilisation of the platelet plug + + Fibrin Fibrinogen Prothrombin Thrombin FVa FX FXa FVIIIa FIXa Platelet-plug enhancing role of thrombin TF/FVIIa High MW vWF multimer