出血性疾病概述-nankai-2012.ppt

出血性疾病概述 中国医学科学院北京协和医学院血液学研究所血液病医院 杨仁池 止血三要素 血管（内皮细胞） 凝血因子 血小板 血管机制 血管收缩性 血管通透性 血管内皮细胞的促凝作用 血管内皮细胞的抗凝作用 血管内皮细胞的抗纤溶活性 血小板机制 形成血小板血栓 通过花生四烯酸代谢形成血栓素A2等具有强烈收缩血管和诱导血小板聚集的介质 释放 PF3直接参与凝血反应 活化血小板在前激肽释放酶（ PK）和高分子量激肽原（ HK）存在的条件下，直接激活凝血因子XI和XII。 Phases of Hemostasis Vasoconstriction Primary Hemostasis formation of platelet plug Secondary Hemostasis clot formation Thrombus and Antithrombotic Events regulation of thrombus formation and dissolution Vasoconstriction Endothelin release Reflex neurogenic Thrombaxane A2 (released with 1° hemostasis) Primary Hemostasis Platelet Adhesion Platelet Release Platelet Aggregation Formation of platelet plug Platelet Adhesion exposed collagen platelet surface receptors (GpIb) von Willebrand factor Platelet Granules Alpha Granules P-selectin fibrinogen and other clotting factors platelet derived growth factor Dense Granules ADP and ATP histamine serotonin epinephrine Platelet Release Thrombaxane A2 ADP (adenosine diphosphate) vWF and other clotting factors Platelet derived growth factor Platelet Release Platelet Aggregation Thrombaxane A2 and ADP set up autocatalytic reaction TXA2 causes plt aggregation and vasoconstriction ADP causes plt aggregation and change in GpIIbIIIa configuration for fibrinogen bridging Thrombin furthers aggregation and initiates fibrin clot Viscous metamorphosis-irreversibly fused mass of platelets Commonly used drugs affecting primary hemostasis Aspirin blocks cyclooxygenase and synthesis of thrombaxane A2 Clopidogrel (Plavix) blocks ADP GPIIb/IIIa blockers block final common pathway of platelet aggregation—linking of plates via fibrinogen bridges Coagulation Cascade Enzyme (activated coagulation factor) Substrate (proenzyme form of factor) Cofactor (reaction accelerator) Phospholipid complex (assembly site) Extrinsic and Intrinsic Interaction Differences in the Clinical Manifestations of Disorders of Primary and Secondary Hemostasis Evaluation of Hemostasis Clinical History family history previ