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1、SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Thrombosis and Hemostasis,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Classification,vascular disorders platelet disorders disorders of blood coagulation di
2、sorders of anticoagulation system and fibrinolytic system Complex disorders of hemostatic mechanism,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,一、NORMAL HEMOSTASIS GENERAL COMPONENTS,VASCULAR WALL PLATELETS COAGULATION CASCADE,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Mechanisms of Hemostasi
3、s,vascular constriction (neural, myogenic and humoral) formation of a platelet plug; formation of a blood clot as a result of blood coagulation anticoagulation and fibrinolysis as a result of dissolution of the blood clot,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,1、Vascular,SHENGJING HOSPITAL O
4、F CHINA MEDICAL UNIVERCITY,内膜(intima)中膜(media)外膜(advertitia,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,BV Injury,Platelet Activation,Plt-Fusion,Blood Vessel Constriction,Coagulation Activation,Stable He
5、mostatic Plug,Thrombin, Fibrin,Reduced Blood flow,Tissue Factor,Primary hemostatic plug,Neural,2、 Formation of the Platelet Plug,Platelet adhesion: First phase of platelet aggregation Platelet Release. Second phase of aggregation,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Platelet adhesion,Adher
6、e to the damaged vascular wall, such as the collagen fibers in the vascular wall even damaged endothelial wall,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Platelet aggregation,Interaction of Platelets,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,IIb,IIb,First phase of platelet aggregation,ADP r
7、eleased from the damaged tissue the platelet adhere together loosely Reversible aggregation,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Platelet Release,After the first phase (reversible) of aggregation the contractile proteins in the platelet contract forcefully and cause the release of granules
8、 that contain multiple active factors including the ADP and thromboxane A2 (血栓烷A2或血栓素A2,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Second phase of aggregation,ADP and thromboxane A2 in turn act on nearby platelets Cause the platelets to adhere to the originally activated platelets. Irreversible
9、aggregation,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,二、Blood Coagulation Clotting Factors,In both the extrinsic and intrinsic pathways,a series of plasma proteins called blood-clotting factors play major roles. Most of these are inactive forms of
10、proteolytic enzymes. When converted to the active forms,their enzymatic actions cause the successive, cascading reactions of the clotting process,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,General Mechanism of Blood Coagulation,Formation of prothrom
11、bin activator (凝血 酶原激活物) Formation of thrombin (凝血酶) Blood Coagulation,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,激活纤溶系统,Extrinsic Pathway,Intrinsic Pathway,common Pathway,三.Intravascular Anticoagulants Antithrombin III,Present in a concentration of
12、 30mg/dl in the plasma It is a serine protease inhibitor combine with active centers of the clotting factors IIa, VIIa, IXa, Xa and XIIa, blocks the effect of these factors and then inactivates them within a few minutes,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Heparin,Produced by mast cells an
13、d located in connective tissue basophil cells of the blood. A large quantities of the heparin is present in the areas of the liver and lungs. By itself, it has little or no anticoagulant property, but when it combines with antithrombin III, it increases a hundred-fold the effectiveness of antithromb
14、in III thus acts as an anticoagulant. Heparin is widely used in medical practice to prevent intravascular clotting,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Heparin mechanism of action,Heparin,Antithrombin III,Thrombin,Protein C,SHENGJING HOSPITAL
15、OF CHINA MEDICAL UNIVERCITY,endothelium,Protein C,Protein C a,thrombin,TM,APCI,Inactivate Va a,activate Fibrinolysis,endothelium,Protein S,TFPI: tissue factor pathway inhibitor (组织因子途径抑制物,TF,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,a,a,TFPI,Inactivate a、TF、a,a,AT,PROTEIN C,PROTEIN S作用机理,SHENGJ
16、ING HOSPITAL OF CHINA MEDICAL UNIVERCITY,XII,XI,IX,VIII,VII,V,X,AT,凝血酶原,凝血酶,Fibrinogen,Fibrin Clot,血栓调理素,蛋白C,活化的 PC-PS,抑制,抑制,抑制,肝素,Fibrinolysis,The process of liquefaction or lysis of the fibrin is called fibrinolysis,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,XIIa PK,Plasminogen,Plasmin,u-PA t-
17、PA,Fibrin and Fibrinogen,Fibrin Degradation Products (FDP,Fibrinogen SFM Fibrin Plasmin Plasmin Plasmin B1-42 B15-42 D-D A、B、C、H A、B、C、H polymers X、Y、D、E X、Y、D、E X、Y、D、E Fibrin Degradation Products (FDPS,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Lab tests for hemostasis,SHENGJING HOSPITAL OF CH
18、INA MEDICAL UNIVERCITY,Bleeding Time (Duke Method,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Bleeding Time (Duke Method,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Take blood every 30 seconds,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Normal : within 3 minutes,SHENGJING HOSPITAL OF CHINA
19、MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Normal : within 10 minutes,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Activated Partial Thromboplastin Time (APTT,Clotting time from factor XII to fibrin clotintrinsic and common path
20、ways APTT: factor deficiency (VIII, IX, XI, XII) inhibitor (lupus anticoagulant, heparin) APPT : hypercoagulable state Monitoring heparin,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Clinical significance,SHENGJING HOSPITAL OF CHINA MEDICAL UNIVERCITY,Prothrombin Time (PT,Clotting time from factor VII to fibrin clotextrins
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