DIC弥散性血管内凝血课件

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,1,Disseminated intravascular,coagulation,2,Intravascular,Extravascular,Normal circulation Hemostasis,liquidity solidity,( coagulation),Normal,Normal,Blood,Abnomal Abnomal,solidity,(coagulation) liqidity,Thrombotic disease Hemorrhagic,disease,Intravascular,Extravascular,3,?,The function of coagulation system,(Extrinsic, Intrinsic pathway and platelet),?,The function of anticoagulation,(TFPI, PC system, ATIII and fibrinolytic system),?,The regulation of balance by VEC,The key factors,for balance of coagulation-anticoagulation,:,4,The chain reaction of blood coagulation,FXI,FXIa FVII/FVIIa-,TF,-Ca,2+,(on membrane), ,FIX FIXa,TFPI-FXa,FVIIIa Ca,2+,-PL,prothrombin,(FII),PCI,FX Fxa PL-Ca,2+,Fva,APC,(PS),XIII,thrombin,TM-on-VEC,XIIIa,ATIII,PC,Fbn Fbn FM Fbg,(FI),(cross-linked) (soluble),TF = tissue factor; TFPI = TF pathway inhibitor;,Fbg = fibrinogen; Fbn = fibrin; FM = fibrin monomer;,PC = protein C; APC = activated PC; PS = protein S; PCI = PC inhibitor,ATIII = antithrombin III; TM = thrombomodulin; VEC = vascular EC,5,The,fibrinolysis system,Plasminogen (PLg),(Extra-activating pathway),(Intra-activating pathway),tissue-type plasminogen,activation of clotting system,activator (t-PA),XIa,urokinase-type plasminogen,thrombin,activator (u-PA),XIIa XII,(,Exogenous activator),urokinase(UK),kallikrein (KK),streptokinase (SK ),prekallikrein(PK),Plasmin (Pln),Fbg Fbn FDP,(,fibrinogen) (fibrin) (Fbg/Fbn degradation products),6,Inhibit,Xa,VIIa,TF,Inhibit platelet,aggregation,Fibrinolysis,Prevent fibrin,clot formation,Trauma,Adrenalin,Thrombin,ADP,NO, PGI,2,Xa, IIa,Plasmin,Plasminogin,Activators,t-PA, u-PA,Inactivate,Va,VIIIa,PS,Thrombin,PC APC,?,TM,Inhibit,Xa, IIa,AT III,+,Heparin,TFPI,Anticoagulant function of endothelial cells,7,Section 1.,Concept and causes of DIC,8,Todays Question,Question 1. What is DIC?,9,1. Concept of DIC,Disseminated,intravascular,coagulation,(DIC),A syndrome,that results from the disturbance of kinetic balance of,coagulation and fibrinolytic processes.,Characterized,by,extensive intravascular microthrombosis and impairment,of hemostasia.,Its,initial,link,is,activation,of,clotting,system,in,the,body,10,extensive microthrombin extensive,hemorrhage,organ dysfunction Shock aneamia,Normal balance of coagulation-anticoagulation,Hypocoagulable state,Hypercoagulable state,Unbalance of coagulation-anticoagulation and DIC,extensive activation,of clotting factors,and platelets,consumption,of clotting,factors and platelets,secondary fibrinolysis,hemorrhage,organ dysfunction Shock aneamia,11,Therefore DIC usually associated simultaneously with both,hemorrhage,and,thrombosis.,Its,clinical,presentations,include:,1),extensive,hemorrhage,at,skin,mucosa,and,internal,organs,(viscera);,2),shock,;,3),organ,dysfunction,;,4),aneamia.,An,extensive activation of coagulation process,caused by the,entering of coagulation-promoting substances into circulation,An,increased consumption of clotting factors and platelets,deposition of fibrin,and,secondary fibrinolysis,.,results in,12,2.,Causes of DIC,including:,infectious diseases, extensive tissue injury, obstetric,complications, malignant tumors, acute leukemia, shock,hepatic and renal diseases, collagen disease, metabolic,diseases, cardiovascular diseases, intravascular hemolysis,Etiologic Disease of DIC,Diseases or pathologic process which may lead to DIC,Triggering,Factor,Any factors which may trigger or promote DIC occur,13,including:,infectious diseases, extensive tissue injury, obstetric,complications, malignant tumors, acute leukemia, shock,hepatic and renal diseases, collagen disease, metabolic,diseases, cardiovascular diseases, intravascular hemolysis,2.,Causes of DIC,Triggering,Factor,Any factors which may trigger or promote DIC occur,Etiologic Disease of DIC,Diseases or pathologic process which may lead to DIC,1) Tissue injury and release tissue factor (TF),2) Vascular endothelial cells (VEC) injury,3) bacterial endotoxin,4) Ag-Ab complex,5) Protein hydrolytic enzymes,6) Particle or colloid,7) Virus and other microbe,14,Section 2.,Pathogenesis of DIC,15,The,mechanism,of,DIC,is,very,complex,and,remains,unclear,up,to,now.,The,common,pathogenic,process,include,:,1),Triggering,clotting,activation,producing,numerous,insoluble,fibrin,(Fbn),and,activating,platelets;,2),The,generated,Fbn,deposit,in,microvessels,and,is,more,than,hydrolytic,ability,of,fibrinolysin;,3),Alteration,of,fibrinolysis,function,during,the,DIC,process,which,is,related,to,the,pathologic,process,of,micro-thrombosis,and,bleeding,tendency.,16,1. Activation of clotting system,As,soon,as,activation,the,clotting,response,will,be,magnified,by,cascade,or,limited,by,negative,feedback.,The,clotting,system,is,liable,to,be,activated,in,the,microvessels,leading,to,micro-thrombus,formation.,The,causes,and,pathogenesis,of,clotting,system,activation,including:,(1),Tissue,injury,(2),Vascular,endothelial,cells,injury,(3),Other,pathway,to,activate,clotting,system,17,(1) Tissue injury,Severe trauma, burns, surgical operation, obstetric accident,tumor tissue necrosis or metastasis,blood cell injury (radiation or chemical therapy for leukemia),Excessive destruction of tissue,Numerous TF entering the blood,Activating clotting reactions,Besides,lysozymes,released,by,lysosome,of,damaged,cells,may,also,promote,the,activation,of,clotting,system.,18,Infectious, endotoxinemia, Ag-Ab complex,persistent ischemia and hypoxia, acidosis,extensive damage of vascular endothelial cells,.,activating,clotting,reactions,(activating Mo/M,f,PMN, T-lymphocyte, release TNF, IL,-1, IFN, PAF, C,3a, C5a, O,2,),(2) Vascular endothelial cells injury,releasing TF subendothelial exposure,platelets adhesion,Aggregation,and release,19,Activation,of,Mo/M,f,WBC,release,TF,lysozymes,Malignant,tumors,release,TF,cancer,procoagulant,Hemorrhagic,pancreatitis,cancer,of,pancreas,release,trypsin,(may,activate,prothrombin,directly),Exogenous,toxin,activate,FX,prothrombin,or,transfer,Fbg,to,Fbn,directly,Extensive,hemolysis,release,ADP,activate,platelets,release,erythrin,TF-like,effect,(3) Other pathway to activate clotting system,20,2. Change of vasomotorial activity and,blood fluidity,VEC injury,?,EDRF,PGI,2,ET,Platelet activated,?,TXA,2,Blood flow,(vasoconstriction) or,stasis,(vasodilation),eliminate of coagulant or activate clotting factors,PAF,histamin,BK,?,vascular,permeability,(BK:,bradykinin),Deposit of Fbn,Blood condense, Viscosity,21,3. Disturbance of fibrinolysis,(1),Local,fibrinolysis,clotting,VEC,injury,local,anticoagultive,and,fibrinolytic,function,deposit,of,Fbn,microthrombus,formation,(2),Secondary,fibrinolysis,bleeding,FXIa,thrombin,KK,etc.,promote,transfer,PLg,to,PLn,VEC,release,t-PA,u-PA,transfer,PLg,to,PLn,Protein,C,activated,by,thrombin,(via,VEC-TM),form,activated,protein,C,(APC),anticoagulation,and,promote,fibrinolysis.,22,Pathological Factors,extensive activation of clotting factors and platelets,intravascular coagulation,consumption of clotting secondary,factors and platelets fibrinolysis,extensive hemorrhage,aneamia shock organ dysfunction,(Disseminated intravascular coagulation, DIC),Hypercoagulable,state,Hypocoagulable,state,23,Section 3.,Primary,clinical,presentations,of DIC,24,DIC,may,lead,to,four,consequences,as,follows:,1.,Disturbance,of,coagulation,-,Bleeding,2.,Disturbance,of,microcirculation,-,Shock,3. multiple organs dysfunction -,MOD,4.,Microangiopathic,hemolytic,-,Anemia,25,1. Disturbance of coagulation-Bleeding,The,prime,and,common,symptom,of,DIC,is,bleeding.,The,features,of,bleeding,in,DIC,:,(1),High,occurrence,rate,(7080%),(2),Difficult,to,explain,by,primary,disease,(3),Manifold,bleeding,types,(4),Difficult,to,be,cured,by,regular,hemostatics,26,The,causes,of,bleeding,in,DIC,including:,(1),Excessive,consumption,of,coagulation,substances,(clotting,factors,and,platelets);,(2),Secondary,enhance,of,fibrinolysis,(3),Anticoagulative,effects,of,fibrin,degradation,products;,Fbg,/,Fbn,FDP(fragment,X,Y,E,D),X,Y,+,FM,soluble,fibrin,monomer,complex,(SFMC),(4),Injury,of,capillary,wall,caused,by,primary,cause,of,DIC,and,secondary,hypoxia,acidosis,cytokines,and,free,radical.,PLn,Thrombin,Fbg,(FI),FM sFbn Fbn,27,DIC,especially,acute,DIC,is,often,associated,with,shock,Shock,in,sever,degree,or,in,late,stage,can,also,promote,the,production,of,DIC,2. Dsturbance of microcirculation -,shock,28,(1),Extensive,microthrombus,formation,(2) Extensive bleeding,permeability,?,plasma exudation,(3) Activating kinin, histamin,?,shock,microvessel dilation,(4) FDP (A,B,C),(5),Microthrombus,coronary perfusion,?,pulmonary,hypertension,cardiac,load,?,Ischemia,hypoxia&,acidosis,returned blood,to heart,?,effective circulation,blood volume,?,peripheral resistance,?,heart function and,cardiac output,?,29,3. Multiple organs dysfunction (MOD),Perfusion impairment,/,ischemia-reperfusion injury,activation of WBC,/,inflammatory mediator,Ischemic tissue damage,MOD,MOD is usually the most important cause of death in DIC.,30,Occurrence of MOD is related to following factors:,(1),Extensive microthrombi formation in the organs, ischemia, hypoxia, impairment of metabolism and,function, or even necrosis and organ failure.,(2),Pathologic alteration caused by effects of organs each,other,DIC,?,Lungs,?,pulmonary circulation,?,Heart,hypoxia, acidosis,?,Other organs,(3) Pathologic alteration and symptoms of primary,diseases,(which should be rule out from MOD).,inflammation of the lungs,?,dysfunction of respiration,s,e.g.,Lung,ARDS,;,kidney,ARF,;,Digestive system nausea, vomiting, diarrhea, hemorrhage;,Liver,jaundice,and,hepatic,failure;,Heart,CO,PAWP,;,Pituitary,necrosis,Sheehans,syndrome;,Adrenal,cortex,hemorrhagic,necrosis,Waterhouse,-friderchsens,syndrome;,CNS,bleeding,edema,(somnolence,coma,convulsion),31,Occurrence of MOD is related to following factors:,(1),Extensive microthrombi formation in the organs, ischemia, hypoxia, impairment of metabolism and,function, or even necrosis and organ failure.,(2),Pathologic alteration caused by effects of organs each,other,DIC,?,Lungs,?,pulmonary circulation,?,Heart,hypoxia, acidosis,?,Other organs,(3) Pathologic alteration and symptoms of primary,diseases,(which should be rule out from MOD).,inflammation of the lungs,?,dysfunction of respiration,s,32,Occurrence of MOD is related to following factors:,(1),Extensive microthrombi formation in the organs, ischemia, hypoxia, impairment of metabolism and,function, or even necrosis and organ failure.,(2),Pathologic alteration caused by effects of organs each,other,DIC,?,Lungs,?,pulmonary circulation,?,Heart,hypoxia, acidosis,?,Other organs,(3) Pathologic alteration and symptoms of primary,diseases,(which should be rule out from MOD).,inflammation of the lungs,?,dysfunction of respiration,33,4. Microangiopathic hemolytic anemia,RBC,may,damaged,as,they,move,through,the,fibrin,net,and,result,in,a,striking,hemolytic,anemia,with,a,special,morphologic,abnormality,of,the,RBC,called,schistocyte,.,(Twisted,cells,crenated,cells,triangular,cells,helmet-,shaped,cells,and,microspherocytes,),The,hemolysis,can,provide,more,triggering,material,(ADP,and,membrane,phospholipid),for,continued,intravascular,coagulation.,34,Section 4.,Factors influencing the,development of DIC,35,?,Mononuclear phagocyte system dysfunction,?,Severe dysfunction of the liver,?,Hypercoagulable state,?,Disorder of microcirculation,?,Fibrinolytic system,dysfunction,36,Prolonged,and,excessive,Repeated,infection,administration,of,glucocorticoid,hormones,Severe,hepatic,disease,Impairing Mo/M,f,system function,Disable,to,clean,clot-promoting,substances,(Fbg,Fbn,FM,and,FDP,etc.),Generalized Shwartzman reaction, GSR,(1) Mononuclear phagocyte system dysfunction,37,(2),Severe dysfunction of the liver,1),Pathogenic,factors,of,liver,disease,such,as,virus,Ag-Ab,complex,and,some,drugs,may,activate,clotting,system.,2),Acute,hepatic,necrosis,may,release,TF,and,lysozymes,3) Decreased ability of production and elimination of,clotting and anticoagulative factors.,38,Primary:,genetic,ATIII,PC,PS,deficiency,etc.,Secondary:,nephrotic,syndrome,malignant,tumors,leukemia,toxemia,of,pregnancy,etc.,(3),Hypercoagulable state,39,1),VEC,injury,Activation,of,clotting,system;,2),Blood,flowor,stasis,accumulation,of,activated,clot,factors;,3),Dysfunction,of,liver,kidney,ability,of,eliminate,clot,factors,and,fibrinolytic,products,?,4),Vasomotorial,impairment,feasible,to,Fbn,deposit,and,microthrombi,formation.,(5),Fibrinolytic,system,dysfunction,e.g. senility, smoking, late stage of pregnancy, diabetes,misuse of fibrinolytic inhibitor,etc.,(4),Disorder of microcirculation,40,Section 5,Stages and types of DIC,41,1. Stages of DIC,Pathophysiology,Clinical,Laboratory,findings,(1)Hypercoagulable,stage,(2)Consuming,hypocoagulable,stage,(3)Secondary,fibrinolytic,Stage,Exessive activation of clotting factors,and formation of microthrombin,Increased consumption,of,clotting factors and platelet,Considerable formation,of plasmin and FDP,42,1. Stages of DIC,Pathophysiology,Clinical,Laboratory,findings,(1)Hypercoagulable,stage,(2)Consuming,hypocoagulable,stage,(3)Secondary,fibrinolytic,Stage,Hypercoagulable,Bleeding,Bleeding markedly,43,1. Stages of DIC,Pathophysiology,Clinical,Laboratory,findings,(1)Hypercoagulable,stage,(2)Consuming,hypocoagulable,stage,(3)Secondary,fibrinolytic,Stage,Shortened clotting and recalcification,time; Increased adherence of platelet,Prolonged clotting and recalcification time,Reduction of platelet count and Fbg narkedly,Shortened CLT, ELT; Prolonged TT 3P,test (+), Increased FDP,CLT = clot-lysis time,ELT = euglobulin-lysis time,TT = thrombin time,44,Production of FDP and 3p test,(,plasma protamine paracoagulation test),Fibrinogen,Thrombin,Fibrin monomer,(FM),Fibrin polymer,Plasmin,XIIIa,FDP-X,Y,D,E,Stabilized fibrin,( blood clotting ),X + FM soluble fibrin monomer complex (SFMC),Protamin,SFMC X + FM blood clotting,45,Develop,time,Common,causes,Clinic,feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,a few hours to days,within days to weeks,months,46,Develop,time,Common,causes,Clinic,feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,malignant tumors collagenosis,metastasis of malignant,tumors; retained dead fetus,severe infection or trauma,ammiotic fluid embolism,47,Develop,time,Common,causes,Clinic,feature,2. Types of DIC,According to the rate of development, divide into 3 types,Acute,Subacute,Chronic,mild or concealed,microthrombin formation,bleeding,shock, blooding,exacerbate rapidly,48,:,According,to,compensatory,state,divide,into,3,types,Clotting,factors,and,platelet,Clinical,situations,compensatory,Consumption = production,discompensatory,Consumption production,over compensatory,Consumption production,49,:,According,to,compensatory,state,divide,into,3,types,Clotting,factors,and,platelet,Clinical,situations,compensatory,Mild DIC,discompensatory,Acute DIC,over compensatory,Chronic DIC or recovery,50,Section,6.,Principles of prevention and,treatment of DIC,51,1.,Pathophysiology,bases,of,diagnosis,of,DIC,(1),Existence,of,causative,diseases;,(2),Existence,of,characteristic,symptoms,and,signs,of,DIC,(3),Positive,laboratory,findings:,platelet,count,Fbg,PT,&,TT,3P,test,(+),CLT,&,ELT,52,2. Pathophysiology bases of prevention,and treatment of DIC,(1),Earlier,diagnosis,and,treatment,(2),Treatment,of,the,causative,disease,(3),Anticoagulation,treatment,(to,block,the,vicious,cycle,of,clotting,response),(4),Protection,of,organ,function,(5),Supplement,of,fresh,blood,or,plasma,concentrated,platelet,or,clotting,factors,(to,recover,coagulation-,anticoagulation,balance),(6),Antifibrinolysis,treatment,Back to cover next chapter,53,A syndrome resulting from the disturbance balance of,coagulation and fibrinolytic processes, characterized by,extensive intravascular microthrombosis and impairment of,hemostasia, is called disseminated intravascular coagulation.,Diseases or pathologic process which may lead to DIC are,called etiologic disease of DIC. Any of them is usually trigger,or promote DIC through one or several factors, which are,called triggering factor.,Summary,54,extensive hemorrhage at skin, mucosa and internal organs,The,pathogenesis,of,DIC,are:,1),Activation,of,clotting,system,(tissue,and,VEC,injury),2) Change of vasomotorial activity and blood fluidity;,3) Disturbance of fibrinolysis,The,clinical,presentations,of,DIC,include:,1),;,2),;,3),;,4),.,Summary,Disturbance of microcirculation (shock),Multiple organs dysfunction (MOD),Microangiopathic hemolytic anemia,55,Following factors may influence the development of DIC:,1),Impairment,of,function,of,mononuclear-macrophage;,2) Severe dysfunction of the liver;,3),Hypercoagulable state;,4),Disorder of microcirculation;,5) Dysfunction of fibrinolytic system,Pathophysiology,basis,of,diagnosis,of,DIC:,1),Causative,diseases;,2),Characteristic,symptoms,and,signs,of,DIC;,3),Positive,laboratory,findings,Summary,56,5,?,Question 3,Explain the relationship,between,SHOCK,and,DIC,57,5,SHOCK,DIC,?,Blood,flow,slow,down,blood,concentrated,RBC,and,platelet,aggregation,blood viscosity,Vascular ECs injury,Severe,acidosis,Monocyte and endothelium releasing TF,Septic Shock: bacteria and toxin,Tissue,releasing,TF,Traumatic,shock,58,5,SHOCK,DIC,?,Returned blood to heart,?,blood concentrated, RBC and platelet aggregation, blood viscosity,Effective circulation blood volume,Extensive bleeding, permeability,?, plasma exudation,Peripheral resistance,?,kinin, histamin,?,microvessel dilation,Heart function and cardiac output,?,pulmonary hypertension, Ischemia, hypoxia& acidosis,