Disseminated Intravascular Coagulation(DIC),Department of PathophysiologyShanghai Jiao-Tong University School of Medicine,Blood has a complex mechanism to keep the balance between coagulation and anticoagulation by which blood maintains its fluidity.The process of haemostasis involves spasm of injured vessels, restriction of blood flow, formation of short-term platelet plug to seal minor vessels and formation of strong fibrin clot, at last thrombus formation which closes the wound.The thrombus may be dissolved as soon as the injured vessel has healed in order to restore tissue perfusion.,Introducton,Vessel wall Platelets Coagulation factors,Cellular system: Monocyte/ Macrophage Anticoagulants in plasma（TFPI,AT,heparin co-factor II ） Protein C system Fibrinolytic system,Coagulation & hemostasis,Anticoagulation,Hemostasis,Coagulation Cascade,Protein C system,Plasminogen,Extrinic activators,ECPro-PA,enzymes,t-PA, u-PA,Secretion,Urine（UK，u-PA）Bile（bilokinase）Latex、saliva、tear,Tissue,lung、prostate、uterus,Blood cell,RBC, Platelet,Thrombolytic drugsStreptokinase (SK)Urokinase (UK)rt-PA,Proteolyses fibrinogen, fibronectin , laminin ,thrombospondin；Activates collagenases.,Plasmin,PAI-1,PAI-2,PAI-3,Histidine-rich glycoprotein （HRG）,Intrinic activators,Coagulation,a,a,a,KK,PK,VEC-HK,2-plasmin inhibitor (2-PI)2- macroglobin (2 MG),Fibrinolytic system,Exogenous activators,Haemorrhage or thrombosis will appear when the balance between coagulation and coagulation is disturbed. Inappropriate clotting of blood can obstruct vital organ circulation. Systemic activation of coagulation in its most extreme form is known as disseminated intravascular coagulation (DIC).,Coagulation & anticoagulation imbalance,Disseminated Intravascular Coagulation,Coagulation,Anticoagulation,Balance,Coagulation Fibrinolysis,Exposure of blood to procoagulant substances,Secondary fibrinolysis（FDP formation）,widespread thrombosis,systemic hemorrhagic syndrome,Clotting factors & Platelet depletion,Coagulation Fibrinolysis,Definition of DIC Causes of DIC Pathogenesis of DIC Main Features of DIC,Topics,Definition of DIC,Disseminated intravascular coagulation (DIC) is a complex systemic thrombohemorrhagic disorder involving the generation of intravascular fibrin and the consumption of procoagulants and platelets. The resultant clinical condition is characterized by intravascular coagulation and hemorrhage.,Causes of DIC,The Accepted Disease Entities Generally Associated with DIC,Sepsis/severe infection Malignancy solid and myeloproliferative malignancies Obstetric complications Amniotic fluid embolism, Abruptio placentae Retained dead fetus syndrome Trauma (neurotrauma) ,Organ destruction, Burns Severe hepatic failureRheumatologic illness Adult Stills disease, Lupus Vascular abnormalities Kasabach-Merritt syndrome, Large vascular aneurysmsHemolysis,The diseases which associated with DIC always have one or more triggering factors that can activate clotting factors and intravascular coagulation., Release TF VEC injury LPS Ag-Ab complex,Triggering factors, Protease Microparticles Pathogenic Microbes (viruses),Pathogenesis of DIC,Activation of coagulation Disabled anticoagulant mechanism Impaired fibrinolysis,Activation of coagulation,Tissue damage Endothelial disruption HemolysisLeukemiaOther procoagulant molecules enter the vascular system,HS,TM,collagen,Anticoagulation actions of Endothelial cells,a 、a、T,TF/a、a,TFPI,Thrombin（T）,cleavage of 、,PL,PL aggregation,PC,t-PA,u-PA,PGI2,APC,PAI,Negative charge surface,T endocytosis,Procoagulant activities of injured endothelial cells,Activation of coagulation,PL activation,PAI t-PA,TF vWF,ET,collagen,Fibrin,Thrombin（T）,TF/VIIa,TNF、IL-1、PAF,TXA2 PGI2,FN,FN,VN,WBC,Back,PL adhesion/aggregation,Suppression of anticoagulant pathways,Antithrombin activity is reduced Protein C pathway is incapacitatedTFPI is another anticoagulant mechanism that is disabled,Impaired fibrinolysis,Experimental and clinical studies indicate that during DIC, the fibrinolytic system is largely suppressed at the time of maximal activation of coagulation. This inhibition of fibrinolysis is caused by a sustained rise in the plasma level of plasminogen activator inhibitor-1 (PAI-1), the principal inhibitor of the fibrinolytic system.,Plasminogen,Extrinic activators,ECPro-PA,enzymes,t-PA, u-PA,Secretion,Urine（UK，u-PA）Bile（bilokinase）Latex、saliva、tear,Tissue,lung、prostate、uterus,Blood cell,RBC, Platelet,Thrombolytic drugsStreptokinase (SK)Urokinase (UK)rt-PA,Proteolyses fibrinogen, fibronectin , laminin ,thrombospondin；Activates collagenases.,Plasmin,PAI-1,PAI-2,PAI-3,Histidine-rich glycoprotein （HRG）,Intrinic activators,Coagulation,a,a,a,KK,PK,