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1、Disseminated Intravascular Coagulation,弥散性血管内凝血,What did the baby occur?,Dengue Hemorrhagic Fever,Outline of Chapter,What is DIC?,How and why does DIC occur?(etiology and pathogenesis),Which factors can influence the development of DIC,Manifestation of clinic,Principle of prevention and treatment,Ov
2、erview of hemostatic system,1.Overview of haemostatic process,Component of hemostasis Keep fluidity,capacity of coagulation Components:vessel wall,platelets,coagulation factors,Anti-coagulation and Fibrinolytic factors.,Anti-Coagulation factors:Cellular system and soluble system,Fibrinolytic system:
3、Plasminogen,plasmin and their regulator,Coagulation system:12 Except for TF and Ca2+others synthesized by liver,Why does vasospasm occur?,What are mechanisms of vasospasm?,Vasospasm of injured vessel,Platelets adhere to an injured blood vessel and release chemical factors that cause formation of pla
4、telet plug and contribute to activation of a coagulation cascade,Lead to a mount of thrombin,Fibrin thrombus,Plasminogen activators,Plasminogen,Plasmin,Fibrin disgested,blood flow restored,Two counteracting phases of hemostasis:blood coagulation and fibrinolysis,(1)Extrinsic pathway(Tissue factor pa
5、thway),(2)Intrinsic pathway,(3)Formation of platelet plug,Platelet activation Collagen,thrombin,ADP,TXA2,epinephrine,serotonin,arginine vasopressin etc.,Platelet adhesion change from smooth disks to spiny spheres and exposing receptor on its surface.GPb binding vWF mediating platelets adhesion,Plate
6、let aggregation GPb/a multivalent binding fibrin,Platelet secretion ADP,TXA2 are important for aggregation of platelet.,Interlinked and promoted each other,Granule-ADP,TXA2,Serotonin etc Granule-Fibrinogen,factors,TGF-,Anticoagulation System,1)Monocyte-macrophage system：cleaning out the clotting fac
7、tors such as tissue factor,prothrombinase and fibrin monomers 2)Soluble system:（1）Antithrombin III(ATIII)、heparin VIIa,a,a,Xa,thrombin,(2)Tissue factor pathway inhibitor(TFPI)Xa-TFPI-VIIa-TF,Tissue factor Pathway inhibitor:Main produced by Vascular ECs,Inhibit a、a(2)Block Fa combined with platelet(3
8、)Increase fibrinolysis,fibrinolytic system,Plasminogen PLgPlasmin PLnPlasmin Activator Extrinsic:PA,t-PA,u-PA;Intrinsic:thrombin,a,a,and kallikrein Exogenous:Streptokinase,Staphylokinaseplasminogen-activator inhibitor 1(PAI)2-antiplasmin and 2-macroglobulin.Thrombin activatable fibrinlysis inhibitor
9、(TAFI),Role of endothelial cells,AT/Heparins,TFPI,TM/Thrombin,PC,APC,APC/PS,Mechanism of coagulation and anticoagulation,Definition of DIC,Etiological factor,Widespread intravascular activation of coagulation,Intravascular thrombus(fibrin)formation.,Bleeding,Anemia,Shock,Organ dysfunction,Type Disea
10、ses Infection Disease Gram-negative or Gram-positive sepsis,viral hemorrhagic fever,viral hepatitisMalignancy Solid tumors,acute leukemia Obstetric conditions Preeclampsia,placental abruption,amniotic fluid embolism,caesarean birth,abortion,Trauma Physical force,burns,brain trauma,surgical operation
11、sSevere allergic/toxic reactions Snake biteSevere immunologic reactions Transfusion reaction,Disorders associated with DIC,Pathogenesis,The tissue factor and systemic activation of coagulation,(2)Endothelial injury and imbalance of procoagulation and anticoagulation,anoxia,severe infections and endo
12、toxin Endothelial lesion,TF or TNFa,IL-1,IL-6,Degradation of TM/PC and HS/AT-III system Down-regulation of tissue factor pathway inhibitor(TFPI)t-PA release decreasePAI-1 release increaseNO,PGI2 and ADP enzyme platelet adherence and aggregation,(-),collagen exposure,(+),intrinsic pathway,(+),HK,(4)B
13、lood cells damage,(3)Entrance of procoagulant substances to blood,snake venom,cancer,pancreas protease,Red blood cell(RBC)damage ADP activate platelet phospholipid of cell membrane,2)White blood cells(WBC)damage and activation TF-pathway,TNF IL-1,IL-6,Factors influence the development of DIC,(1)Mono
14、nuclear phagocyte system dysfunction(2)Liver dysfunction(3)Hypercoagulable state(4)Microcirculation dysfunction,soluble tissue factor,endotoxin,thrombin soluble complexes of fibrin monomers,Endotoxin low dose,Shwartzman reaction,24h,Second injection,DIC,Mononuclear phagocyte clean,Clearing activated
15、 factors IX,X and XIReplenish coagulation factors,plasminogen,2-antiplasmin,ATIII and PC,DIC,Coagulation factors(I,II,V,VII,IX,X,XII),ATIII,t-PA,u-PA,Placental abruption and Amniotic fluid embolism,Placental tissue:PAI and Thromboplastin(TF),DIC,accumulation of procoagulants and increases susceptibi
16、lity to platelet adherence and aggregation.,acidosis,tissue anoxia and endothelial lesion,Giant hemangioma(巨型血管瘤),Susceptibility to DIC,Clinical classification of DIC,Acute DIC:Several hours or 1-2 days Severe Infection(septic shock),Traumatic Shock,Incompatible Blood Transfusion etc.,(2)Subacute DI
17、C:Over a period of some days.Malignacies,Retained Dead Fetus Syndrome etc.,(3)Chronic DIC:Develop and persist over many weeks or months and erupt into hemorrhagic or thromboembolic episode malignancy,Liver Diseases,Connective Tissue Disorders Glomerulonephritis,Lupus Nephritis and Proliferative hema
18、ngioma etc.,Stage of DIC,Depleted Hypocoagulable stageCharacteristic:thrombin and coagulants dcrease;fibrinolytic system activation blood present hypocoagulable,bleeding,Hypercoagulable stageCharacteristic:more thrombin,microthrombus and blood present hyper-coagulable status,Secondary fibrinolytic s
19、tageCharacteristic:more plasmin and anticoagulation increase and present obvious bleeding,Alterations of metabolism and function,(1)Bleeding(2)Organ dysfunction(3)Shock(4)Haemolytic anemias,Mechanisms of bleeding,1)Consumption of coagulation factors and platelets,Plasmin,FX,FY+FD,FD+FE,FDP,Fbn(Fbg),
20、3)Formation of fibrin degradation products(FDP),2)Activation of the fibrinolytic system,FDP anti-coagulation：,1.Block fibrin monomer cross-linked coagulation(X,Y,D),2.Inhibit the formation and action of thrombin(Y,E),3.Inhibit accumulation of platelet,FDP test：3P test(plasma protamin paracoagulation
21、 test)D-dimer：Index of DIC,How to detect hyperfibrinolysis in clinic?,(Plasma protamin paracoagulation test),fibrinogen,thrombin,Fibrin(M),fibrin,plasmin,FX+FY+FD+FE,FX.M(soluble complex),protamin,FX,M,Auto-aggregation,Flocculent precipitate,3P test principle,(2)Organ dysfunction,Kidney：lung：liver：D
22、igestion system：adrenal gland：Waterhouse-Friderichsen syndromepituitary：Sheehans syndromeNerve system：Multiple organ dysfunction,(3)Shock:DIC and shock are in relation of causation each other,(4)Haemolytic anemia,microangiopathic hemolytic anemiaThe characteristic of microangiopathic hemolytic anemi
23、a is schistocyte in blood smear,morphology of schistocyte are helmets,triangular and kite-shaped.fibrin strand form meshwork in microvascularMember of RBC become crisp,so it is easy broken,Pathophysiological Basis of Prevention and Treatment,(1)Management of the underlying disorder(2)Improving the microcirculation(3)Reconstructing the balance of coagulation and fibrinolysis,
