1、Disseminated Intravascular Coagulation弥散性血管内凝血弥散性血管内凝血What did the baby occur?Dengue Hemorrhagic FeverOutline of ChapterWhat is DIC?How and why does DIC occur?(etiology and pathogenesis)Which factors can influence the development of DICManifestation of clinicPrinciple of prevention and treatmentOver
2、view of hemostatic system1.Overview of haemostatic process1)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 systemFibrinolytic system:Plas
3、minogen,plasmin and their regulatorCoagulation system:12 Except for TF and Ca2+others synthesized by liverWhy does vasospasm occur?What are mechanisms of vasospasm?Vasospasm of injured vesselPlatelets adhere to an injured blood vessel and release chemical factors that cause formation of platelet plu
4、g and contribute to activation of a coagulation cascadeLead to a mount of thrombinFibrin thrombusPlasminogen activatorsPlasminogenPlasminFibrin disgested,blood flow restoredTwo counteracting phases of hemostasis:blood coagulation and fibrinolysis(1)Extrinsic pathway(Tissue factor pathway)(2)Intrinsi
5、c 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 adhesionPlatelet aggregation GPb/a
6、 multivalent binding fibrin Platelet secretion ADP,TXA2 are important for aggregation of platelet.Interlinked and promoted each otherExtrinsic IntrinsicStable Fibrin clotGranule-ADP,TXA2,Serotonin etc Granule-Fibrinogen,factors,TGF-,TGF-Anticoagulation System 1)Monocyte-macrophage system：cleaning ou
7、t the clotting factors 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-TFTissue factor Pathway inhibitor:Main produced by Vascular ECs（3）Protein C system Protein C(P
8、C)、Protein S and thrombomodulin（TM）Pathway of anti-coagulation：(1)Inhibit a、a(2)Block Fa combined with platelet(3)Increase fibrinolysis PAI-1PAProtein C systemPCPS-cofactorTM(thrombomodulin)+thrombinactivatefibrinolytic system Plasminogen PLgPlasmin PLnPlasmin Activator Extrinsic:PA,t-PA,u-PA;Intrin
9、sic:thrombin,a,a,and kallikrein Exogenous:Streptokinase,Staphylokinaseplasminogen-activator inhibitor 1(PAI)2-antiplasmin and 2-macroglobulin.Thrombin activatable fibrinlysis inhibitor(TAFI)Role of endothelial cells AT/Heparins/HeparinsTFPITM/ThrombinPCAPCAPC/PSMechanism of coagulation and anticoagu
10、lationDefinition of DICEtiological factorWidespread intravascular activation of coagulationIntravascular thrombus(fibrin)formation.Bleeding,Anemia,Shock,Organ dysfunction Type Diseases Infection Disease Gram-negative or Gram-positive sepsis,viral hemorrhagic fever,viral hepatitisMalignancy Solid tum
11、ors,acute leukemia Obstetric conditions Preeclampsia,placental abruption,amniotic fluid embolism,caesarean birth,abortion,Trauma Physical force,burns,brain trauma,surgical operationsSevere allergic/toxic reactions Snake biteSevere immunologic reactions Transfusion reaction Disorders associated with
12、DIC Pathogenesis(1)The tissue factor and systemic activation of coagulation TF-VIIa complex The extrinsic pathway be activated(2)Endothelial injury and imbalance of procoagulation and anticoagulationanoxia,severe infections and endotoxin Endothelial lesionTF or TNFa,IL-1,IL-6 Degradation of TM/PC an
13、d 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)Blood cells damage(3)Entrance of procoagulant substances to bloodsnake venom,
14、cancer,pancreas protease1)Red blood cell(RBC)damage ADP activate platelet phospholipid of cell membrane2)White blood cells(WBC)damage and activation TF-pathway,TNF IL-1,IL-6Anti-coagulationProcoagulationFactors influence the development of DIC (1)Mononuclear phagocyte system dysfunction(2)Liver dysf
15、unction (3)Hypercoagulable state (4)Microcirculation dysfunction soluble tissue factor,endotoxin,thrombin soluble complexes of fibrin monomersEndotoxin low doseShwartzman reaction 24hSecond injectionDICMononuclear phagocyte cleanClearing activated factors IX,X and XIReplenish coagulation factors,pla
16、sminogen,2-antiplasmin,ATIII and PC DICCoagulation 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)DICaccumulation of procoagulants and increases susceptibility to platelet adherence and aggregation.acidosis tissu
17、e anoxia and endothelial lesion Giant hemangioma(巨型血管瘤)Susceptibility to DICClinical classification of DIC(1)Acute DIC:Several hours or 1-2 days Severe Infection(septic shock),Traumatic Shock,Incompatible Blood Transfusion etc.(2)Subacute DIC:Over a period of some days.Malignacies,Retained Dead Fetu
18、s 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 hemangioma etc.Stage of DICDepleted Hypocoagulable stageCharacte
19、ristic:thrombin and coagulants dcrease;fibrinolytic system activation blood present hypocoagulablebleedingHypercoagulable stageCharacteristic:more thrombin,microthrombus and blood present hyper-coagulable statusSecondary fibrinolytic stageCharacteristic:more plasmin and anticoagulation increase and
20、present obvious bleeding Alterations of metabolism and function (1)Bleeding(2)Organ dysfunction(3)Shock(4)Haemolytic anemias Mechanisms of bleeding1)Consumption of coagulation factors and platelets PlasminFXFY+FDFD+FEFDPFbn(Fbg)3)Formation of fibrin degradation products(FDP)2)Activation of the fibri
21、nolytic 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 plateletFDP test：3P test(plasma protamin paracoagulation test)D-dimer：Index of DIC How to detect hyperfibrinolysis in clinic?(Plasma
22、protamin paracoagulation test)fibrinogenthrombinFibrin(M)fibrinplasminFX+FY+FD+FEFX.M(soluble complex)protaminFXMAuto-aggregationFlocculent precipitate3P test principle(2)Organ dysfunction Kidney：lung：liver：Digestion system：adrenal gland：Waterhouse-Friderichsen syndromepituitary：Sheehans syndromeNer
23、ve 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 anemia 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 brokenPathophysiological Basis of Prevention and Treatment (1)Management of the underlying disorder (2)Improving the microcirculation (3)Reconstructing the balance of coagulation and fibrinolysis
