1、Chapter 12Coagulation and Anti-coagulation ImbalanceIntroduction:&Coagulation factors Production source Factor I(fibrinogen)Liver Factor II(prothrombin)Liver Factor III(tissue factor)Tissue Factor IV(Ca2+)Factor V Liver Factor(obsolete=factor Va)Factor VII Liver Factor VIII Endothelial cells Factor
2、IX Liver Factor X Liver Factor XI Liver Factor XII Liver Factor XIII Platelets I.Coagulation System and Its FunctionplateletsScanning electron micrograph of moderately active plateletPseudopods thrombosis platelet adhesion platelet aggregation(II):1.Extrinsic Pathway for Blood ClottingTissue factorT
3、issue factorProthrombinProthrombin activator activatorprothrombinprothrombinthrombinthrombinaaaaCaCa2+2+Tissue Tissue damagedamageCaCa2+2+PhospholipidPhospholipid(platelet)(platelet)aaCaCa2+2+fibrinogenfibrinogenfibrinfibrinaa2.FXII:a protease (intrinsic to the blood)FXII converts FXI to FXIa conver
4、ts FIX to FIXa “phospholipids+Ca2+FXa+FVa”complex(prothrombin activator)converts prothrombin to thrombin cleaves fibrinogen into fibrinphospholipidphospholipidIntrinsic Pathway for Blood ClottingfibrinfibrinaaaaaaaaCaCa2+2+aaCaCa2+2+prothrombinprothrombinthrombinthrombinProthrombinProthrombin activa
5、tor activatoraaCaCa2+2+VEC injuryVEC injuryCaCa2+2+fibrinogenfibrinogenplateletplateletAnticoagulant factors Production source TFPI endothelial cell Heparin Liver Antithrombin III(AT-III)Liver Protein C(PC)Liver Protein S(PS)Liver Plasminogen Liver FDPIII.Anticoagulation SystemTissue Factor Pathway
6、Inhibitor(TFPI,组织因子途径抑制物组织因子途径抑制物)CaCa2+2+,Xa,Xa,X,X inactivationinactivation VEC VECTFPITFPITM-Protein C System（血栓调节蛋白（血栓调节蛋白-蛋白蛋白C系统）系统）Antithrombin&Heparin（抗凝血酶（抗凝血酶III，肝素），肝素）Clear thrombin AT-AT-clear IIa，VIIa,IXa XIa,Xa,XIIa AT-AT-heparinheparinX100X100 monocyte-macrophage system&hepatocytecan
7、 clear and remove can clear and remove procoagulants(endotoxin,Ag-Ab procoagulants(endotoxin,Ag-Ab complex,etc)complex,etc)activated coagulation factors activated coagulation factors（TFTF）prothrombinprothrombin activator activator monomer of fibrin monomer of fibrincan activate can activate endogeno
8、us anticoagulation substances endogenous anticoagulation substances fibrinolytic fibrinolytic system system Function dissolving the thrombus that has already formed in vessels III.Fibrinolytic SystemVEC and tissue injuryplasminplasminogenfibrinogenFDPTPA(tissue plasminogen activator)a XIIaplasma pro
9、activator2.anoxia，stasis，tissue damage，and fibrin deposition VEC and tissue injury urokinase and streptokinase：artificial plasminogen activatorssolublecan hydrolyze fibrinogen and many coagulation factorsanticoagulation effect fibrin degradation products,FDP，纤维蛋白降解产物，纤维蛋白降解产物Disseminated Intravascul
10、ar Coagulation,DICI.Concept of DIC DIC is a pathological syndrome characterized by bleeding,Bp or shock,multiple organ dysfunction(embolism)and anemia,which results from the disturbance of kinetic balance of coagulation and fibrinolytic processes(hypercoagulable hypocoagulable).causes extensive acti
11、vation of clotting factors(hypercoagulable state)consumption of clotting factors and platelet,deposition of fibrin and secondary fibrinolysis(hypocoagulable state)bleeding,Bp or shock,multiple organ dysfunction(embolism),anemiaWaterhouse-Friderichsen syndromeadrenal necrosisMeningococcemia(脑膜炎球菌血症脑膜
12、炎球菌血症 on the calves(小腿）小腿）Meningococcemia associated purpura(I)Etiology1.Infection(most common):bacteria and their toxins,fungi,viruses,rickettsiae;tuberculosis,abscesses,osteomyelitis2.Malignancy:acute promyelocytic leukemia,acute monocytic leukemia,disseminated prostatic carcinoma;lung,breast,gast
13、rointestinal malignancy 3.Obstetrical complications:abruption placenta,abortions,amniotic fluid embolism,hemorrhagic shock;dead fetus syndrome4.Trauma&large operation:massive tissue destruction,brain damage,massive burn,organ transplantation5.Vascular disease:brain infarction or hemorrhage;aortic an
14、eurysm,giant hemangioma6.Others:heparin-induced thrombocytopenia with thrombosis(HITT)purpura in newborns(homozygous protein C deficiency)II.Etiology and Pathogenesis of DICleukemia cell injury(II)PathogenesisFIII(tissue factor)release into blood site activity of TF(/mg)liver 10 muscle 20 brain 50 l
15、ung 50 placenta 2000 Q：为什么产妇容易发生：为什么产妇容易发生DIC？severe infection and endotoxemia;severe acidosis;persistent tissue ischemia and hypoxia;strong immune reactions Ag-Ab complex esevere RBC destruction:transfusion of incompatiable blood,acute hemolytic reactionsRBC injury*absorb VII,IX,X and prothrombin t
16、o accelerate coagulation*release of ADP and PF3initiate a platelet release reaction adhesion&aggregation of platelet WBC destruction:acute promyelocytic leukemia,chemotherapy treatment WBC injury a TF-like agent release extrinsiccoagulation triggered bacterial sepsis endotoxin,IL-1,TNF-release extri
17、nsic coagulation triggeredDestruction or activation of platelets:endotoxin,antigen-antibody complex damage platelets release of PF3,PF4,-TG PF3:can accelerate the activation of prothrombin PF4:can neutralize the action of heparin -TG:can promote the coagulation of bloodacute necrotic pancreatitis re
18、lease of trypsin(enzyme)converting prothrombin to thrombinsnake venom activation of FX,FV,prothrombin;conversion of fibrinogen to fibrinmetastatic cancer cells secrete procoagulant substancesamniotic fluid embolism TF-like agent releasetrauma,burns,viruses activation of FX coagulation system(+)Ag-Ab
19、 complex activation of FXII coagulation system(+)bacteria(endotoxins)activation of TF Excessive clottingInfectionCancerChildbirth,dead fetus,or surgerySevere head injuryPoisonous snakeClotting factors and platelets are depletedExcessive bleeding occursEndothelial damage;tissue damage;director activa
20、tion of factor X,damage of blood cellsHypercoagulable stageHypocoagulable stageSecondary fibrinolytic stage III.Precipitating Factors of DICmonocyte-macrophage system:macrophages in and the Experimental study:GSR is a DIC-shock syndrome after two temporally spaced intravenous injection of small dose
21、 of bacterial endotoxins.The injections of endotoxins can block the reticuloendothelialsystem,which can induce DIC.the 1st time:consumption of monocyte-macrophage system the 2nd time:blockade of monocyte-macrophage system,deactivation of endotoxins blood coagultionLiver:clear FIXa,FXa,FXIa,etc.synth
22、esize PC,AT-III,plasminogen,etc.Pregnancy:from 3nd week,Vascular disorders:huge aortic aneurysms,giant hemangiomas（blood flow slow down local activation of coagulation cascadeconsumption of platelet and fibrinogensmokingdiabetesin the terminal stage of pregnancysome drugs(fibrinolytic inhibitors)IV.
23、Stages of DICplatelet and clotting factors consumptionfibrinolytic activity plasmin formationFDP formation 1.:develops rapidly over several hours or l-2 days underlying diseases:septicemia,shock,severe trauma,etc.2.:develops over a period of several days underlying diseases:malignancies,intrauterine
24、 fetal dead,giant hemangiomas,etc.3.:develops and persists over many weeks or months underlying diseases:malignancy,1iver and kidney disease,etc.V.Clinical Classification of DIC decompensated compensated overcompensated clotting consumption consumption consumptionfactors production =production reple
25、tion Depletion=repletion Depletion150(normal150，000/000/L)L).The prothrombin time(PT)was 29 sec(normal,12.5).The level of fibrinogen degradation products was 360-520 g/L(normal,40)and the plasma antithrombin III level was 28%(normal,80-120).Clinical Case-1 Based on these findings,the diagnosis was D
26、IC secondary to severe trauma.Surgical exploration revealed diffuse oozing of blood at the site of the operation,but only partial surgical hemostasis could be achieved.The patient was given supportive treatment with large infusions of fresh plasma and platelet concentrates.The bleeding stopped 48 ho
27、urs later.Coagulation parameters eventually returned to normal and the subsequent clinical course was uneventful.Clinical Case-1 A 23-year woman,induced abortion,delivered one dead fetus.14 hrs after parturition,convulsion and obnubilation developed.Large ecchymosis on extremities and abdomen.After parturition,profluvium sanguis from vagina constantly.BP:undetectable;platelet:7,000;BT:1 min;CT:1min;PT:18 sec;Fib:1.1g/L;3P test(+)Clinical Case-2 Clinical Case-3
