1、1,Chapter 16.,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
2、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-T
3、F-Ca2+ (on membrane) FIX FIXa TFPI-FXa FVIIIa Ca2+-PL prothrombin (FII) PCI FX Fxa PL-Ca2+ 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 = prote
4、in 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 ur
5、okinase-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 f
6、ibrinclot formation,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 fibrin
7、olytic 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,Hypocoa
8、gulable state,Hypercoagulable state,Unbalance of coagulation-anticoagulation and DIC,extensive activation of clotting factors and platelets,consumption of clotting factors and platelets,hemorrhage,11,Therefore DIC usually associated simultaneously with both hemorrhage and thrombosis. Its clinical pr
9、esentations 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 fact
10、ors 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, cardiovascul
11、ar 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 leukemi
12、a, 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 i
13、njury and release tissue factor (TF) 2) Vascular endothelial cells (VEC) injury3) bacterial endotoxin4) Ag-Ab complex5) Protein hydrolytic enzymes6) Particle or colloid7) Virus and other microbe,14,Section 2.,Pathogenesis of DIC,15,The mechanism of DIC is very complex and remains unclear up to now.
14、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 proces
15、s 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, le
16、ading 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 tissu
17、e 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,Infecti
18、ous, endotoxinemia, Ag-Ab complex, persistent ischemia and hypoxia, acidosis extensive damage of vascular endothelial cells . activating clotting reactions (activating Mo/Mf, PMN, T-lymphocyte release TNF, IL-1, IFN, PAF, C3a, C5a, O2),(2) Vascular endothelial cells injury,releasing TF subendothelia
19、l exposure,platelets adhesion Aggregation and release,19, Activation of Mo/Mf, WBC release TF, lysozymes Malignant tumors release TF, cancer procoagulantHemorrhagic pancreatitis, cancer of pancreas release trypsin (may activate prothrombin directly)Exogenous toxin activate FX, prothrombin or transfe
20、r Fbg to Fbn directly Extensivehemolysis 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, PGI2, ETPlatelet activated TXA2Blood flow(vasoconstriction) or stasis (vasod
21、ilation) 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 mi
22、crothrombus 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 exte
23、nsive 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
24、.,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
25、 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
26、 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 s
27、econdary hypoxia, acidosis, cytokines and free radical.,PLn,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 bleed
28、ing 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 bloodto heart,effective circulation blood volume ,peripheral resistance,heart functio
29、n andcardiac output,29,3. Multiple organs dysfunction (MOD),Perfusion impairment / ischemia-reperfusion injuryactivation 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)Extensi
30、ve 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 sy
31、mptoms 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; Adrena
32、l 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 or
33、gan 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
34、,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 h
35、ypoxia, 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 hemo
36、lytic 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.,
