2. Disseminated Intravascular Coagulation (DIC)

3. 【 Change of basic pathology 】 【 Change of basic pathology 】 Key change Key change This fine homeostatic balance of controlled thrombin generation is lost in DIC. DIC represents a continuum in clinical – pathological severity, characterized by the increasing loss of localization or compensated control in intravascular activation of coagulation. It is characterized by the activation of the coagulation system with resultant consumption of a variety of coagulation proteins and platelets, which results in hemorrhagic diathesis and ischemic injury to various tissues. It is characterized by the activation of the coagulation system with resultant consumption of a variety of coagulation proteins and platelets, which results in hemorrhagic diathesis and ischemic injury to various tissues. Concept Concept

5. Prothromboticstate thrombotic state thrombotic state Lowconsumption of coagulationstatus Secondaryfibrinolysis Basic pathological process Basic pathological process Concept Hypercoagulable state Hypocoagulable state Pathological features Pathological features Bleeding 、 Shock 、 MODF 、 Microangiopathic hemolytic anemia

6. 1. Basic disease Condition associated with DIC Cause

7. Infectious disease---the most common clinical condition associated with DIC; Severe trauma---acute DIC is often seen with serious injuries and burns caused by the release of thromboplastic material; Neoplasia---both solid tumor and cancer; Vascular disorder---large aortic aneurysms may result in local activation of coagulation; Obstetric accidents---includes amniotic fluidembolism and placental abruption, the fetus, the placenta, and the amniotic fluid are rich in thromboplastic substances.

8. Normal hematostasis, fibrinolysis and PC system K PK Ⅻ a collagen HK Ⅹ a Ⅻ Ⅻ a TF Ⅺ Ⅺ a Ⅶ a Ⅶ Ca 2+ Ca 2+ Ⅸ Ⅷ Ⅹ Ⅴ ⅩⅢ Ca 2+ Ⅹ a 、Ⅱ a F 1+2 ⅩⅢ a Ⅱ a Ⅱ Ca 2+ FPA/FPB Fbg FM Fbn Intrinsic pathway Extrinsic pathway Ⅹ a Ⅴ a PL+Ca 2+ Ⅸ a Ⅷ a PL+Ca 2+ Blood coagulation Blood coagulationAT TFPI （-）（-）（-）（-） Blood coagulation

9. Monocyte-macrophage Vascular endothelial cell （ VEC ） Anticoagulation factors in plasma AT 、 TFPI Protein C system Fibrinolytic system coagulation inhibitory systems Cell anticoagulation system Body fluid anticoagulation system Blood coagulation

10. excessive generation of thrombin excessive generation of thrombin defects in inhibitors of coagulation defects in inhibitors of coagulation generation of systemic plasmin and fibrinolytic defect generation of systemic plasmin and fibrinolytic defect Pathogenesis of DIC Pathogenesis

11. Trauma 、 Obstetrical calamities 、 Tumours Trauma 、 Obstetrical calamities 、 Tumours Tissue necrosis TF↑↑ Tissue necrosis TF↑↑ Ⅱ a ↑↑abnormal activation of the extrinsic coagulation system Ⅱ a ↑↑abnormal activation of the extrinsic coagulation system ■ Severe tissue injury Fbg Fbn + active platelet Fbg Fbn + active platelet Microthromobus↑↑↑ DIC Microthromobus↑↑↑ DIC Pathogenesis Excessive generation of thrombin

12. 1. Severe tissue injury Introduction into the circulation of substances with tissue thromboplastic activity may initiate the extrinsic clotting reactions. Introduction into the circulation of substances with tissue thromboplastic activity may initiate the extrinsic clotting reactions. This can occur with severe trauma, wounds, major operation, malignant necrosis and by the actions of uterine contents in patients with obstetrical complications. This can occur with severe trauma, wounds, major operation, malignant necrosis and by the actions of uterine contents in patients with obstetrical complications.

13. M  、 PMN activated M  、 PMN activated cytokines, completment, ROS↑ cytokines, completment, ROS↑ ■ Extensive damage of vascular endothelial cells ■ Extensive damage of vascular endothelial cells VEC has the normal anticoagulant effect, damage VEC has a procoagulant effect. VEC has the normal anticoagulant effect, damage VEC has a procoagulant effect. infection, ET, hypoxia, acidosis VEC injury VEC injury TF↑ collagen fibers exposed TF↑ collagen fibers exposed micro-thrombosis Ⅻ a ↑platelet adhesion and aggregation micro-thrombosis Ⅻ a ↑platelet adhesion and aggregation DIC coagulation increased DIC coagulation increased Pathogenesis Direct way Indirect way

14. 2. Extensive damage of vascular endothelial cells 2. Extensive damage of vascular endothelial cells Infection, shock, hypoxia and immune reactions can damage the vascular endothelial cells. Infection, shock, hypoxia and immune reactions can damage the vascular endothelial cells.

15. Blood contacts with exposed collagen to trigger intrinsic clotting cascade through activation of factor Ⅻ and to aggregate platelets. In infection, gram-negative bacterial endotoxin can cause clotting in many animal species and endotoxinemia is a major cause of intravascular clotting.

16. Defects in inhibitors of coagulation Pathogenesis Antithrombin,protein C, and tissue factor-pathway inhibitor appear to be affected in DIC. Plasma levels of AT are markedly reduced as a result of the ongoing coagulation, degradation by elastase released from activated neutrophils. Then the protein C system is impaired. Nature coagulation inhibitors, including AT, protein C, are consumed thus contributing to the increased generation of thrombin and fibrin.

17. Generation of systemic plasmin and fibrinolytic defect Pathogenesis The plasma level of plasminogen-activator inhibitor thpe 1 is increased, which inhibits the fibrinolytic system.

18. Predisposing factors to DIC Inappropriately conditioned monocytes-macrophages Liver injury Hypercoagulable state Dysfunction of microcirculation Predisposing factors

19. Hypercoagulable state of blood Predisposing factors Inappropriately conditioned monocytes-macrophages The reticuloendothelial system can remove most of the products of introvascular coagulation and various initiators of the process from the circulation. The platelets and several kinds of clotting factors (F Ⅰ, Ⅱ, Ⅴ, Ⅶ, Ⅸ, Ⅹ, Ⅻ, etc.) in blood are increased. The activity of anticoagulant materials and or fibrinolysis are decreased.

20. Stasis of the microcirculation permits activated clotting factors to accumulate in blood capillary making it easier to develop into DIC. Stasis of the microcirculation permits activated clotting factors to accumulate in blood capillary making it easier to develop into DIC. Dysfunction of microcirculation Predisposing factors Severe hepatic dysfunction

21. Consequences of DIC Consequences

22. Consequences Bleeding

23. C onsumption of clotting factors and platelets C onsumption of clotting factors and platelets Activation of secondary fibrinolytic system Activation of secondary fibrinolytic system Production of fibrin degradation products Production of fibrin degradation products Bleeding mechanisms Consequences

24. ▲ Microthromobus blood returning to heart ↓ ▲ Microthromobus blood returning to heart ↓ DIC bleeding blood volume↓ DIC bleeding blood volume↓ ▲ Bradykinin,histamine↑ vasodilation blood pressure↓ ▲ Bradykinin,histamine↑ vasodilation blood pressure↓ FDP can increased to dilates vessels that cause hypotension FDP can increased to dilates vessels that cause hypotension ▲ Heart function ↓↓ ▲ Heart function ↓↓ cardiac output↓ cardiac output↓ blood pressure↓ blood pressure↓ Disturbance of circulation---Shock Consequences

25. 肾小 球 肺脏肺脏肺脏肺脏

26. Consequences Microangiopathic hemolytic anemia (MHA)