Disseminated Intravascular Coagulation DIC Concept DIC represents a

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Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation (DIC)

Concept DIC represents a continuum in clinical – pathological severity, characterized by the increasing

Concept 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. 【Change of basic pathology 】 Key change This fine homeostatic balance of controlled thrombin generation is lost in DIC.

Concept Basic pathological process Hypercoagulable state Hypocoagulable state Secondary fibrinolysis Low consumption of coagulation

Concept Basic pathological process Hypercoagulable state Hypocoagulable state Secondary fibrinolysis Low consumption of coagulation status thrombotic state Prothrombotic state Pathological features Bleeding、Shock、MODF、Microangiopathic hemolytic anemia

Cause Condition associated with DIC 1. Basic disease

Cause Condition associated with DIC 1. Basic disease

l l l Infectious disease---the most common clinical condition associated with DIC; Severe trauma---acute

l l l 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.

Blood coagulation Normal hematostasis, fibrinolysis and PC system Blood coagulation K PK Intrinsic pathway

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

Blood coagulation inhibitory systems Cell anticoagulation system Monocyte-macrophage Vascular endothelial cell(VEC) Body fluid anticoagulation

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

Pathogenesis of DIC excessive generation of thrombin defects in inhibitors of coagulation generation of

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

Pathogenesis Excessive generation of thrombin ■ Severe tissue injury Trauma、Obstetrical calamities、Tumours Tissue necrosis TF↑↑

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

1. Severe tissue injury Introduction into the circulation of substances with tissue thromboplastic activity

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

Pathogenesis ■Extensive damage of vascular endothelial cells VEC has the normal anticoagulant effect, damage

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

l 2. Extensive damage of vascular endothelial cells l Infection, shock , hypoxia and

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

l Blood contacts with exposed collagen to trigger intrinsic clotting cascade through activation of

l 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 cause clotting in many animal species and endotoxinemia is a major cause of intravascular clotting.

Pathogenesis Defects in inhibitors of coagulation Antithrombin , protein C, and tissue factor-pathway inhibitor

Pathogenesis Defects in inhibitors of coagulation 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.

Pathogenesis Generation of systemic plasmin and fibrinolytic defect The plasma level of plasminogen-activator inhibitor

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

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

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

Predisposing factors Inappropriately conditioned monocytes-macrophages The reticuloendothelial system can remove most of the products

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. Hypercoagulable state of blood The platelets and several kinds of clotting factors (FⅠ, Ⅱ, Ⅴ, Ⅶ, Ⅸ, Ⅹ, Ⅻ, etc. ) in blood are increased. The activity of anticoagulant materials and or fibrinolysis are decreased.

Predisposing factors Dysfunction of microcirculation Stasis of the microcirculation permits activated clotting factors to

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

Consequences of DIC

Consequences of DIC

Consequences Bleeding

Consequences Bleeding

Consequences Bleeding mechanisms n. Consumption of clotting factors and platelets n. Activation of secondary

Consequences Bleeding mechanisms n. Consumption of clotting factors and platelets n. Activation of secondary fibrinolytic system n. Production of fibrin degradation products

Consequences Disturbance of circulation---Shock ▲ Microthromobus DIC ▲ bleeding Bradykinin, histamine↑ blood returning to

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

Consequences Microangiopathic hemolytic anemia (MHA)

Consequences Microangiopathic hemolytic anemia (MHA)