Disseminated Intravascular Disseminated Intravascular CoagulationCoagulation

(DIC)(DIC)

【【 Change of basic pathology Change of basic pathology 】】 Key changeKey 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 It is characterized by the activation of the coagulation system with resultant consumption of a variety of coagulation proteins and platelets, which resultant consumption of a variety of coagulation proteins and platelets, which results in hemorrhagic diathesis and ischemic injury to various tissuesresults in hemorrhagic diathesis and ischemic injury to various tissues. .

ConceptConcept

ConceptConcept

Proth

romb

otic staP

rothrom

botic sta

tete throm

botic state

throm

botic state

Low

L

ow

consu

mp

tion of

consu

mp

tion of

coagulation

coagu

lation

status

status

Secon

dary fib

riS

econd

ary fibri

nolysis

nolysis

Basic pathological processBasic pathological process

ConceptConcept

Hypercoagulable stateHypercoagulable state Hypocoagulable stateHypocoagulable state

Pathological featuresPathological features

Bleeding 、 Shock 、 MODF 、 Microangiopathic hemolytic anem

ia

1. 1. Basic diseaseBasic disease

Condition associated with DICCondition associated with DIC

CauseCause

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 res

ult in local activation of coagulation; Obstetric accidents---includes amniotic fluidemboli

sm and placental abruption, the fetus, the placenta, and the amniotic fluid are rich in thromboplastic substances.

Normal hematostasis, fibrinolysis and PC system

K PK aⅫ collagen HK a Ⅹ

Ⅻ Ⅻa TF Ⅺ Ⅺa a Ⅶ Ⅶ Ca2+ Ca2+ Ⅸ Ⅸ Ⅷ Ⅹ Ⅹ Ⅴ ⅩⅢ Ca2+ aⅩ 、Ⅱ a F1+2 a ⅩⅢ Ⅱa CaⅡ 2+

FPA/FPB Fbg FM Fbn

Intrinsic pathwayIntrinsic pathway Extrinsic pathwayExtrinsic pathway

Ⅹa

Ⅴa

PL+Ca2+

Ⅸa

Ⅷa

PL+Ca2+

Blood coagulationBlood coagulation

ATAT

TFPITFPI

（（ --））

Blood coagulationBlood coagulation

Monocyte-macrophage

Vascular endothelial cell （ VEC ）

Anticoagulation factors in plasma AT 、 TFPI

Protein C system

Fibrinolytic system

coagulation inhibitory coagulation inhibitory systemssystems

Cell anticoagulation system

Body fluid anticoagulation system

Blood coagulationBlood coagulation

excessive generation of thrombinexcessive generation of thrombin

defects in inhibitors of coagulationdefects in inhibitors of coagulation

generation of systemic plasmin and fibrinolytic defegeneration of systemic plasmin and fibrinolytic defectct

Pathogenesis of DICPathogenesis of DIC

PathogenesisPathogenesis

TraumaTrauma 、、 Obstetrical calamitiesObstetrical calamities 、、 TumoursTumours

Tissue necrosis TF↑↑ Tissue necrosis TF↑↑

Ⅱ Ⅱ a ↑↑abnormal activation of the extrinsic coagulation systema ↑↑abnormal activation of the extrinsic coagulation system

■■ Severe tissue injurySevere tissue injury

Fbg Fbn + active platelet Fbg Fbn + active platelet

Microthromobus↑↑↑ DIC Microthromobus↑↑↑ DIC

PathogenesisPathogenesis

Excessive generation of thrombinExcessive generation of thrombin

1. Severe tissue injury1. Severe tissue injury

Introduction into the circulation of substances witIntroduction into the circulation of substances with tissue thromboplastic activity may initiate the exh tissue thromboplastic activity may initiate the extrinsic clotting reactions. trinsic clotting reactions.

This can occur with This can occur with severe trauma, wounds, major severe trauma, wounds, major operation, malignant necrosisoperation, malignant necrosis and by the actions o and by the actions of uterine contents in patients with obstetrical compf uterine contents in patients with obstetrical complications.lications.

M M 、 、 PMN activatedPMN activated

cytokines, completment, ROS↑cytokines, completment, ROS↑

■■Extensive damage of vascular endothelial cellsExtensive damage of vascular endothelial cells

VEC has the normal anticoagulant effect, damage VEC has a procoagulVEC has the normal anticoagulant effect, damage VEC has a procoagul

ant effect.ant effect.

infection, infection, ETET, hypoxia, acidosis, hypoxia, acidosis

VEC injuryVEC injury

TF↑ collagen fibers exposedTF↑ collagen fibers exposed

micro-thrombosis micro-thrombosis aⅫaⅫ ↑platelet adhesion and aggregation ↑platelet adhesion and aggregation

DIC coagulation increasedDIC coagulation increased

PathogenesisPathogenesis

Direct way Direct way

Indirect wayIndirect way

2. Extensive damage of vascular 2. Extensive damage of vascular endothelial cells endothelial cells

Infection, shockInfection, shock , , hypoxiahypoxia and and immuneimmune reactions reactions can damage the vascular can damage the vascular endothelial cells.endothelial cells.

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

Defects in inhibitors of coagulationDefects in inhibitors of coagulation

PathogenesisPathogenesis

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

Generation of systemic plasmin and fibrinolytiGeneration of systemic plasmin and fibrinolytic defectc defect

PathogenesisPathogenesis

The plasma level of plasminogen-activator inhibitor thpe 1 is The plasma level of plasminogen-activator inhibitor thpe 1 is increased, which inhibits the fibrinolytic system.increased, which inhibits the fibrinolytic system.

Predisposing factors to DICPredisposing factors to DIC

Inappropriately conditioned monocytes-macrophagesInappropriately conditioned monocytes-macrophages

Liver injuryLiver injury

Hypercoagulable state Hypercoagulable state

Dysfunction of microcirculation Dysfunction of microcirculation

Predisposing factorsPredisposing factors

Hypercoagulable state of bloodHypercoagulable state of blood

Predisposing factorsPredisposing factors

Inappropriately conditioned monocytes-macrophagesInappropriately conditioned monocytes-macrophages

The The reticuloendothelial systemreticuloendothelial system can remove most of th can remove most of the products of introvascular coagulation and various inie products of introvascular coagulation and various initiators of the process from the circulation. tiators of the process from the circulation.

The platelets and several kinds of clotting factors (F ,ⅠThe platelets and several kinds of clotting factors (F ,Ⅰ, , , , , , ⅡⅤ Ⅶ Ⅸ Ⅹ Ⅻ, , , , , , ⅡⅤ Ⅶ Ⅸ Ⅹ Ⅻ etcetc.) in blood are .) in blood are increasedincreased. .

The activity of anticoagulant materials and or fibrinolyThe activity of anticoagulant materials and or fibrinolysis are sis are decreaseddecreased. .

StasisStasis of the microcirculation permits activated clotting of the microcirculation permits activated clotting factors to accumulate in blood capillary making it easier to factors to accumulate in blood capillary making it easier to develop into DIC. develop into DIC.

Dysfunction of microcirculationDysfunction of microcirculation

Predisposing factorsPredisposing factors

Severe hepatic dysfunctionSevere hepatic dysfunction

Consequences of DICConsequences of DIC

ConsequencesConsequences

ConsequencesConsequences

BleedingBleeding

CConsumption of clotting factors and plateletsonsumption of clotting factors and platelets

Activation of secondary fibrinolytic systemActivation of secondary fibrinolytic system

Production of fibrin degradation productsProduction of fibrin degradation products

Bleeding mechanismsBleeding mechanisms

ConsequencesConsequences

▲ ▲ Microthromobus blood returning to heart ↓ Microthromobus blood returning to heart ↓

DIC bleeding blood volume↓DIC bleeding blood volume↓

▲▲ Bradykinin,histamineBradykinin,histamine↑↑ vasodilation vasodilation blood pressure↓blood pressure↓

FDP can increased to dilates vessels that cause hypotensionFDP can increased to dilates vessels that cause hypotension

▲▲ Heart functionHeart function↓↓↓↓

cardiac output↓cardiac output↓

blood pressure↓blood pressure↓

Disturbance of circulation---ShockDisturbance of circulation---Shock

ConsequencesConsequences

肾小肾小球球

肺肺脏脏

ConsequencesConsequences

Microangiopathic hemolytic anemia (MHA)Microangiopathic hemolytic anemia (MHA)