【【 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
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
ConsequencesConsequences
Microangiopathic hemolytic anemia (MHA)Microangiopathic hemolytic anemia (MHA)