Transcript Consequences

Disseminated Intravascular
Coagulation
(DIC)
Concept
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
status
thrombotic state
Prothrombotic
state
Pathological features
Bleeding、Shock、MODF、Microangiopathic hemolytic anemia
Cause
Condition associated with DIC
1. Basic disease





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
Ⅻa
Extrinsic pathway
collagen
HK
Ⅹa
Ⅻ
Ⅻa
TF
Ⅺ
Ⅺa
Ⅶa
Ⅶ
Ca2+
Ca2+
Ⅸa
Ⅸ
Ⅸ
Ⅷa
Ⅷ
PL+Ca2+
TFPI
Ⅹa
Ⅹ
Ⅹ
Ⅴ
ⅩⅢ
Ⅴa
2+
Ⅹa、Ⅱa
PL+Ca2+ Ca
F1+2
ⅩⅢa
（-）
Ⅱa
Ⅱ
Ca2+
AT
FPA/FPB
Fbg
FM
Fbn
Blood coagulation
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
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↑↑
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 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.
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

2. Extensive damage of vascular
endothelial cells
 Infection, shock , hypoxia and immune
reactions can damage the vascular
endothelial cells.

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.
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 thpe 1 is
increased, which inhibits the fibrinolytic system.
Predisposing factors
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 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 accumulate in blood capillary making it easier to
develop into DIC.
Severe hepatic dysfunction
Consequences
Consequences of DIC
Consequences
Bleeding
Consequences
Bleeding mechanisms
Consumption of clotting factors and platelets
Activation of secondary fibrinolytic system
Production of fibrin degradation products
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↓
肾小
球
肺
脏
Consequences
Microangiopathic hemolytic anemia (MHA)