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Etiologies And Mechanism Of


Intravascular Coagulation)
Disseminated intravascular

Disseminated - wide spread

Intravascular - inside the
Definition :
This is a acute,
sub acute,
chronic thrombo haemorrhagic
disorder. Characterized by excessive
activation of coagulation and
formation of thrombosis in the
microvasculature of our body.
DIC is not a kind of independent disease, but
it is a middle process or complication of some

Its is an imbalance between the coagulation

process and anticoagulation process. It is a
syndrome characterized by massive
And consumption of coagulation proteins
fibrinolytic proteins and platelets.

DIC is not a primary disease, but a

disorder secondary to numerous
triggering events happened due to
some other serious diseases.
These are the some causes of DIC

infectious diseases
Obstetric complications
Severe tissue injury
Vascular and cardiac disorders
Some other diseases
DIC is often a consequence of severe
infection. In DIC caused by gram ve bacteria
the extrinsic pathway of haemostasis is
activated by the release of tissue factor.
This leads to clot generation
Then fibrinolytic mechanism starts which
further impairs the haemostasis and initiate
Eg:- infectious diseases(viral,bacterial,mycotic,
DIC is often associated with
malignancy, eg acute promyelocytic
leukaemia treatment that triggers TF
like agent release or causes the
intravascular coagulation.
IL-1 and tumour necrosis factor
induces expression of TF.
Eg:-malignant diseases
In extensive tissue injuries,
Tissue factor is constitutively present in cell
membranes of most tissues including the Ecs of
blood vessels.
DIC associated with massive trauma, malignancy,
Abruptio placentae, intrauterine fetal death,
Amniotic fluid embolism and other disorders trigger
procoagulants release and activate coagulation
Damage of vascular endothelial cells:
Ecs can be damaged and altered by
trauma, hypoxia, acidosis, sepsis,
endotoxin and others the changed Ecs
have properties of activated
Conversion of normal anti-coagulant
phenotype to pro coagulant
Expression of adhesion molecules,
Pro coagulants entering circulation:
Under normal circumstances blood is
not exposed to TF but when blood
becomes exposed to tissues or cells,
foreign to blood entering the blood
stream factor 10 is activated and the
coagulation system ignited this leads
to DIC. Eg:-amniotic fluid
embolism,truma,burns or tumour cells.
Snake bites and other venomous bites
can cause DIC these may lead to
death. The active compounds in snake
venom affecting coagulation my
promote the activation of factor 10
and activation of prothrombin in the
presence of calcium ions.
Antigen-antibody complexes may
initiate factor 12 to 12a or damage
platelets thereby activating the
coagulation system leads to DIC.
Factors influencing the formation and
development of DIC
Inappropriately conditioned
Impairment of liver and spleen
Hypercoagulable status
Dysfunction of microcirculation
Mechanisms Of DIC
Under homeostatic
conditions, the body is
maintained in a finely
tuned balance of
Coagulation and
Mechanism Of DIC
The activation of coagulation
cascade yields Thrombin
that converts Fibrinogen into
Fibrin; the stable fibrin clot
being the final product of
Mechanism Of DIC
Activation of Fibrinolytic
system generates Plasmin (in
the presence of thrombin)
which is responsible for the
lysis of fibrin clots.Breakdown
of fibrin and fibrinogen results
in FSPs or FDPs.
Mechanism Of DIC
In a state of homeostasis,
the presence of Plasmin is
critical, as it is central
proteolytic enzyme of
coagulation and is also
necessary for breakdown of
Mechanism Of DIC
In DIC (Disseminated
Intravascular Coagulation) , the
processes of Coagulation and
Fibrinolysis are dysregulated.
One critical mediator of DIC is the
release of trans membrane
glycoprotein called Tissue
Mechanism Of DIC
Coagulation Pathway:
TF is present on surface of
many cells including
Monocytes, Endothelial cells
and Macrophages.
In normal conditions TF is not
in contact with general blood
Mechanism Of DIC
TF is exposed to circulation
during vascular damage.
Ex: TF is released in response to
exposure to Cytokines and TNF.
TF is also abundant in the
tissues of Brain, Lungs and
Mechanism Of DIC
I. Damage Of Vascular Endothelial
.In normal endogenous anti
coagulation pathways, the
activation of coagulation cascade is
down regulated by anti- thrombin III
inhibiting Xa and thrombin.
Mechanism Of DIC
In endogenous pathway of DIC,
the level of tissue plasminogen
activator (tPA) is down regulated
and the activation of TPA-1 is up
tPA can induce Plasmin formation
which degrades formed fibrin
clots to fibrin peptides.
Mechanism Of DIC
In patients with severe
infections, the effects of LPS
and secondary induced
effector molecules are
LPS initiates the Cytokine
Mechanism Of DIC
Secondary effectors that
become important include
Nitric Oxide (NO), PGI2
(Prosta Cyclin),ADP.
All these secondary effectors
are produced by activated
Endothelial Cells.
Mechanism Of DIC
II. Destruction Of Blood cells and
activation of Platelets:
.In DIC, caused by bacterial
sepsis, the extrinsic pathway is
activated by endotoxin, IL-1, and
TNF which induce expressions of
TF on circulating monocytes &
Mechanism Of DIC
This induced expression of
TFs on circulating
Monocytes and PMNs
leads to Thrombin
generation and fibrin
Mechanism Of DIC
III.Destruction or Activation of
.When a blood vessel is
injured then the platelets
adhere to exposed ECM via
vWF ( von Willebrand Factor).
Mechanism Of DIC
These platelets are activated
and release ADP and TXA2.
TXA2 (Thromboxane A2)
leads to further aggregation
of platelets and formation of
Primary Haemostatic Plug or
Primary Platelet Plug.
Mechanism Of DIC
The activation of
coagulation cascade
involving TFs and platelet
phospholipids results in
fibrin polymerization and
eventually forming a fibrin
Mechanism Of DIC
Anti- Coagulant Pathway:
I. Tissue Factor Pathway
.The extrinsic pathway is
rapidly inhibited by TFPI.
.It inhibits the activation of
Factor X.
Mechanism Of DIC
II. Protein C :
.This is a major physiological
anti- coagulant.
.Protein C is activated in the
presence of ThromboModulin
by Thrombin.
Mechanism Of DIC
III.Anti-Thrombin III:
.It is attached to Heparin
Sulphate that is present on
Endothelial Cells.
.It inhibits the activated
factors of Xa, IXa, XIa & XIIa.
Mechanism Of DIC
IV.Prosta Cyclin (PGI2):
.It is released by
.It inhibits platelets
activation by decreasing
the level of calcium.
Mechanism Of DIC
The causes Of DIC are generally
The mechanisms that trigger,
generate & develop DIC act on
processes that are involved in
the ways of platelet adhesion
and aggregation as well as the
activation of Intrinsic & Extrinsic