Disseminated Intravascular Coagulation
Coagulation cascade
Extrinsic system (tissue damage)
Intrinsic system (surface contact)
XII
XIIa
Tissue factor
XIa
XI
IX
VIIa
IXa
VIII
VIIIa
X
Vitamin K dependant factors
VII
Xa
V
Va
II
Fibrinogen
IIa
IIa
(Thrombin)
Fibrin
DIC may be initiated by
Exposure of blood to tissue factor (eg after trauma).
Endothelial cell damage (eg by endotoxin or cytokines).
Release of proteolytic enzymes into the blood .
( eg pancreas , snake venom )
Infusion or release of activated clotting factor.
(eg Factor IX concentrate )
Massive thrombosis.
Severe hypoxia and acidosis.
Disseminated Intravascular Coagulation
(DIC) Mechanism
Systemic activation
of coagulation
Intravascular
deposition of fibrin
Thrombosis of small
and midsize vessels
with organ failure
Depletion of platelets
and coagulation factors
Bleeding
Acute DIC
Acute DIC develops when blood is exposed to large
amounts of tissue factor over a brief period of time .
- Bleeding
- Acute renal failure
- Hepatic dysfunction
- Pulmonary disease
- Central nervous system dysfunction
- Malignancy
Chronic DIC:
chronic DIC develops when blood is
continuously or intermittently exposed
to small amounts of tissue factor and
compensatory mechanisms in the liver
and BM are largely able to replenish
the depleted coagulation proteins and
platelets .
Chronic DIC:
*Malignancy,
the most
particularly solid tumors, ( is
common cause of chronic DIC).
*Venous thromboses
commonly present as
deep venous thrombosis in the extremities
or superficial migratory thrombophlebitis
(Trousseau's syndrome),
*Arterial thromboses can produce digital
ischemia, renal infarction, or stroke.
DIAGNOSIS of DIC
Acute DIC:
Fibrin degradation product or D-dimer levels.
Prothrombin time.
Activated partial thromboplastin time.
deficiencies of factors XII, XI, IX and VIII.
Plasma fibrinogen concentration .
Chronic DIC:
platelet count moderately reduced.
plasma fibrinogen is often normal or slightly elevated.
PT and PTT may be within normal limits.
DIC versus fibrinolysis:
Primary fibrinogenolysis occurs when plasmin is
generated in the absence of thrombosis. It is may
occur in certain conditions, such as :
direct infusion of thrombolytic agents and in
patients with prostate cancer .
It can be distinguished from DIC by the absence of
elevated level of D-dimers.
However, when fibrinolysis is prominent, elevated
levels of D-dimer and other fibrin degradation
products will be present.
DIC versus TTP-HUS:
The pathogenesis of DIC, a thrombotic
microangiopathy resulting from activation of the
coagulation system, is different from the
pathogenesis of another thrombotic
microangiopathy,
Thrombotic thrombocytopenic purpura-hemolytic
uremic syndrome ( TTP-HUS ) ,
which results from primary platelet activation
due in many cases to a congenital or acquired
defect in von Willebrand factor cleaving protease or
primary endothelial injury.
TREATMENT 0f DIC
Platelet transfusion
Fresh frozen plasma
Heparin ?
Protein C concentrate
Treatment of the underlying disease
Definition of DIC
• DIC is a clinicopathologic syndrome in which
widespread intravascular coagulation is
induced by procoagulant that are introduce or
produce in circulation and overcome the natural
anticoagulant mechanisms.
• DIC may cause tissue ischemia from occlusive
microthrombi as well as bleeding from both
consumption of platlet and coagulation factor
and anticoagulation effect of product of
secondary fibrinolysis.
Common clinical conditions associated with
Disseminated Intravascular Coagulation
Activation of both coagulation and fibrinolysis
Triggered by
• Sepsis
• Trauma
– Head injury
– Fat embolism
• Malignancy
• Obstetrical
complications
– Amniotic fluid embolism
– Abruptio placentae
• Vascular disorders
• Reaction to toxin (e.g.
snake venom)
• Immunologic disorders
– Severe allergic reaction
– Transplant rejection
Pathogenesis of DIC
Release of
thromboplastic
material into
circulation
Coagulation
Fibrinogen
Thrombin
Fibrin
Monomers
Fibrin Clot
(intravascular)
Consumption of
coagulation factors;
 a PTT
 PT
 TT
Fibrinolysis
 Fibrinogen
Presence of
Plasmin
plasmin
 FDP
Intravascular clot
Fibrin(ogen)
 Platelets
Degradation
Schistocytes
Products
Plasmin
Disseminated Intravascular Coagulation
Treatment approaches
• Treatment of underlying disorder
• Platelet transfusion
• Fresh frozen plasma
• Anticoagulation with heparin
• Coagulation inhibitor concentrate (ATIII)
Management of underlying disordes
although the pt may benefit from other treatment survival
depend on vigorous treatment of underlying disorder :
•
•
•
•
•
Intensive antibiotic treatment in G- bacteremia
Hysterectomy in abruptio placenta
Resection of aortic aneurism
Debridment of crush tissue
Volume replacement , correction of hypotention &
oxygenation, restore the function of coagulation
inhibitory system.
Replacement therapy
• For thrombocytopenia : 6-10 U plat (ideally rise
to more than 50000-100000)
• For hypofibrinogenemia (<100 ) : 8-10 U
Cryopercipitate
• For coagulation factor depletion : 1-2 U FFP
• ( depend on severity of depletion & body weight)
Classification of thrombocytopenia
• Associated with
thrombosis
– Thrombotic
thrombocytopenic
purpura
– Heparin-associated
thrombocytopenia
– Trousseau’s syndrome
– DIC
– AML (m3)
• Associated with
bleeding
– Immune-mediated
thrombocytopenia
(ITP)
– Most others
Classification of platelet disorders
• Quantitative
disorders
– Abnormal distribution
– Dilution effect
– Decreased
production
– Increased
destruction
• Qualitative disorders
– Inherited disorders
(rare)
– Acquired disorders
• Medications
• Chronic renal failure
• Cardiopulmonary
bypass