Disseminated Intravascular Disseminated Intravascular Coagulation Coagulation
Jan 06, 2016
Disseminated Intravascular CoagulationDisseminated Intravascular Coagulation
XIIaXIIa
Coagulation cascadeCoagulation cascade
IIa
Intrinsic system (surface contactIntrinsic system (surface contact))
XIIXII
XIXI XIa
Tissue factorTissue factor
IXIX IXa VIIa VIIVII
VIIIVIII VIIIaVIIIa
Extrinsic system Extrinsic system (tissue damage(tissue damage))
XX
VV VaVaIIII
FibrinogenFibrinogen FibrinFibrin
(Thrombin(Thrombin))IIa
Vitamin K dependant factorsVitamin K dependant factors
Xa
DIC may be initiated byDIC 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 Disseminated Intravascular Coagulation (DIC) Mechanism(DIC) Mechanism
Systemic activationof coagulation
Intravasculardeposition of fibrin Depletion of platelets
and coagulation factors
Bleeding
Thrombosis of smalland midsize vessels
with organ failure
Acute DIC 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, particularly solid tumors, ( is
the most 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 DICDIAGNOSIS of DICAcute DIC:
Fibrin degradation product or D-dimer levels.
Prothrombin time.
Activated partial thromboplastin time.
Plasma fibrinogen concentration .
deficiencies of factors XII, XI, IX and VIII.
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: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 DICTREATMENT 0f DIC
Platelet transfusion Fresh frozen plasma
Heparin ?
Protein C concentrate
Treatment of the underlying disease
Definition of DICDefinition 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 withCommon clinical conditions associated withDisseminated Intravascular CoagulationDisseminated Intravascular Coagulation
• 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
Activation of both coagulation and fibrinolysis Triggered by
Pathogenesis of DICPathogenesis of DIC
Coagulation Fibrinolysis
Fibrinogen
FibrinMonomers
Fibrin Clot(intravascular)
Fibrin(ogen)Degradation
Products
Plasmin
Thrombin Plasmin
Release of thromboplastic
material intocirculation
Consumption ofcoagulation factors;
a PTT PT TT
FibrinogenPresence of
plasmin FDP
Intravascular clot Platelets
Schistocytes
Disseminated Intravascular CoagulationDisseminated Intravascular CoagulationTreatment approachesTreatment approaches
• Treatment of underlying disorder
• Platelet transfusion
• Fresh frozen plasma• Anticoagulation with heparin
• Coagulation inhibitor concentrate (ATIII)
Management of underlying disordesManagement 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 therapyReplacement 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 thrombocytopeniaClassification of thrombocytopenia
• Associated with bleeding– Immune-mediated
thrombocytopenia (ITP)
– Most others
• Associated with thrombosis– Thrombotic
thrombocytopenic purpura
– Heparin-associated thrombocytopenia
– Trousseau’s syndrome
– DIC
– AML (m3)
Classification of platelet disordersClassification 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