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