IN THE NAME OF GOD

Disseminated Intravascular Coagulation Dr.h-kayalhaAnesthesiologist

DIC n An acquired syndrome characterized by systemic intravascular coagulation n Coagulation is always the initial event. n Most morbidity and mortality depends on extent of intravascular thrombosis n Multiple causes WWW. Coumadin.com

Hemostatic Balance ATIII Clotting Factors Tissue factor * PAI-1 Antiplasmin TFPI Prot. C Prot. S Procoagulant Anticoagulant Fibrinolytic System

DIC n An acquired syndrome characterized by systemic intravascular coagulation n Coagulation is always the initial event SYSTEMIC ACTIVATION OF COAGULATION Intravascular deposition of fibrin Depletion of platelets and coagulation factors Thrombosis of small and midsize vessels Bleeding Organ failure DEATH

Pathophysiology of DIC n Activation of Blood Coagulation n Suppression of Physiologic Anticoagulant Pathways n Impaired Fibrinolysis n Cytokines

Pathophysiology of DIC n Activation of Blood Coagulation u Tissue factor/factor VIIa mediated thrombin generation via the extrinsic pathway F complex activates factor IX and X u TF F endothelial cells F monocytes F Extravascular: lunglung kidneykidney epithelial cellsepithelial cells

Pathophysiology of DIC n Suppression of Physiologic Anticoagulant Pathways u reduced antithrombin III levels u reduced activity of the protein C-protein S system u Insufficient regulation of tissue factor activity by tissue factor pathway inhibitor (TFPI)

Pathophysiology of DIC n Impaired Fibrinolysis u relatively suppressed at time of maximal activation of coagulation due to increased plasminogen activator inhibitor type 1

Pathophysiology of DIC - Cytokines n Cytokines u IL-6, and IL-1 mediates coagulation activation in DIC u TNF-  F mediates dysregulation of physiologic anticoagulant pathways and fibrinolysis F modulates IL-6 activity u IL-10 may modulate the activation of coagulation Coagulation Inflamation

Diagnosis of DIC 4 Presence of disease associated with DIC 4 Appropriate clinical setting u Clinical evidence of thrombosis, hemorrhage or both. : Laboratory studies u no single test is accurate u serial test are more helpful than single test

Conditions Associated With DIC n Malignancy u Leukemia u Metastatic disease n Cardiovascular u Post cardiac arrest u Acute MI u Prosthetic devices n Hypothermia/Hyperthermia n Pulmonary u ARDS/RDS u Pulmonary embolism n Severe acidosis n Severe anoxia n Collagen vascular disease n Anaphylaxis

Conditions Associated With DIC n Infectious/Septicemia u Bacterial F Gm - / Gm + u Viral F CMV F Varicella F Hepatitis u Fungal n Intravascular hemolysis n Acute Liver Disease n Tissue Injury u trauma u extensive surgery u tissue necrosis u head trauma n Obstetric u Amniotic fluid emboli u Placental abruption u Eclampsia u Missed abortion

Clinical Manifestations of DIC Ischemic Findings are earliest! Bleeding is the most obvious clinical finding

Clinical Manifestations of DIC

Microscopic findings in DIC n Fragments n Schistocytes n Paucity of platelets

Laboratory Tests Used in DIC n D-dimer* n Antithrombin III* n Fibrinopeptide A* n Platelet factor 4* n Fibrin Degradation Prod n Platelet count n Protamine test n Thrombin time n Fibrinogen n Prothrombin time n Activated PTT n Protamine test n Coagulation factor levels *Most reliable test

Laboratory diagnosis n Thrombocytopenia u plat count <100,000 or rapidly declining n Prolonged clotting times (PT, APTT) n Presence of Fibrin degradation products or positive D-dimer n Low levels of coagulation inhibitors u AT III, protein C n Low levels of coagulation factors u Factors V,VIII,X,XIII n Fibrinogen levels not useful diagnostically

Differential Diagnosis n Severe liver failure n Vitamin K deficiency n Liver disease n Thrombotic thrombocytopenic purpura n Congenital abnormalities of fibrinogen n HELLP syndrome

Treatment of DIC n Stop the triggering process. u The only proven treatment! n Supportive therapy n No specific treatments u Plasma and platelet substitution therapy u Anticoagulants u Physiologic coagulation inhibitors

Plasma therapy n Indications u Active bleeding u Patient requiring invasive procedures u Patient at high risk for bleeding complications n Prophylactic therapy has no proven benefit. n Fresh frozen plasma(FFP): u provides clotting factors, fibrinogen, inhibitors, and platelets in balanced amounts. u Usual dose is ml/kg

Platelet therapy n Indications u Active bleeding u Patient requiring invasive procedures u Patient at high risk for bleeding complications n Platelets u approximate dose 1 unit/10kg

Blood n Replaced as needed to maintain adequate oxygen delivery. u Blood loss due to bleeding u RBC destruction (hemolysis)

Coagulation Inhibitor Therapy n Antithrombin III n Protein C concentrate n Tissue Factor Pathway Inhibitor (TFPI) n Heparin

n The major inhibitor of the coagulation cascade u Levels are decreased in DIC. u Anticoagulant and antiinflammatory properties n Therapeutic goal is to achieve supranormal levels of ATIII (> %). u Experimental data indicated a beneficial effect in preventing or attenuating DIC in septic shock F reduced DIC scores, DIC duration, and some improvement in organ function u Clinical trials have shown laboratory evidence of attenuation of DIC and trends toward improved outcomes. u A clear benefit has not been established in clinical trials. Antithrombin III

Protein C Concentrates n Inhibits Factor Va, VIIa and PAI-1 in conjunction with thrombomodulin. n Protein S is a cofactor n Therapeutic use in DIC is experimental and is based on studies that show: u Patients with congenital deficiency are prone to thromboembolic disease. u Protein C levels are low in DIC due to sepsis. u Levels correlate with outcome. u Clinical trials show significantly decreased morbidity and mortality in DIC due to sepsis.

Tissue Factor Pathway Inhibitor n Tissue factor is expressed on endothelial cells and macrophages n TFPI complexes with TF, Factor VIIa,and Factor Xa to inhibit generation of thrombin from prothrombin n TF inhibition may also have antiinflammatory effects n Clinical studies using recombinant TFPI are promising.

Heparin n Use is very controversial. Data is mixed. n May be indicated in patients with clinical evidence of fibrin deposition or significant thrombosis. n Generally contraindicated in patients with significant bleeding and CNS insults. n Dosing and route of administration varies. n Requires normal levels of ATIII.

Antifibrinolytic Therapy n Rarely indicated in DIC u Fibrinolysis is needed to clear thrombi from the micro circulation. u Use can lead to fatal disseminated thrombosis. n May be indicated for life threatening bleeding under the following conditions: u bleeding has not responded to other therapies and: u laboratory evidence of overwhelming fibrinolysis. u evidence that the intravascular coagulation has ceased. n Agents: tranexamic acid, EACA

Summary n DIC is a syndrome characterized systemic intravascular coagulation. n Coagulation is the initial event and the extent of intravascular thrombosis has the greatest impact on morbidity and mortality. n Important link between inflammation and coagulation. n Morbidity and mortality remain high. n The only proven treatment is reversal or control of the underlying cause.

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