1. DIC disseminated intravascular coagulation DIC is characterized by widespread coagulation and bleeding in the vascular compartment. DIC begins with massive activation of the coagulation system, resulting in systemic formation of fibrin. The microthrombi that result cause vessel occlusion and tissue ischemia. Multiple organ failure may ensue. Clot formation consumes all available coagulation proteins and platelets, and severe hemorrhage results. concept

2. Coagulation system Coagulation and anti-coagulation Intrinsic pathway Extrinsic pathway Prothrombin ↓ thrombin Fibrinogen →fibrin monomer → polymer → ↓ Anticoagulation system Protein C/thrombomodulin (PC/TM) Antithrombin Ⅲ /heparin (AT Ⅲ ) Tissue factor pathway inhibitor (TFPI) Fibrinolytic system Plasminogen → plasmin Thrombin, Ⅻ a, Ⅺ a, kallikrein ↓ t-PA, u-PA ↑

3. Etiology Infectious disorders Massive trauma Obstetrical complications Malignant tumors Others

4. Pathogenesis Coagulation system activation Severe tissue injury Vascular endothelial cell damage Platelet activation, WBC and RBC destruction Others Decreased anticoagulant Antithrombin Ⅲ, TFPI Fibrinolytic dysfunction Decreased function t-PA↓, PAI-1 ↑ Secondary activation

5. Precipitating factors Monocyte-macrophage system dysfunction Severe hepatic dysfunction Hypercoagulability state Microcirculation dysfunction Fibrinolytic suppression

6. Clinical manifestations Bleeding Shock Organ dysfunction Hemolytic anemia

7. Bleeding Excessive coagulant consumption Secondary plasminogen activation FDP formation Vascular damage

8. Shock Decreased blood flow back to heart due to disseminated microthrombi Decreased blood volume caused by hemorrhage Decreased CO caused by myocardial DIC Vasodilation led by histamine and/or kinins Actions of FDP

9. Organ dysfunction MODS Hemolytic anemia (microangiopathic ) Hemolytic anemia may develop as red cells are damaged as they pass through vessels partially blocked by thrombus. Schistocyte

10. Stage Hypercoagulatory stage PT↓ Consumptive hypocoagulatory stage PT↑, Platlet ↓, fibrinogen ↓ Secondary plasminogen activation stage PT↑, Platlet ↓, fibrinogen ↓ 3P test (+), D-dimer test (+)

11. Prevention and treatment Etiology treatment Improvement of microcirculation Anti-coagulation and anti-fibrinolysis