Disseminated Intravascular Coagulation (DIC) Profile, Comprehensive Plus

Disseminated intravascular coagulation (DIC) is an acquired disorder that typically occurs secondary to an underlying condition.^6-8 DIC can develop secondary to conditions including obstetric accidents (placental abruption, septic abortion), intravascular hemolysis (transfusion reactions), septicemia, viremia, metastatic malignancy, leukemia, burns, severe trauma, acute liver disease, prosthetic devices, and vascular disorders. Low grade DIC can also be observed in cardiovascular, autoimmune, renal vascular, hematologic, and inflammatory disorders. DIC occurs when the normal hemostatic balance is disrupted as the result of a systemic activation of the procoagulant and fibrinolytic systems.⁷ An excessive amount of thrombin is generated as the result of the uncontrolled release of tissue factor (TF) into the circulation. This can occur as the result of damage to the vascular membrane or as a response to agents that stimulate TF release from endothelial cells. Cytokines produced in septic shock or endotoxin from gram-negative bacteria can induce excessive TF release.⁶ TF in turn initiates the extrinsic pathway of coagulation and, through the action of thrombin, the entire coagulation cascade. Thrombin production is normally limited by tissue factor pathway inhibitor, antithrombin, and protein C anticoagulant mechanisms. Under normal circumstances, the mononuclear-phagocyte system removes TF from the circulation while hepatocytes serve to clear activated coagulation proteases and tissue-plasminogen activator from the circulation.⁷ In DIC, hemostatic control by the natural anticoagulant mechanisms is overwhelmed and thrombin production is unchecked.

The clinical manifestations of DIC can be predominantly thrombotic, fibrinolytic with hemorrhage, or both.^6-8 The excessive thrombin generation that occurs in DIC can result in the deposition of fibrin in the microvasculature, leading to thrombosis and tissue ischemia. Overactivation of the coagulation cascade can, in turn, result in bleeding due to the depletion of platelets, fibrinogen, prothrombin, and other hemostatic proteins in what is referred to as a consumption coagulopathy. Increased fibrin production triggers the fibrinolytic system with the conversion of plasminogen to plasmin. Plasmin, in turn, catalyzes the conversion of fibrin to D-dimer and other fibrinogen degradation products. As plasmin levels increase, the levels of its inhibitor, α₂-antiplasmin, become overwhelmed until free plasmin is left to circulate uncontrolled. Free plasmin breaks down both fibrinogen and fibrin-producing degradation products that can interfere with platelet aggregation, further increasing the risk of bleeding.

The symptoms of DIC in certain conditions can be exacerbated by other aspects of the disease. Hepatic dysfunction can lead to diminished production of procoagulant factors and impair the clearance of fibrinogen degradation products, increasing the risk of bleeding.⁶ Abnormal bone marrow function found in leukemia can lead to reduced platelet production and can adversely impact primary hemostasis. D-dimer can be useful in distinguishing DIC from other conditions associated with bleeding, such as vitamin K deficiency and the rare condition, primary fibrinolysis, since these conditions are not associated with excessive thrombin generation.⁶