Disseminated Intravascular Coagulation and BLEEDING IN LIVER FAILURE

Definition

Disseminated intravascular coagulation (DIC), also referred to as consumptive coagulopathy or defibrination, is caused by a wide variety of serious disorders ( Table 161-1 ). In most patients, the underlying process dominates the clinical picture, but in some cases (e.g., occult malignant neoplasm, envenomation), DIC may be the initial or predominant manifestation of the disorder. DIC never occurs in isolation, without an inciting cause.

Pathobiology

DIC is primarily a thrombotic process from a pathophysiologic perspective. However, its clinical manifestation may appear to be widespread hemorrhage in acute cases. The basic pathophysiologic mechanism ( Fig. 161-1 ), regardless of cause, is entry into the circulation of procoagulant substances that trigger systemic activation of the coagulation system and platelets. This results in disseminated deposition of fibrin-platelet thrombi within the microvasculature. In most cases, the procoagulant stimulus is tissue factor, a lipoprotein that is not normally exposed to blood. In DIC, tissue factor gains access to blood by tissue injury, its elaboration by malignant cells, or its expression on the surface of monocytes and endothelial cells by inflammatory mediators. Components of the inflammatory response and the coagulation system are reciprocally activated in some forms of DIC, such as sepsis. Tissue factor triggers generation of the coagulation protease thrombin, which induces fibrin formation and platelet activation. In some specific cases of DIC, procoagulants other than tissue factor (e.g., a cysteine protease or mucin in certain malignant neoplasms) and proteases other than thrombin (e.g., trypsin in pancreatitis, exogenous enzymes in envenomation) provide the procoagulant stimulus.

In acute, uncompensated DIC, coagulation factors are consumed at a rate in excess of the capacity of the liver to synthesize them, and platelets are consumed in excess of the capacity of bone marrow megakaryocytes to release them. The resulting laboratory manifestations under these circumstances are a prolonged prothrombin time (PT), a prolonged activated partial thromboplastin time (aPTT), and thrombocytopenia. Increased fibrin formation in DIC stimulates a heightened process of secondary fibrinolysis, in which plasminogen activators generate plasmin to digest fibrin (and fibrinogen) into fibrin(ogen) degradation products (FDPs). FDPs are potent circulating anticoagulants that further contribute to the bleeding manifestations of DIC. Intravascular fibrin deposition can cause fragmentation of red blood cells and lead to the appearance of schistocytes in blood smears (see Chapter 143 ); however, frank microangiopathic hemolytic anemia is unusual in DIC. Occlusive microvascular thrombosis in DIC can compromise the blood supply to some organs and lead to multiorgan failure, particularly when it is accompanied by systemic hemodynamic, inflammatory, and metabolic derangements.