DIC occurs as a complication of a wide variety of disorders; it is caused by the systemic activation of coagulation and results in the formation of thrombi throughout the microcirculation. As a consequence, platelets and coagulation factors are consumed and, secondarily, fibrinolysis is activated. Thus, DIC can give rise either to tissue hypoxia and microinfarcts caused by myriad microthrombi or to a bleeding disorder related to pathologic activation of fibrinolysis and the depletion of the elements required for hemostasis (hence the term consumptive coagulopathy). This entity probably causes bleeding more commonly than all of the congenital coagulation disorders combined.
Before discussing specific disorders associated with DIC, we must first consider in a general way the pathogenic mechanisms by which intravascular clotting occurs. Reference to earlier comments on normal blood coagulation (Chapter 4) may be helpful at this point. It suffices to recall that clotting can be initiated by either the extrinsic pathway, which is triggered by the release of tissue factor (tissue thromboplastin); or the intrinsic pathway, which involves the activation of factor XII by surface contact, collagen, or other negatively charged substances. Both pathways lead to the generation of thrombin. Clotting normally is limited by the rapid clearance of activated clotting factors by the macrophages and the liver, endogenous anticoagulants (e.g., protein C), and the concomitant activation of fibrinolysis.
DIC usually is triggered by either (1) the release of tissue factor or thromboplastic substances into the circulation or (2) widespread endothelial cell damage (
Fig.
12.30 ). Thromboplastic substances can be released into the circulation from a variety of sources—for example, the placenta in obstetric complications or certain types of cancer cells, particularly those of acute promyelocytic leukemia and adenocarcinomas. Cancer cells may also provoke coagulation in other ways, such as by releasing proteolytic enzymes and by expressing tissue factor. In gram-negative and gram-positive sepsis (important causes of DIC), endotoxins or exotoxins stimulate the release of tissue factor from monocytes. Activated monocytes also release IL-1 and tumor necrosis factor, both of which stimulate the expression of tissue factor on endothelial cells and simultaneously decrease the expression of thrombomodulin. The latter, as discussed, activates protein C, an anticoagulant (Chapter 4). The net result of these alterations is the enhanced generation of thrombin and the blunting of inhibitory pathways that limit coagulation.
Severe endothelial cell injury can initiate DIC by causing the release of tissue factor and by exposing subendothelial collagen and vWF. However, even subtle forms of endothelial damage can unleash procoagulant activity by stimulating tissue factor expression on endothelial cell surfaces. Widespread endothelial injury can be produced by the deposition of antigen-antibody complexes (e.g., in systemic lupus erythematosus), by temperature extremes (e.g., after heat stroke or burn injury), or by infections (e.g., resulting from meningococci or rickettsiae). As discussed in Chapter 4, endothelial injury is an important consequence of systemic inflammatory response syndrome (SIRS) triggered by sepsis and other systemic insults, and, not surprisingly, DIC is a frequent complication of SIRS.
Disorders associated with DIC are listed in