When procoagulants are produced or introduced into the blood and overcome the anticoagulant mechanisms, intravascular thrombin is generated systemically, which can lead to disseminated intravascular coagulation (DIC). The clinical manifestations of intravascular coagulation include (a) multiorgan dysfunction caused by microthrombi; (b) bleeding caused by consumption of platelets, fibrinogen, and other coagulation factors; and (c) secondary fibrinolysis. Exposure of blood to tissue factor is the most common trigger. This event can occur when mononuclear cells and endothelial cells are induced to generate and express tissue factor during the systemic inflammatory response syndrome (eg, gram-negative and gram-positive infections, fungal septicemia, burns, severe trauma), or when contact is established between blood and tissue factor constitutively present on membranes of cells foreign to blood (eg, malignant, placental, brain, adventitial cells, or traumatized tissues). Laboratory features include thrombocytopenia, reduced levels of fibrinogen and other coagulation factors (leading to prolonged partial thromboplastin, prothrombin, and thrombin times), and elevated levels of D-dimer and fibrin(ogen) degradation products. Several underlying disorders affect these hemostatic parameters and can lead to a false-positive diagnosis of DIC (eg, liver disease–related coagulation abnormalities and thrombocytopenia) or to a false-negative diagnosis (eg, pregnancy-related high fibrinogen levels). Reexamining these variables every 6 to 8 hours may permit a specific diagnosis. Early detection, vigorous treatment of the underlying disorder, and support of vital functions are essential for survival of affected patients. Blood component therapy is effective in patients who bleed excessively, whereas heparin administration is indicated in a limited number of circumstances, such as overt macrovascular thrombosis. Intravascular coagulation and its underlying disorders contribute to a high rate of mortality. The severity of the organ dysfunction and extent of hemostatic failure, as well as increasing patient age, have been associated with a grave prognosis.
Disseminated intravascular coagulation (DIC) is a clinicopathologic syndrome in which widespread intravascular coagulation occurs as a result of exposure to or production of procoagulants insufficiently balanced by natural anticoagulant mechanisms and endogenous fibrinolysis. Perturbation of the endothelium in the microcirculation, along with stimulated inflammatory cells and release of inflammatory mediators, plays a key role in this mechanism. DIC may cause tissue ischemia from occlusive microthrombi, bleeding from the consumption of platelets and coagulation factors, and, in some cases, an excessive fibrinolytic response. DIC complicates a variety of disorders, and the complexity of its pathophysiology has made it the subject of voluminous literature.1–7
In 1834, Dupuy reported that injection of brain material into animals caused widespread clots in blood vessels, thus providing the first description of DIC.8 In 1865, Trousseau described the tendency toward thrombosis, sometimes disseminated, in cachectic patients with malignancies.9 In 1873, Naunyn showed that disseminated thrombosis could be evoked by IV injection of dissolved red cells, and Wooldridge demonstrated that the procoagulant involved was a substance contained in the stroma of the red cells.10–12
In 1955, Ratnoff and associates ...