Consumptive coagulopathy, better known as disseminated intravascular coagulation (DIC), is characterized by abnormally increased activation of procoagulant pathways. This results in intravascular fibrin deposition, and decreased levels of hemostatic components, including platelets, fibrinogen, and other clotting factors. Although chronic DIC can be asymptomatic, acute DIC results in bleeding and intravascular thrombus formation that can lead to tissue hypoxia, multiorgan dysfunction, and death. 
The excess production of thrombin is central to the process of DIC. In addition to the conversion of fibrinogen to fibrin, thrombin has numerous other effects relative to the coagulation cascade. Thrombin contributes to the activation of factors V, VIII, and XIII (fibrin-stabilizing factor) and has an activating effect on platelets. Modulation of anticoagulant molecules also occurs by means of a thrombin-dependent mechanism. This mechanism includes generation of activated protein C and protein S and the activation of tissue-type plasminogen activator (tPA) with subsequent inhibition of activated factors V and VIII, plasminogen activator inhibitor-1 (PAI-1), and thrombin-activated fibrinolysis inhibitor (TAFI).
Tissue factor–dependent (extrinsic) pathway
Tissue factor (TF), or thromboplastin, is the primary activating moiety for the extrinsic pathway of coagulation. TF binds to factor VII and converts factor VII to factor VIIa. The resultant dimeric TF–factor VIIa complex then activates factors X and IX. TF is also a principal activator of factor IX. TF is expressed by cells of the subendothelium (smooth muscle cells, fibroblasts), whereas various stimuli may induce leukocytes and endothelial cells to express TF.
TF has a prominent role in the pathophysiology of DIC.  Production of TF is increased in infection. Endotoxin, tumor necrosis factor (TNF), interleukin-1 (IL-1), and other inflammatory mediators induce expression of TF in endothelial cells and monocytes, where only small amounts are normally expressed. Some evidence suggests that in sepsis-related DIC, TF and procoagulant-laden microparticles (MPs) are present in the circulation. 
Excessive release of TF is the primary mechanism involved in DIC resulting from trauma, especially head injury, and obstetric complications, which include intrauterine fetal demise, amniotic fluid embolism, and placental abruption. In trauma, tissue damage leads to release of TF and other tissue thromboplastins. Because of the rich TF content of brain tissue, massive head injuries are often complicated by DIC, and recent data suggest that brain trauma releases procoagulant-rich microparticles. 
Many malignancies are associated with cancer-derived procoagulants (CDP). TF is expressed on subcellular membrane vesicles termed plasma MPs. The procoagulant activity of these MPs was increased in patients in overt DIC with an underlying malignancy.  In acute promyelocytic leukemia (APL), CDP and TF are contained in multiple granules in the myeloblasts, which are responsible for the DIC commonly seen when chemotherapy results in leukemic cell lysis.  The use of differentiating agents in APL has significantly reduced this complication.
An uncommon source of thromboplastic activity is snake venom; some snake bites can lead to direct activation of factor X and hemorrhagic DIC.
Endothelial cells, monocytes and other cells produce and secrete a natural inhibitor of TF (ie, TF pathway inhibitor [TFPI]). The balance between TF and TFPI determines overall activity of the extrinsic pathway. Levels of TFPI are increased early in DIC; however, when overt DIC develops, the TF-to-TFPI ratio increases to the point that the extrinsic pathway is activated. Resolution of DIC results in a normalization of this ratio. 
Intrinsic (contact) pathway
Although the TF pathway is believed to be primary in the initiation of DIC, several instances in which the intrinsic pathway contributes to the pathophysiology of DIC are observed. Factor XII activation occurs in response to endotoxin, antigen-antibody complexes, fatty acids from fat embolism, burns, and extracorporeal circulation. In addition, factor XIIa leads to the activation of the complement system and generation of bradykinin. Increased levels of bradykinin may be responsible for hypotension observed in many forms of DIC.
Hypotensive shock and DIC may accompany severe hemolytic transfusion reactions. Immune complexes that form in such instances activate complement and initiate coagulation. Exposure of lipids normally residing on the internal surface of the erythrocyte plasma membrane may be involved in activation of the coagulation cascade.
Anticoagulant proteins C and S and antithrombin III also play a role in DIC. Congenital homozygous deficiencies of proteins C and S may result in neonatal DIC. Low levels of antithrombin III are noted during DIC, and infusion of antithrombin III concentrate may aid in the recovery from DIC.
The Ashwell receptor is a transmembrane glycoprotein on the vascular cell surface of hepatocytes. This receptor is involved in the clearance of prothrombotic factors and may mitigate sepsis-related DIC. 
Unregulated generation of thrombin and deposition of fibrin provide a strong stimulus to the fibrinolytic system. Whether fibrinolysis is a primary or secondary event is uncertain, but most believe that the fibrinolytic system is activated in response to the initiation of coagulation. In response to thrombin generation and endothelial injury, tPA is released from the endothelium. The continued activity of the fibrinolytic system contributes to the consumption of coagulation factors and to development of the hemorrhagic diathesis.
The incidence of DIC is unknown.
The DIC mortality rate varies depending on the underlying disorder and on the availability of supportive care. The overall mortality rate for children with sepsis-related DIC is 13-40%. In developing countries, this rate can exceed 90%.
No predilection for any race is known.
No predilection for either sex is known.
DIC occurs at any age.
A study by Chi and Ikezoe found that the median survival period in patients with non-Hodgkin lymphoma (NHL) and DIC was significantly less than in patients with NHL without DIC. The study, which involved 161 patients with NHL, 18 of whom were also diagnosed with DIC, found that the median length of survival in patients with DIC was 176 days, versus 2430 days in those without DIC, with the difference still being significant after the investigators adjusted for age, performance status, Ann Arbor stage, international prognostic index, and liver function panels. The study found worse liver function panels in patients with DIC, including with regard to values for bilirubin, aminotransferases, serum cholinesterase, and albumin, than in patients without DIC. 
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