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Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation factor consumption occur. DIC that evolves slowly (over weeks or months) causes primarily venous thrombotic and embolic manifestations; DIC that evolves rapidly (over hours or days) causes primarily bleeding. Severe, rapidly evolving DIC is diagnosed by demonstrating thrombocytopenia, an elevated PTT and PT, increased levels of plasma d-dimer (or serum fibrin degradation products), and a decreasing plasma fibrinogen level. Treatment includes correction of the cause and replacement of platelets, coagulation factors (in fresh frozen plasma), and fibrinogen (in cryoprecipitate) to control severe bleeding. Heparin is used as therapy (or prophylaxis) in patients with slowly evolving DIC who have (or are at risk of) venous thromboembolism.
Etiology
DIC usually results from exposure of tissue factor to blood, initiating the coagulation cascade (see Fig. 2: Hemostasis: Fibrinolytic pathway. ). DIC occurs in the following clinical circumstances:
Less common causes of DIC include severe tissue damage from head trauma, burns, frostbite, or gunshot wounds; complications of prostate surgery that allow prostatic material with tissue factor activity (along with plasminogen activators) to enter the circulation; venomous snake bites in which enzymes enter the circulation, activate one or several coagulation factors, and either generate thrombin or directly convert fibrinogen to fibrin; profound intravascular hemolysis; and aortic aneurysms or cavernous hemangiomas (Kasabach-Merritt syndrome) associated with vessel wall damage and areas of blood stasis.
Pathophysiology
Slowly evolving DIC primarily causes venous thromboembolic manifestations (eg, deep venous thrombosis, pulmonary embolism), although occasionally cardiac valve vegetations occur; abnormal bleeding is uncommon.
Severe, rapidly evolving DIC, in contrast, causes thrombocytopenia and depletion of plasma clotting factors and fibrinogen, which cause bleeding. Bleeding into organs, along with microvascular thromboses, may cause dysfunction and failure in multiple organs. Delayed dissolution of fibrin polymers by fibrinolysis may result in the mechanical disruption of RBCs, producing schistocytes and mild intravascular hemolysis (see Thrombocytopenia and Platelet Dysfunction: Thrombotic Thrombocytopenic Purpura (TTP) and Hemolytic-Uremic Syndrome (HUS)).
Symptoms and Signs
In slowly evolving DIC, symptoms of venous thrombosis (see Peripheral Venous Disorders: Deep Venous Thrombosis (DVT)) and pulmonary embolism (see Pulmonary Embolism) may be present.
In severe, rapidly evolving DIC, skin puncture sites (eg, IV or arterial punctures) bleed persistently, ecchymoses form at sites of parenteral injections, and serious GI bleeding may occur.
Diagnosis
DIC is suspected in patients with unexplained bleeding or venous thromboembolism, especially if a predisposing condition exists. If DIC is suspected, platelet count, PT, PTT, plasma fibrinogen level, and plasma d-dimer level (an indication of in vivo fibrin deposition and degradation) are obtained.
Slowly evolving DIC produces mild thrombocytopenia, a normal to minimally prolonged PT (results are typically reported as INR) and PTT, a normal or moderately reduced fibrinogen level, and an increased plasma d-dimer level. Because various disorders stimulate increased synthesis of fibrinogen as an acute-phase reactant, a declining fibrinogen level on 2 consecutive measurements can help make the diagnosis of DIC. Initial PTT values in slowly evolving DIC may actually be shorter than normal, probably because of the presence of activated coagulation factors in the plasma.
Severe, rapidly evolving DIC results in more severe thrombocytopenia, more prolonged PT and PTT, a rapidly declining plasma fibrinogen level, and a high plasma d-dimer level.
A factor VIII level can sometimes be helpful if severe, acute DIC must be differentiated from massive hepatic necrosis, which can cause similar abnormalities in coagulation studies. The factor VIII level is elevated in hepatic necrosis, because factor VIII is made in hepatocytes and released as they are destroyed; factor VIII is reduced in DIC because of the thrombin-induced generation of activated protein C, which proteolyses factor VIII.
Treatment
Immediate correction of the cause is the priority (eg, broad-spectrum antibiotic treatment of suspected gram-negative sepsis, evacuation of the uterus in abruptio placentae). If treatment is effective, DIC should subside quickly. If bleeding is severe, adjunctive replacement therapy is indicated, consisting of platelet concentrates to correct thrombocytopenia; cryoprecipitate to replace fibrinogen and factor VIII; and fresh frozen plasma to increase levels of other clotting factors and natural anticoagulants (antithrombin, proteins C, S, and Z). The effectiveness of infusion of concentrates of antithrombin in severe, rapidly evolving DIC is unresolved.
Heparin is useful in the treatment of slowly evolving DIC with venous thrombosis or pulmonary embolism. Heparin usually is not indicated in rapidly evolving DIC with bleeding or bleeding risk, except in women with a retained dead fetus and evolving DIC with a progressive decrease in platelets, fibrinogen, and coagulation factors. In these patients, heparin is administered for several days to control DIC, increase fibrinogen and platelet levels, and decrease excessive coagulation factor consumption. Heparin is then stopped and the uterus evacuated.
Last full review/revision June 2009 by Joel L. Moake, MD
Content last modified January 2013
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