Disseminated intravascular coagulation syndrome (DIC): causes, symptoms, diagnosis, treatment

Disseminated intravascular coagulation (DIC, consumption coagulopathy, defibrination syndrome) is a disorder with pronounced generation of thrombin and fibrin in the circulating blood. During this process, increased platelet aggregation and consumption of coagulation factors occur. DIC that develops slowly (weeks or months) causes predominantly venous thrombosis and embolic manifestations; DIC that occurs suddenly (hours or days) manifests itself primarily as bleeding. Severe, sudden-onset DIC is diagnosed in the presence of thrombocytopenia, prolonged PTT and PT, elevated levels of fibrin degradation products, and decreased fibrinogen. Treatment includes correction of the underlying cause of DIC and replacement of platelets, coagulation factors (fresh frozen plasma), and fibrinogen (cryoprecipitate) to control severe bleeding. Heparin is used as a therapy (prophylaxis) for hypercoagulation in patients with slowly developing DIC who have developed (or are at risk of developing) venous thromboembolism.

Causes DIC

DIC is usually the result of tissue factor being released into the blood, which initiates the coagulation cascade. DIC occurs in the following clinical situations:

• obstetric complications such as placental abruption; saline-induced medical abortion;
• intrauterine fetal death; amniotic fluid embolism. Entry of placental tissue with tissue factor activity into the maternal bloodstream;
• infections, especially those caused by gram-negative microorganisms. Gram-negative endotoxin generates tissue factor activity in phagocytes, endothelial and tissue cells;
• tumors, especially mucin-producing adenocarcinomas of the pancreas and prostate, promyelocytic leukemia, which expose and release tissue factor activity;
• shock caused by any cause that results in ischemic tissue injury and release of tissue factor.

Less common causes of DIC include severe tissue damage from head trauma, burns, frostbite, or gunshot wounds; complications of prostate surgery with release of prostatic material with tissue factor activity (plasminogen activators) into the circulation; snake bites, in which enzymes enter the bloodstream and activate one or more coagulation factors and generate thrombin or directly convert fibrinogen to fibrin; severe intravascular hemolysis; aortic aneurysm or cavernous hemangioma (Kasabach-Merritt syndrome) associated with damage to the vascular wall and an area of blood stasis.

Slowly developing DIC is predominantly manifested by the clinical picture of venous thromboembolism (e.g. deep vein thrombosis, pulmonary embolism), sometimes vegetation of the mitral valve is encountered; manifestations of severe bleeding are uncommon. In contrast, with severe, suddenly developing DIC, bleeding develops due to thrombocytopenia and a decrease in the levels of plasma coagulation factors and fibrinogen. Bleeding into organs together with microvascular thromboses can cause hemorrhagic tissue necrosis.

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Symptoms DIC

With slow development of DIC, manifestations may include the development of venous thrombosis and pulmonary embolism.

In severe, suddenly developing DIC, there is continuous bleeding from skin puncture sites (e.g., intravenous or arterial punctures), hemorrhages at parenteral injection sites, and severe gastrointestinal bleeding is possible. Slow destruction of fibrin fibers by the fibrinolysis system can lead to mechanical destruction of red blood cells and mild intravascular hemolysis. Sometimes microvascular thrombosis and hemorrhagic necrosis lead to organ dysfunction and multiple organ failure.

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Diagnostics DIC

DIC is suspected in patients with unexplained bleeding or venous thromboembolism. In such cases, the following tests are performed: platelet count, PT, PTT, fibrinogen level and plasma D-dimer (indicating fibrin deposition and degradation).

Slowly evolving DIC causes mild thrombocytopenia, normal or minimally increased prothrombin time (the result is usually presented as INR) and PTT, normal or moderately decreased fibrinogen synthesis, and increased plasma D-dimer levels. Because various diseases stimulate increased fibrinogen synthesis as an acute phase marker, detecting decreased fibrinogen levels on two consecutive measurements may aid in the diagnosis of DIC.

Severe, abruptly developing DIC results in more profound thrombocytopenia, a more pronounced increase in PT and PTT, a rapid decrease in plasma fibrinogen concentration, and high plasma D-dimer levels.

Factor VIII levels may be useful in differentiating severe, acute DIC from massive liver necrosis, which can cause similar coagulation abnormalities. Factor VIII levels may be elevated in liver necrosis because factor VIII is produced in hepatocytes and released when they are destroyed; in DIC, factor VIII levels are decreased because thrombin-induced generation of activated protein C leads to proteolysis of factor VIII.

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Treatment DIC

Rapid correction of the underlying cause is a priority (e.g., broad-spectrum antibiotics for suspected gram-negative sepsis, hysterectomy for placental abruption). With effective treatment, DIC quickly subsides. In cases of severe bleeding, adequate replacement therapy is necessary: platelet mass to correct thrombocytopenia; cryoprecipitate to replace fibrinogen and factor VIII; fresh frozen plasma to increase the level of other coagulation factors and natural anticoagulants (antithrombin, protein C and S). The effectiveness of infusion of antithrombin concentrate or activated protein C in severe, rapidly developing DIC is currently under study.

Heparin is not usually indicated in DIC, except in cases of intrauterine fetal death in women and established DIC with progressive decline in platelet, fibrinogen, and coagulation factor levels. In these circumstances, heparin is given for several days to control DIC, increase fibrinogen and platelet levels, and reduce rapid consumption of coagulation factors before hysterectomy.