The syndrome of disseminated intravascular coagulation (ICD): causes, symptoms, diagnosis, treatment

The syndrome of disseminated intravascular coagulation (ICE, consumption coagulopathy, defibrillation syndrome) is a disorder with pronounced generation of thrombin and fibrin in the circulating blood. During this process, there is an increased aggregation of platelets and the consumption of clotting factors. ICE, which proceeds slowly (weeks or months), causes predominantly venous thrombosis and embolism; ICE that occurs suddenly (hours or days) is manifested primarily by bleeding. A severe, sudden-onset DVS is diagnosed with thrombocytopenia, increased TTH and PV, increased levels of fibrin degradation products and reduced fibrinogen levels. Treatment includes correction of the underlying cause of the internal combustion engine and the replacement of platelets, coagulation factors (fresh frozen plasma) and fibrinogen (cryoprecipitate) to control severe bleeding. Heparin is used as a therapy (prophylaxis) of hypercoagulation in patients with slowly developing ICE, in whom venous thromboembolism has developed (or is at risk).

Causes of the dIC-Syndrome

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

• obstetric complications, for example placental abruption; medical abortion induced by saline;
• intrauterine fetal death; embolism of the amniotic fluid. The influx of placental tissue with the activity of the tissue factor in the mother's bloodstream;
• infection, especially caused by gram-negative microorganisms. Gram-negative endotoxin generates tissue factor activity in phagocytes, endothelial and tissue cells;
• tumors, especially mucin-producing pancreatic and prostatic adenocarcinomas, pro-myelocytic leukemia that expose and release tissue factor activity;
• shock caused by any cause that leads to ischemic tissue damage and the release of tissue factor.

A more rare cause of ICE is severe tissue damage in head injuries, burns, frostbites, or gunshot wounds; complications in operations on the prostate gland with the release of a prostatic material with tissue factor (with plasminogen activators) into circulation; bites of poisonous snakes, 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 (Kazabaha-Merritt syndrome), associated with damage to the vascular wall and the stasis zone of the blood.

Slowly developing DIC is mainly manifested by a clinic of venous thromboembolism (for example, deep vein thrombosis, pulmonary embolism), sometimes there is a vegetation of the mitral valve; manifestations of severe bleeding are uncharacteristic. In contrast, with severe, sudden-onset DVS, bleeding occurs due to thrombocytopenia and a decrease in plasma clotting and fibrinogen levels. Bleeding to the organs together with microvascular thrombosis can cause hemorrhagic necrosis of the tissue.

[1], [2], [3], [4], [5], [6]

Symptoms of the dIC-Syndrome

With the slow development of ICE, manifestations can consist in the development of venous thrombosis and pulmonary embolism.

In severe, suddenly developing ICE, there is continuous bleeding of the puncture sites of the skin (for example, intravenous or arterial punctures), hemorrhages in the places of parenteral injections, severe gastrointestinal bleeding is possible. The delayed destruction of fibrin fibers by the fibrinolysis system can lead to mechanical destruction of erythrocytes and easily expressed intravascular hemolysis. Sometimes microvascular thrombosis and hemorrhagic necrosis lead to organ dysfunction and multiple organ failure.

[7], [8], [9], [10]

Diagnostics of the dIC-Syndrome

DIC is suspected in patients with unexplained hemorrhage or venous thromboembolism. In such cases, the following studies are performed: the number of platelets, PV, TCH, fibrinogen and plasma D-dimer levels (indicate fibrin deposition and degradation).

Slowly developing DIC causes mild thrombocytopenia, normal or minimally increased prothrombin time (the result is usually MHO) and TCH, normal or moderately reduced fibrinogen synthesis and elevated plasma D-dimer levels. Since, in various diseases, an increase in the synthesis of fibrinogen as an acute phase marker is stimulated, the determination of a decrease in the level of fibrinogen in two consecutive measurements can help in the diagnosis of ICE.

A severe, sudden development of ICE leads to deeper thrombocytopenia, a more pronounced increase in PT and TCH, a rapid decrease in the plasma fibrinogen concentration and a high plasma D-dimer level.

Determination of the level of factor VIII can be useful if it is necessary to differentiate a heavy, acute ICE from massive liver necrosis, which can lead to similar deviations in the coagulogram. The level of factor VIII may increase with liver necrosis, since factor VIII is produced in hepatocytes and released when they are destroyed; in DIC, the level of factor VIII decreases, since thrombin-induced generation of activated protein C leads to proteolysis of factor VIII.

[11], [12], [13]

Treatment of the dIC-Syndrome

Rapid correction of the underlying cause is a priority (for example, broad-spectrum antibiotics for suspected Gram-negative sepsis, removal of the uterus with placental abruption). With effective treatment of ICE quickly subsides. With severe bleeding, adequate replacement therapy is necessary: platelet mass for correcting thrombocytopenia; cryoprecipitate for the replacement of 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 an antithrombin concentrate or activated protein C in a severe, rapidly developing ICE is currently being studied.

The administration of heparin is usually not indicated in ICE, except in cases of intrauterine fetal death in women and the development of ICE with a progressive decrease in platelet levels, fibrinogen and coagulation factors. In these circumstances, heparin is used for several days to control ICE, increase fibrinogen and platelet levels, reduce the rapid consumption of clotting factors before removal of the uterus.