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Disseminated Intravascular Coagulation (DIC)

(Consumption Coagulopathy; Defibrination Syndrome)


Joel L. Moake

, MD, Baylor College of Medicine

Last full review/revision Jan 2020| Content last modified Jan 2020

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 partial thromboplastin time and prothrombin time, increased levels of plasma D-dimers (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.

(See also Overview of Coagulation Disorders.)

Etiology of DIC

Disseminated intravascular coagulation usually results from exposure of tissue factor to blood, initiating the coagulation cascade. In addition, the fibrinolytic pathway is activated in DIC (see figure Fibrinolytic pathway). Stimulation of endothelial cells by cytokines and perturbed microvascular blood flow causes the release of tissue plasminogen activator (tPA) from endothelial cells. Both tPA and plasminogen attach to fibrin polymers, and plasmin (generated by tPA cleavage of plasminogen) cleaves fibrin into D-dimers and other fibrin degradation products. DIC can, therefore, cause both thrombosis and bleeding (if the consumption of platelets and/or coagulation factors is excessive)

Fibrinolytic pathway

Fibrinolytic pathway

DIC occurs most often in the following clinical circumstances:

  • Complications of obstetrics (eg, abruptio placentae, saline-induced therapeutic abortion, retained dead fetus or products of conception, amniotic fluid embolism): Placental tissue with tissue factor activity enters or is exposed to the maternal circulation.
  • Infection, particularly with gram-negative organisms: Gram-negative endotoxin causes generation or exposure of tissue factor activity in phagocytic, endothelial, and tissue cells.
  • Cancer, particularly mucin-secreting adenocarcinomas of the pancreas, adenocarcinomas of the prostate, and acute promyelocytic leukemia: Tumor cells express and expose (or release) tissue factor.
  • Shock due to any condition that causes ischemic tissue injury and exposure or release of tissue factor.

Less common causes of DIC include

  • Severe tissue damage due to 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
  • Enzymes in certain snake venoms that enter the circulation, activate one or several coagulation factors, and either generate thrombin or directly convert fibrinogen to fibrin
  • Profound intravascular hemolysis
  • Aortic aneurysms or cavernous hemangiomas (Kasabach-Merritt syndrome) associated with vessel wall damage and areas of blood stasis

Slowly-evolving disseminated intravascular coagulation typically results mainly from cancer, aneurysms, or cavernous hemangiomas.

Pathophysiology of DIC

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, depletion of plasma coagulation factors and fibrinogen, and 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.

Symptoms and Signs of DIC

In slowly evolving disseminated intravascular coagulation, symptoms of venous thrombosis and/or symptoms of 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 of DIC

  • Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), plasma fibrinogen, plasma D-dimer

Disseminated intravascular coagulation 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 levels (an indication of in vivo fibrin polymer generation and degradation) are obtained.

Slowly evolving DIC

Slowly evolving DIC produces

  • Mild thrombocytopenia
  • Normal to minimally prolonged PT (results are typically reported as international normalized ratio [INR]) and PTT
  • Normal or moderately reduced fibrinogen level
  • 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.

Rapidly evolving DIC

Rapidly evolving DIC results in

  • More severe thrombocytopenia
  • More prolonged PT and PTT
  • Rapidly declining plasma fibrinogen level
  • 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 hepatic endothelial cells, and released as they are destroyed; factor VIII is reduced in DIC because of the thrombin-induced generation of activated protein C, which proteolyses the activated form of factor VIII.

Treatment of DIC

  • Treatment of cause
  • Possibly replacement therapy (eg, platelets, cryoprecipitate, fresh frozen plasma))
  • Sometimes heparin

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, disseminated intravascular coagulation should subside quickly.

Severe bleeding

If bleeding is severe or involves a critical location (eg, brain, gastrointestinal tract), or if there is an urgent need for surgery, then adjunctive replacement therapy is indicated. Replacement may consist of

  • Platelet concentrates to correct thrombocytopenia (in case of rapidly declining platelet count or platelets < 10,000 to 20,000/microL [< 10 to 20 ×109/L])
  • Cryoprecipitate to replace fibrinogen (and factor VIII) if the fibrinogen level is declining rapidly or is < 100 mg/dL (< 2.9 micromol/L).
  • 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. Volume replacement when hypotension is present is essential to arrest the DIC.

Slowly evolving DIC

Heparin is useful in the treatment of slowly evolving disseminated intravascular coagulation with venous thrombosis or pulmonary embolism. Heparin usually is not indicated in rapidly evolving DIC with bleeding or bleeding risk. An exception is in women with a retained dead fetus and evolving DIC with a progressive decrease in platelets, fibrinogen, and coagulation factors. In these latter patients, heparin is given 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.

Key Points

  • In disseminated intravascular coagulation (DIC), coagulation is usually activated when blood is exposed to tissue factor. In association with coagulation, the fibrinolytic pathway is also activated.
  • DIC usually begins rapidly and causes bleeding and microvascular occlusion, leading to organ failure.
  • DIC sometimes begins slowly and causes thromboembolic phenomena rather than bleeding.
  • Severe, rapid-onset DIC causes severe thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, a rapidly declining plasma fibrinogen level, and a high plasma D-dimer level.
  • Immediate correction of the cause is the priority; severe bleeding may also require replacement therapy with platelets, cryoprecipitate (containing fibrinogen), and fresh frozen plasma (containing other coagulation factors).
  • Heparin is useful in slow-onset DIC, but rarely in DIC of rapid onset (except in women with a retained dead fetus).

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