Disseminated Intravascular Coagulation

Disseminated Intravascular Coagulation GB Young, Western University, London, ON, Canada r 2014 Elsevier Inc. All rights reserved.

Definition Disseminated intravascular coagulation (DIC) is a syndrome relating to multifocal deposition of fibrin in medium–small blood vessels, often coupled with the depletion of platelets and coagulation factors, leading to increased bleeding tendencies.

Pathogenesis DIC is due to activation of the intrinsic coagulation pathway, leading to the production of thrombin and then fibrin deposition in medium and small blood vessels. The fibrinolytic system is inhibited, which amplifies the fibrin deposition. Because of the consumption of coagulation factors and platelet uptake and destruction, bleeding tendencies can result (Figure 1). Table 1 lists various conditions that have been known to trigger DIC likely via various mechanisms, but often involving inflammatory cytokines.

Clinical Manifestations from Disseminated Intravascular Coagulation DIC is most commonly a systemic disorder, but some organs, including the brain, can be affected to a greater

degree than others. Multifocal ischemic strokes can produce multifocal neurological deficits, coma, or seizures. These can fluctuate due to the ongoing dynamic process. Most commonly the brain suffers from the underlying systemic inflammatory response syndrome or the effects of other organ failure. Bleeding is common in DIC and may manifest with easy bruising, bleeding from puncture sites or major ecchymoses, or gastrointestinal bleeding.

Diagnosis of Disseminated Intravascular Coagulation The diagnosis of DIC requires a combined clinical–laboratory strategy. The clinical picture along with rapid decrease in platelet count, prolongation of international normalized ratio, prothrombin time or partial thromboplastin time, the presence of fibrin degradation products or D-dimers, and, in advanced cases, decreased fibrinogen concentration in the blood is strongly supportive of the diagnosis of DIC. Decreased antithrombin III or protein C can also be helpful. DIC and severe liver disease are both associated with similar bleeding tendencies, with decrease in coagulation factors and platelets, but the clinical picture of severe liver failure is usually obvious. Thrombotic thrombocytopenic purpura (TTP) and hemolytic–uremic syndrome (HUS) are usually associated with more hemolysis, elevation of lactic acid dehydrogenase in the serum, and more fragmentation of red blood cells on blood smears, although the latter can be found in DIC. Fibrin split products and lower fibrinogen concentrations are more suggestive of DIC than TTP or HUS.

Tissue factor

Table 1 Clinical conditions associated with disseminated intravascular coagulation Infections Bacteria (both Gram negative and Gram positive) Viral Protozoal Rickettsia

Activation of intrinsic pathway (aFVII, fibrin formation) and inhibition of anticoagulation pathways (antithrombin III, protein C, and TFPI)

Intravascular thrombosis

Consumption of platelets and coagulation factors: bleeding

Figure 1 Disseminated intravascular coagulation. aFVII, activated Factor VII; TFPI, tissue factor pathway inhibitor.

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Tissue damage Trauma Burns Surgery Dissecting aneurysm Neuroleptic malignant syndrome Acute necrosis of brain tissue

Obstetrical complications Amniotic fluid embolism Abruptio placentae Cancer and tumors Myeloproliferative disorders Various solid tumors Leukemia Giant hemangioma (Kasabach–Merritt syndrome) Immunological disorders Severe allergic reactions Transfusion reactions Transplant rejection

Reactions to toxins Snake venom Amphetamines

Encyclopedia of the Neurological Sciences, Volume 1

doi:10.1016/B978-0-12-385157-4.00327-4

Disseminated Intravascular Coagulation

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Management

Further Reading

The best management is treatment/irradication of the underlying trigger or disorder. Excessive bleeding often requires fresh frozen plasma, whereas acrocyanosis or incipient gangrene requires anticoagulation with heparin. Trials using activated protein C have not been impressive.

Levi M and Ten Cate H (1999) Disseminated intravascular coagulation. New England Journal of Medicine 341: 586–592. Longo DL, Fauci AS, Kasper DL, and Hauser SL (eds.) (2012) Harrison’s Principles of Internal Medicine, 18th edn., ch. 116, pp. 978–980. New York: McGraw Hill. Weiss DJ and Rashid J (1998) The sepsis-coagulant axis: A review. Journal of Veterinary Internal Medicine 12: 317–324.

See also: Cerebral Venous Thrombosis. Coagulopathies and Stroke. Sepsis-Associated Encephalopathy