Disseminated intravascular coagulation (DIC) is an acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors. Thrombi may lead to vascular obstruction/ischaemia and multi-organ failure. Spontaneous bleeding may occur.

Causes

Disease states that trigger systemic activation of coagulation may lead to DIC. Causes include

• Sepsis/severe infection, major trauma or burns
• Some malignancies (acute myelocytic leukaemia or metastatic mucin-secreting adenocarcinoma)
• Obstetric disorders (amniotic fluid embolism, eclampsia, abruptio placentae, retained dead fetus syndrome)
• Severe organ destruction or failure (severe pancreatitis, acute hepatic failure)
• Vascular disorders (Kasabach-Merritt syndrome or giant haemangiomas, large aortic aneurysms)
• Severe toxic or immunological reactions (blood transfusion reaction or haemolytic reactions, organ transplant rejection, snake bite)

Pathophysiology

Disseminated intravascular coagulation (DIC) is characterised by a widespread inappropriate intravascular deposition of fibrin with consumption of coagulation factors and platelets. This may occur as a consequence of many disorders that release procoagulant material into the circulation or cause widespread endothelial damage or platelet aggregation. Increased activity of thrombin in the circulation overwhelms its normal rate of removal by natural anticoagulants. In addition to causing increased deposition of fibrin in the microcirculation and widespread platelet aggregation to the vessels, intravascular thrombin formation interferes with fibrin polymerisation. Intense fibrinolysis is stimulated by thrombi on vascular walls and the release of fibrin degradation products again interferes with fibrin polymerisation. The combined action of thrombin and plasmin causes depletion of fibrinogen and all coagulation factors, compounded by thrombocytopaenia caused by platelet consumption.

Clinical features

Common findings include thrombosis, bleeding, or both. In general, ischaemic findings are considered earlier signs of DIC, while bleeding findings are late overt signs. Bleeding from at least three unrelated sites is typical.

Haemorrhagic features:

• Petechiae/ecchymosis
• Oozing at wound or venepuncture sites
• Bleeding from ears, nose or throat
• Haematuria
• Haemoptysis
• Gastrointestinal bleeding
• Intracranial bleeding

Ischaemic features:

• Oliguria/hypotension/tachycardia/circulatory collapse
• Purpura fulminans, gangrene or acral cyanosis
• Delirium/coma

Laboratory findings:

• Initial laboratory investigations:
  • Platelet count: thrombocytopaenia
  • Fibrinogen: low levels
  • Prothrombin time (PT)/Activated partial thromboplastin time (aPTT): prolonged
  • D-dimer/fibrin degradation products (FDPs): elevated
• Additional tests:
  • Thrombin time (TT): prolonged
  • Coagulation factors (V, VIII, X, XIII): low levels

Management

• Treatment of the underlying disorder
  • Active treatment of the underlying disorder stops the triggering process.
• Restoration of physiological coagulation pathways
  • Normal coagulation can be restored by inhibition of overactive coagulation pathways and enhancement of suppressed anticoagulation systems.
  • Heparin can be considered for this purpose; it inhibits the coagulation cascade and prevents further thrombogenesis by enhancing the effect of antithrombin III. Thus, normal levels of antithrombin III are a prerequisite for heparin to be effective.
  • Heparin may be indicated in selected patients with dominant symptoms and signs of thrombosis without evidence of significant bleeding, especially in the case of chronic DIC. Heparin use is not advocated in patients at high risk of bleeding because it may worsen the bleeding problems associated with DIC.
• Replacement therapy
  • The aim of replacement therapy in DIC is to replace the deficient platelets and coagulation factors. Replacement of platelets and coagulation factors is indicated only in patients:
    • With active bleeding
    • Requiring an invasive procedure
    • At risk for bleeding complications
    • With a documented deficiency of platelets and/or coagulation factors/inhibitors
  • Fresh frozen plasma (FFP) and platelet concentrates are the 2 common blood components used to replace the deficient platelets and coagulation factors. FFP can provide coagulation factors and fibrinogen, as well as coagulation inhibitors in balanced amounts. Other blood products, such as cryoprecipitates and fibrinogen concentrates, may be considered, but FFP is preferable in the setting of DIC because it provides balanced coagulation factors and inhibitors.
• Antifibrinolytic agents
  • Antifibrinolytic agents, such as aminocaproic acid and tranexamic acid, should be used with extreme caution because they inhibit the fibrinolytic pathways, which may worsen the symptoms and signs of thrombosis.
  • They are occasionally used in patients with severe refractory bleeding resistant to conventional replacement therapy or in patients with hyperfibrinolysis associated with acute promyelocytic leukemia and other forms of cancer.