Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is characterized by systemic activation of blood coagulation, which results in generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to multiple organ dysfunction syndrome. Consumption of clotting factors and platelets in DIC can result in life-threatening haemorrhage.

 It is a thrombo-haemorrhagic disorder.

 Explained by two different ways of thrombin generation:

• extremely rapid burst of excess thrombin production led to a “hyper fibrinolytic” form of DIC.
• gradual, but still excess, amounts of thrombin lead to a “procoagulant” form of DIC.

DIC usually results from exposure of tissue factor in the peripheral blood, triggering the extrinsic pathway of coagulation. The causes of DIC can be classified into several groups of disorders, the more common being:

• Severe infections: Gram-negative lipopolysaccharides and Gram-positive peptidoglycan, which cause generation or exposure of tissue factor activity in phagocytic, endothelial and tissue cells.
• Malignant disorders (particularly acute promyelocytic leukemia): tumour cells express or release tissue factor.
• Shock of any cause: in ischemic tissues, there is high exposure and release of tissue factor.
• Severe transfusion reactions.
• Vascular abnormalities – Kasabach-Merritt syndrome and large vascular aneurysms.
• Severe hepatic failure.

Epidemiology and prognosis

Disseminated intravascular coagulation (DIC) can manifest in 30-50% of patients with sepsis and is estimated to affect 1% of all hospitalized individuals, cutting across all age groups, races, and showing no particular predisposition towards any sex. The prognosis of DIC largely hinges on the underlying medical condition. For instance, idiopathic purpura fulminans linked with DIC carries a mortality rate of 18%. In cases of septic abortion complicated by clostridial infection and shock alongside severe DIC, the mortality rate spikes to 50%. Moreover, within the context of major trauma, the incidence of DIC approximately doubles the mortality risk, underscoring the critical impact of this condition on patient outcomes.

Clinical Features

The clinical presentation of DIC is usually related to the underlying inciting condition.

• In acute DIC: bleeding often associated with simultaneous microvascular thromboses may lead to dysfunction and multiorgan failure, while mechanical disruption of red blood cells produces schistocytes and mild intravascular haemolysis (up to thrombotic thrombocytopenic purpura and haemolytic–uremic syndrome).

Bleeding involves at least three unrelated sites (ears, nose and throat, gastrointestinal and respiratory tract, site of venipuncture or i.v. infusion).

Laboratory Tests

No laboratory tests or combination of tests can unequivocally confirm the diagnosis of DIC. Several scoring systems have been proposed. According to the International Society on Thrombosis and Haemostasis (ISTH) guidelines, a laboratory diagnosis of DIC can be made by scoring:

DIC can be diagnosed if a patient affected by an underlying disorder known to be DIC-related has a total score ≥5.

If the score is <5, laboratory tests should be repeated.

However, the laboratory tests used to diagnose DIC require an understanding of the underlying disease and the patient’s clinical status.

• D-dimer test is a sensitive but non-specific test, potentially altered in many other clinical conditions including recent surgery, ascites, pleural effusion, soft-tissue bleeding and inflammation.
• Underlying defects in protein synthesis (liver dysfunction, vitamin K deficiency) or other causes of thrombocytopenia (marrow replacement by tumour or effect of chemotherapy) may complicate laboratory findings.

Management

• Management of the underlying disorder.
• Treatment of thrombocytopenia in a setting of low platelet count.
• Cryoprecipitate (8–10 U) in bleeding manifestations if fibrinogen level is <1 g/l.
• 1–2 U fresh frozen plasma to replace other haemostatic components, according with the severity of the depletion.
• The role of heparin is controversial. Heparin is beneficial in the treatment of slowly evolving DIC with venous thrombosis or pulmonary embolism but is not indicated in acute DIC with bleeding or bleeding risk (except in women with a retained dead foetus and evolving DIC).
• Antithrombin concentrate has been tested in clinical trials; however, its potential role in DIC therapy is still under investigation.

References

• Costello RA, Nehring SM. Disseminated Intravascular Coagulation (DIC). 2018 Jan. 
• Vincent JL, De Backer D. Does disseminated intravascular coagulation lead to multiple organ failure?. Crit Care Clin. 2005 Jul. 21(3):469-77. 
• Papageorgiou C, Jourdi G, Adjambri E, Walborn A, Patel P, Fareed J, et al. Disseminated Intravascular Coagulation: An Update on Pathogenesis, Diagnosis, and Therapeutic Strategies. Clin Appl Thromb Hemost. 2018 Oct 8. 1076029618806424.
• Mariano P. (2016). ESMO Handbook of Oncological Emergencies. 2nd edition. Switzerland: ESMO press