Contents
DIC is an acquired syndrome characterised by the intravascular activation of coagulation with loss of localisation arising from different causes.
Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis (ISTH) definition of DIC
- MEDICAL EMERGENCY
- Type of consumption coagulopathy (all clotting factors consumed)
Etiology
Signature feature of DIC is the loss of localized activation of coagulation and the inefficiency of natural coagulation inhibitors to downregulate thrombin generation.
Pathophysiology
Consumptive coagulopathy:
Characterized by the systemic activation of blood coagulation, which generates intravascular thrombin and fibrin, resulting in the thrombosis of small- to medium-sized vessels and ultimately organ dysfunction and severe bleeding due to subsequent depletion of clotting factors.
Tissue factor (TF):
The critical mediator of DIC is the release of a transmembrane glycoprotein called tissue factor (TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon exposure to blood and platelets, TF binds with activated factor VIIa (normally present in trace amounts in the blood), forming the extrinsic tenase complex. This complex further activates factor IX and X to IXa and Xa, respectively, leading to the common coagulation pathway and the subsequent formation of thrombin and fibrin.
Thrombin generation in vivo:
Generation of thrombin in vivo is pivotal to haemostatic control by way of balancing both procoagulant and anticoagulant activities. Clot formation through the conversion of fibrinogen to fibrin is simultaneously controlled through activation by thrombin of the protein C anticoagulant regulatory pathway. This also serves several potential roles, including the walling off of pathogens, recruitment of cellular processes, and activation of appropriate endothelial response signals. This fine homeostatic balance of controlled thrombin generation is lost in DIC.
- Activation of intrinsic pathway of coagulation
- Reduction in levels of endogenous anticoagulant factors (for example, protein C, antithrombin)
- Increased availability of negatively charged phospholipid surfaces:externalisation of inner cellular membrane leafletcellular microparticle formationcirculating lipoproteins
Diverse and opposing effects of thrombin:
Interaction of inflammation and coagulation in DIC:
Once activated, the inflammatory and coagulation pathways interact with one another to amplify the response further. Whereas cytokines and pro-inflammatory mediators can induce coagulation, thrombin and other serine proteases interact with protease activated receptors on cell surfaces to promote further activation and additional inflammation.
Clinical features
Diagnosis
Diagnosis of DIC can be made by a combination of routinely available laboratory tests for coagulation, for which diagnostic algorithms have become available.
Acute DIC diagnostic algorithm:
ISTH subcommittee scoring system for overt DIC is a 5-step diagnostic algorithm to calculate a DIC score based on simple laboratory results. For a diagnosis of overt DIC, a score of ≥ 5 from 4 parameters are required
Peripheral blood smear (PBS):
Differential diagnosis:
Management
Key factor in DIC management is the proper treatment of the underlying cause and that may itself revert or prevent the development of DIC. But sometimes additional supportive treatment aimed at correction of coagulation abnormalities may be required.
- Remove causative factor: mainstay of management of DIC is to specifically remove the underlying causative factor. H
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