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Hematological System

Disseminated intravascular coagulation (DIC)

Acquired clinicobiological syndrome characterized by widespread activation of coagulation leading to fibrin deposition in the vasculature, organ dysfunction, consumption of clotting factors and platelets, and life-threatening hemorrhage.

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.

Conditions associated with DIC
Conditions associated with DIC | Venugopal A. (2014). Disseminated intravascular coagulation. Indian journal of anaesthesia, 58(5), 603–608. https://doi.org/10.4103/0019-5049.144666

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.
Bleeding, organ failure, massive bleeding, and non-symptomatic types of DIC
Bleeding, organ failure, massive bleeding, and non-symptomatic types of DIC | Wada, H., Matsumoto, T., & Yamashita, Y. (2014). Diagnosis and treatment of disseminated intravascular coagulation (DIC) according to four DIC guidelines. Journal of Intensive Care, 2(1), 15. https://doi.org/10.1186/2052-0492-2-15

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.
Generation and dissemination of thrombin
Generation and dissemination of thrombin. I: normal, localised coagulation activation, via extrinsic and intrinsic pathways, to generate thrombin with a resultant balance in procoagulant conversion of fibrinogen to fibrin and anticoagulant activation of protein C (PC) to its activated form, APC. The orange area denotes the reactions that are highly dependent on phospholipid surfaces. II: compensated increase in coagulation activation with contribution from endothelial, monocyte, and platelet cell surfaces. Arrows denote the intensity of the stress or acute phase response. III: decompensation and dissemination of thrombin generation in vivo, with increased anionic phospholipid surfaces provided by circulating microparticles and lipoproteins released as part of the stress response | Toh, C. H., & Dennis, M. (2003). Disseminated intravascular coagulation: old disease, new hope. BMJ (Clinical research ed.), 327(7421), 974–977. https://doi.org/10.1136/bmj.327.7421.974
  • 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:

Diverse and opposing effects of thrombin
Diverse and opposing effects of thrombin:: Excess thrombin generation in DIC leads to bleeding and/or thrombosis depending on the dominant change affecting the dynamic balance in both coagulant and fibrinolytic consequences. | Disseminated intravascular coagulation. (2016). Nature Reviews Disease Primers, 2, 16038. Retrieved from http://dx.doi.org/10.1038/nrdp.2016.38

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.
Generalized interrelationship between the initiation of coagulation, complement activation, and the inflammatory response.
Generalized interrelationship between the initiation of coagulation, complement activation, and the inflammatory response. | Benjamin M. Boral, DO, Dennis J. Williams , MD, Leonard I. Boral, MD, MBA, Disseminated Intravascular Coagulation, American Journal of Clinical Pathology, Volume 146, Issue 6, December 2016, Pages 670–680, https://doi.org/10.1093/ajcp/aqw195

Clinical features

Disseminated intravascular coagulation (DIC)
Purpura fulminans in a patient with DIC due to meningococcal septicaemia
Purpura fulminans in a patient with DIC due to meningococcal septicaemia. Shoulder (part a) and hand (part b). | Disseminated intravascular coagulation: old disease, new hope, Toh, C. H. & Dennis, M., 327, 974–977, 2003 with permission from BMJ Publishing Group Ltd.

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
Diagnostic algorithm for DIC, proposed by ISTH
Diagnostic algorithm for DIC, proposed by ISTH | Venugopal A . (2014). Disseminated intravascular coagulation. Indian journal of anaesthesia, 58(5), 603–608. https://doi.org/10.4103/0019-5049.144666

Peripheral blood smear (PBS):

Schistocytes on peripheral blood smear
Schistocytes on peripheral blood smear ×100: Up to 3 schistocytes per high-power field is normal. Arrows show more than 10 schistocytes per high-power field. | Picture taken with oil emersion lens at ×100. | Benjamin M. Boral, DO, Dennis J. Williams, MD, Leonard I. Boral, MD, MBA, Disseminated Intravascular Coagulation, American Journal of Clinical Pathology, Volume 146, Issue 6, December 2016, Pages 670–680, https://doi.org/10.1093/ajcp/aqw195

Differential diagnosis:

Differential diagnosis of DIC
Differential diagnosis of DIC | Venugopal A. (2014). Disseminated intravascular coagulation. Indian journal of anaesthesia, 58(5), 603–608. https://doi.org/10.4103/0019-5049.144666

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

Summary:

Disseminated intravascular coagulation
Disseminated intravascular coagulation. Nat Rev Dis Prim [Internet]. 2016 Jun 2;2:16038. Available from: http://dx.doi.org/10.1038/nrdp.2016.38

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