Review Article

Ann Lab Med 2016; 36(6): 505-512

Published online November 1, 2016

Copyright © Korean Society for Laboratory Medicine.

Current Pathological and Laboratory Considerations in the Diagnosis of Disseminated Intravascular Coagulation

Cheng-Hock Toh, M.D.1,2, Yasir Alhamdi, Ph.D.1, and Simon T. Abrams, Ph.D.1

Institute of Infection and Global Health1, University of Liverpool, Liverpool; Roald Dahl Haemostasis & Thrombosis Centre2, Royal Liverpool University Hospital, Liverpool, United Kingdom

Correspondence to: Cheng-Hock Toh
Roald Dahl Haemostasis & Thrombosis Centre, Royal Liverpool University Hospital, Liverpool, L7 8XP, United Kingdom
Tel: +44-(0)151-795-9637
Fax: +44-(0)151-706-5810

Received: May 4, 2016; Revised: June 21, 2016; Accepted: July 22, 2016


Systemically sustained thrombin generation in vivo is the hallmark of disseminated intravascular coagulation (DIC). Typically, this is in response to a progressing disease state that is associated with significant cellular injury. The etiology could be infectious or noninfectious, with the main pathophysiological mechanisms involving cross-activation among coagulation, innate immunity, and inflammatory responses. This leads to consumption of both pro- and anticoagulant factors as well as endothelial dysfunction and disrupted homeostasis at the blood vessel wall interface. In addition to the release of tissue plasminogen activator (tPA) and soluble thrombomodulin (sTM) following cellular activation and damage, respectively, there is the release of damage-associated molecular patterns (DAMPs) such as extracellular histones and cell-free DNA. Extracellular histones are increasingly recognized as significantly pathogenic in critical illnesses through direct cell toxicity, the promotion of thrombin generation, and the induction of neutrophil extracellular trap (NET) formation. Clinically, high circulating levels of histones and histone?DNA complexes are associated with multiorgan failure, DIC, and adverse patient outcomes. Their measurements as well as that of other DAMPs and molecular markers of thrombin generation are not yet applicable in the routine diagnostic laboratory. To provide a practical diagnostic tool for acute DIC, a composite scoring system using rapidly available coagulation tests is recommended by the International Society on Thrombosis and Haemostasis. Its usefulness and limitations are discussed alongside the advances and unanswered questions in DIC pathogenesis.

Keywords: Disseminated intravascular coagulation, Damage-associated molecular patterns, Molecular markers