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2016 ; 36
(6
): 505-12
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Current Pathological and Laboratory Considerations in the Diagnosis of
Disseminated Intravascular Coagulation
#MMPMID27578502
Toh CH
; Alhamdi Y
; Abrams ST
Ann Lab Med
2016[Nov]; 36
(6
): 505-12
PMID27578502
show ga
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.