M. Levi et al., Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation, CRIT CARE M, 29(7), 2001, pp. S90-S94
Objective: In the pathogenesis of disseminated intravascular coagulation, d
ysfunctional natural anticoagulant pathways appear to play a pivotal role.
In this article, we will address the mechanisms that contribute to this def
ect in the regulation of coagulation activation. Furthermore, we will explo
re the experimental and clinical evidence that restoration of these anticoa
gulant pathways results in clinical improvement.
Data Sources:We have searched and reviewed published articles on experiment
al studies of disseminated intravascular coagulation models in animals and
clinical studies in patients with disseminated intravascular coagulation.
Data Synthesis: All three major anticoagulant pathways, that is, the antith
rombin pathway, the protein C system, and tissue factor pathway inhibitor,
are defective in sepsis and disseminated intravascular coagulation. Several
mechanisms contribute to this defect. Restoration of these pathways, in pr
inciple, by administration of coagulation inhibitor concentrates or recombi
nant anticoagulant factors, appears to ameliorate the coagulation disorder
and, more important, result in improvement of clinically relevant outcomes,
such as a reduction of organ failure and mortality.
Conclusions: Restoration of disrupted physiologic anticoagulant pathways in
disseminated intravascular coagulation is not only a logical paint of impa
ct in patients with sepsis and an activated coagulation system, but also is
associated with an improved outcome in experimental and (initial) clinical
studies.