Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation.
OBJECTIVE
In the pathogenesis of disseminated intravascular coagulation, dysfunctional natural anticoagulant pathways appear to play a pivotal role. In this article, we will address the mechanisms that contribute to this defect in the regulation of coagulation activation. Furthermore, we will explore the experimental and clinical evidence that restoration of these anticoagulant pathways results in clinical improvement.


METHODS
We have searched and reviewed published articles on experimental studies of disseminated intravascular coagulation models in animals and clinical studies in patients with disseminated intravascular coagulation.


RESULTS
All three major anticoagulant pathways, that is, the antithrombin 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 principle, by administration of coagulation inhibitor concentrates or recombinant 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 point of impact in patients with sepsis and an activated coagulation system, but also is associated with an improved outcome in experimental and (initial) clinical studies.
Levi
M
M
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
de Jonge
E
E
van der Poll
T
T
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D006801:Humans; D009102:Multiple Organ Failure / Q000382:microbiology; D011486:Protein C / Q000187:drug effects / Q000502:physiology / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013917:Thrombin / Q000187:drug effects / Q000502:physiology; D013925:Thromboplastin / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D000925:Anticoagulants; D016207:Cytokines; D011486:Protein C; D013925:Thromboplastin; D013917:Thrombin