In
disseminated intravascular coagulation (
DIC) there is extensive crosstalk between activation of
inflammation and coagulation. Endogenous anticoagulatory pathways are downregulated by
inflammation, thus decreasing the natural anti-inflammatory mechanisms that these pathways possess. Supportive strategies aimed at inhibiting activation of coagulation and
inflammation may theoretically be justified and have been found to be beneficial in experimental and initial clinical studies. This review assembles the available experimental and clinical data on biological mechanisms of
antithrombin in inflammatory coagulation activation. Preclinical research has demonstrated partial interference of
heparin--administered even at low doses--with the
therapeutic effects of
antithrombin, and has confirmed--at the level of cellular mechanisms--a regulatory role for
antithrombin in
DIC. Against this biological background, re-analyses of data from randomized controlled trials of
antithrombin in
sepsis suggest that
antithrombin has the potential to be developed further as a therapeutic agent in the treatment of
DIC. Even though there is a lack of studies employing satisfactory methodology, the results of investigations conducted thus far into the mechanisms of action of
antithrombin allow one to infer that there is biological plausibility in the value of this agent. Final assessment of the drug's effectiveness, however, must await the availability of positive, prospective, randomized and placebo-controlled studies.