Thrombomodulin has a pivotal role in the
protein C system that is important in the pathogenesis of
sepsis. In
sepsis, endothelial cell expression of
thrombomodulin is strongly downregulated, causing an impaired activation of
protein C that is central in the modulation of coagulation activation and inflammatory processes. In addition,
thrombomodulin itself has marked immunomodulatory effects, targeting neutrophil adhesion, complement activation and
cytokine generation. Several preclinical studies in experimental
sepsis models have shown that administration of soluble
thrombomodulin is capable of improving the derangement of coagulation, ameliorates inflammatory responses and may restore organ dysfunction. Initial clinical studies in patients with
disseminated intravascular coagulation, of whom a significant proportion were patients with
sepsis, demonstrate a beneficial effect of recombinant soluble
thrombomodulin on restoration of coagulation and improvement of organ failure.