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Takuro Arishima¹, Takashi Ito^1,2, Tomotsugu Yasuda¹

¹1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan.

Thrombosis Journal

|October 3, 2018

Abstract

Background:

Recombinant human soluble thrombomodulin (rTM) has been used for the treatment of disseminated intravascular coagulation in Japan, and an international phase III clinical trial for rTM is currently in progress. rTM mainly exerts its anticoagulant effects through an activated protein C (APC)-dependent mechanism, but the circulating APC levels after rTM treatment have not been clarified. This prospective observational study investigated plasma APC levels after rTM treatment.

Methods:

Plasma levels of soluble thrombomodulin, thrombin-antithrombin complex (TAT), protein C, and APC were measured in eight septic patients treated with rTM. APC generation in vitro was assessed in the presence or absence of rTM.

Results:

rTM significantly increased thrombin-mediated APC generation in vitro. In septic patients, soluble thrombomodulin levels were significantly increased during a 30-60-min period of rTM treatment and TAT levels were decreased. However, APC activity was not increased during the treatment period.

Conclusions:

Plasma APC activity is not increased in septic patients treated with rTM. It is possible that APC acts locally and does not circulate systemically.

Keywords:

Disseminated intravascular coagulation Protein C Sepsis Thrombomodulin

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