Published in:
Open Access
01-12-2018 | Research
Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin
Authors:
Takuro Arishima, Takashi Ito, Tomotsugu Yasuda, Nozomi Yashima, Hiroaki Furubeppu, Chinatsu Kamikokuryo, Takahiro Futatsuki, Yutaro Madokoro, Shotaro Miyamoto, Tomohiro Eguchi, Hiroyuki Haraura, Ikuro Maruyama, Yasuyuki Kakihana
Published in:
Thrombosis Journal
|
Issue 1/2018
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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.