TY - JOUR
T1 - Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin
AU - Arishima, Takuro
AU - Ito, Takashi
AU - Yasuda, Tomotsugu
AU - Yashima, Nozomi
AU - Furubeppu, Hiroaki
AU - Kamikokuryo, Chinatsu
AU - Futatsuki, Takahiro
AU - Madokoro, Yutaro
AU - Miyamoto, Shotaro
AU - Eguchi, Tomohiro
AU - Haraura, Hiroyuki
AU - Maruyama, Ikuro
AU - Kakihana, Yasuyuki
N1 - Funding Information:
This study was supported by Asahi Kasei Pharma.
Funding Information:
IM and TI have received research funding from Asahi Kasei Pharma, outside of the submitted work. All other authors state that they have no conflict of interests.
PY - 2018/9/28
Y1 - 2018/9/28
N2 - 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.
AB - 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.
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U2 - 10.1186/s12959-018-0178-0
DO - 10.1186/s12959-018-0178-0
M3 - Article
AN - SCOPUS:85054256923
VL - 16
JO - Thrombosis Journal
JF - Thrombosis Journal
SN - 1477-9560
IS - 1
M1 - 24
ER -