Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin.

Autor: Arishima T; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Ito T; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan.; 2Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544 Japan., Yasuda T; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Yashima N; 3Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Furubeppu H; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Kamikokuryo C; 3Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan., Futatsuki T; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Madokoro Y; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Miyamoto S; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Eguchi T; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Haraura H; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan., Maruyama I; 2Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544 Japan., Kakihana Y; 1Emergency and Critical Care Center, Kagoshima University Hospital, Kagoshima, Japan.; 3Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Jazyk: angličtina
Zdroj: Thrombosis journal [Thromb J] 2018 Sep 28; Vol. 16, pp. 24. Date of Electronic Publication: 2018 Sep 28 (Print Publication: 2018).
DOI: 10.1186/s12959-018-0178-0
Abstrakt: 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.
Competing Interests: This study was approved by the Ethics Committee of Kagoshima University Hospital. Written informed consent was obtained from all patients prior to participation in the study.Not applicable.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.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Databáze: MEDLINE
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