title: Thrombomodulin accelerates activated protein C production and inhibits thrombin generation in the plasma of disseminated intravascular coagulation patients.
abstract: Thrombomodulin (TM) has been under development as a medicine for disseminated intravascular coagulation (DIC), and is expected to exhibit strong anticoagulant activity by inhibiting thrombin generation via the acceleration of protein C activation. In the present study, we examined the pharmacological action of TM in plasma obtained from DIC patients. TM was found to inhibit thrombin generation and accelerate activated protein C (APC) production at 0.3-30 TM units/ml in plasma obtained from DIC patients irrespective of their underlying disorders. In addition, there was a positive correlation between the inhibition of thrombin generation and the amount of APC produced. Thrombin generation was inhibited by over 50% when the plasma level of APC was increased by more than 0.2 microg/ml. These results indicate that TM inhibits thrombin generation in plasma obtained from DIC patients by accelerating APC production. Moreover, the results imply that the thrombin generation test may be a good method to speculate the efficacy of TM on every patient before the administration of TM.
authors.affiliation: Department of Laboratory Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. wadahide@clin.medic.mie-u.ac.jp
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Miho
authors.initials: M
authors.lastname: Sakakura
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kushiya
authors.forename: Masakatu
authors.initials: M
authors.lastname: Nisikawa
authors.forename: Katsuya
authors.initials: K
authors.lastname: Onishi
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiku
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
mesh_terms: D004211:Disseminated Intravascular Coagulation / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D011486:Protein C / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism*
chemical_list: D011486:Protein C; D018180:Thrombomodulin; D013917:Thrombin