Key result
Thrombomodulin inhibited thrombin generation by >50% when activated protein C levels increased by >/ml in plasma from patients with disseminated intravascular coagulation.
Why the study?
Does thrombomodulin inhibit thrombin generation and accelerate activated protein C production in plasma from DIC patients?
Does thrombomodulin inhibit thrombin generation and accelerate activated protein C production in plasma from DIC patients?
Thrombomodulin effectively inhibits thrombin generation in DIC patient plasma by accelerating APC production, suggesting the thrombin generation test could be used to predict individual patient efficacy prior to administration.
Answers are grounded in this paper and cite their sources.
Supports thrombin generation testing to predict thrombomodulin response in DIC; hypothesis-generating, should not yet change practice.
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 μg/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.
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Wada et al. (2005) studied Disseminated intravascular coagulation (DIC). Thrombomodulin was evaluated on Thrombin generation and activated protein C production. Thrombomodulin inhibited thrombin generation by >50% when activated protein C levels increased by >/ml in plasma from patients with disseminated intravascular coagulation.
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