Thrombomodulin alfa prevents the decrease in platelet aggregation in rat models of disseminated intravascular coagulation.


Laboratory for Pharmacology, Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, Shizuoka, Japan. Electronic address: [Email]


BACKGROUND : Disseminated intravascular coagulation (DIC), a deadly complication characterized by uncontrolled hypercoagulation, causes a decrease in the platelet count and impairs platelet aggregation. Thrombomodulin (TM) alfa, a recombinant human soluble TM, reduces hypercoagulation in DIC patients. However, the effects of TM alfa on impaired platelet aggregation remain to be determined. In this study, we aim to investigate the effects of TM alfa on platelet aggregation using lipopolysaccharide (LPS)-induced and tissue factor (TF)-induced DIC rat models.
METHODS : Sprague-Dawley rats were administered TF or LPS intravenously, with or without TM alfa before the injection. Six hours after LPS injection or 1 h after TF infusion, blood samples were obtained, and platelet-rich plasma was prepared. Collagen or adenosine diphosphate-induced platelet aggregation was measured using an aggregometer. In the other experiments, platelets were transfused 1 h after the TF infusion. Five minutes after transfusion, collagen-induced platelet aggregation was also measured.
RESULTS : The amplitude of platelet aggregation in platelet-rich plasma was decreased in LPS- and TF-treated rats. TM alfa inhibited the decrease in platelet aggregation in a dose-dependent manner. The washed platelet aggregation amplitude was not decreased in TF-treated rats. Suspension of normal platelets in plasma obtained from TF-treated rats reduced platelet aggregation. Platelet transfusion for TF-treated rats increased the platelet count but was unable to improve platelet aggregation.
CONCLUSIONS : TM alfa attenuated impairment of platelet aggregation in LPS- and TF-induced DIC rat models. The changes in plasma composition played a role in the decrease of platelet aggregation in TF-treated rats.


Disseminated intravascular coagulation,Platelet aggregation,Platelet transfusion,Thrombomodulin,Thromboplastin,