Abstract
While recombinant thrombomodulin's (rTM) effect on blood clotting are known, its effect on platelets is not clear. This study investigated the effect of rTM (ART 123, Asahi Pharmaceutical, Japan) on platelets using platelet aggregation, release and activation assays. In platelet aggregation studies, citrated whole blood was supplemented with 0–10 μg/ml rTM. Aggregation was induced by ADP (5 and 2.5 μM) or thrombin (0.5 U/ml). Platelet activation was measured by flow cytometry following stimulation with rTF or ADP. Platelet release was measured as 14C serotonin release (SRA) from washed platelets. In platelet aggregation assays, rTM did not inhibit ADP‐induced aggregation, but concentration‐dependently inhibited thrombin induced aggregation (IC50: 0.42 μg/ml). rTM enhanced microparticle generation at low concentrations, but at concentrations > 0.31 μg/ml rTM concentration dependently inhibited microparticle formation (IC50: 2.5 μg/ml). At concentrations >5.0 μg/ml, rTM completely blocked TF‐induced microparticle formation, but did not block P‐selectin expression. rTM inhibited thrombin‐induced serotonin release. These studies suggest that while rTM does not inhibit agonist induced platelet aggregation, it can inhibit TF induced microparticle formation. As rTM concentrations up to 10 μg/ml do not affect P‐selectin expression, it is unlikely to alter primary hemostasis at therapeutic levels.
Published Version
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