Effects of the 5-Hydroxytryptamine 3 Receptor Antagonist Palonosetron on Hemostasis: An In Vitro Study Using Thromboelastography

<i>Background and Objectives</i>: Serotonin modulates platelet aggregation and secretion, but its role in hemostasis remains controversial. This study hypothesized that the 5-HT₃ receptor antagonist palonosetron may inhibit platelet function and aimed to evaluate its effects on blood coagulation using thromboelastography (TEG). <i>Materials and Methods</i>: Blood samples from 11 healthy volunteers were treated with palonosetron at concentrations of 25, 250, and 2500 ng/mL. Untreated samples served as controls. Coagulation parameters were assessed using global hemostasis (citrated kaolin, citrated rapid TEG, citrated kaolin with heparinase, and citrated functional fibrinogen) and PlateletMapping (adenosine diphosphate [ADP], arachidonic acid, and others) assays. <i>Results</i>: In the global hemostasis assay, maximum amplitude values, reflecting clot strength, decreased with increasing palonosetron concentrations in all tests, including citrated kaolin (<i>p</i> = 0.031), citrated rapid TEG (<i>p</i> = 0.001), citrated kaolin with heparinase (<i>p</i> = 0.033), and citrated functional fibrinogen (<i>p</i> = 0.011). The PlateletMapping assay showed significant reductions in ADP-induced platelet aggregation (<i>p</i> = 0.001), with the largest inhibition observed at 2500 ng/mL (<i>p</i> = 0.007). Despite these changes, all values remained within normal reference ranges. <i>Conclusions</i>: Palonosetron induces hypocoagulable trends in vitro by inhibiting platelet function and fibrinogen-mediated clot strength. However, these changes are unlikely to result in clinically significant hemostatic impairment when used within therapeutic doses. Further research is warranted to confirm these findings and explore their clinical relevance.