title: The effect of sibutramine, a serotonin-norepinephrine reuptake inhibitor, on platelets and fibrin networks of male Sprague-Dawley rats: a descriptive study.
abstract: Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.
authors.affiliation: Department of Anatomy and.
authors.forename: Ciska
authors.initials: C
authors.lastname: van der Schoor
authors.forename: Hester Magdalena
authors.initials: HM
authors.lastname: Oberholzer
authors.forename: Megan Jean
authors.initials: MJ
authors.lastname: Bester
authors.forename: Mia-Jeanne
authors.initials: MJ
authors.lastname: van Rooy
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D003503:Cyclobutanes / Q000633:toxicity*; D005337:Fibrin / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; D005337:Fibrin; C058254:sibutramine
keywords: Fibrin networks; plasma; platelets; prothrombotic state; sibutramine