title: Sevoflurane inhibits unstimulated and agonist-induced platelet antigen expression and platelet function in whole blood in vitro.
abstract: BACKGROUND
  Previous studies have reported conflicting results about the effect of sevoflurane on platelet aggregation. To clarify this point, we investigated the effects of sevoflurane on platelet antigen expression and function in vitro.
  
  
  METHODS
  Human whole blood was incubated for 1 h with 0.5 and 1 minimum alveolar concentration sevoflurane, 21% O(2), and 5% CO(2). A control sample was kept at the same conditions without sevoflurane. After stimulation with adenosine diphosphate or thrombin receptor agonist peptide 6, samples were stained with fluorochrome conjugated antibodies, and the expression of platelet glycoproteins GPIIb/IIIa, GPIb, and P-selectin, as well as activated GPIIb/IIIa, were measured with two-color flow cytometry. In addition, platelet function was assessed by means of thromboelastography and using the platelet function analyzer 100.
  
  
  RESULTS
  Already in subanesthetic concentrations, sevoflurane inhibits unstimulated and agonist-induced GPIIb/IIIa surface expression and activated GPIIb/IIIa expression on platelets in whole blood. The agonist-induced redistribution of GPIb into the open canalicular system was also impaired by sevoflurane, whereas no effect on P-selectin expression in activated platelets could be found. Sevoflurane significantly reduced the maximum thromboelastographic amplitude. Furthermore, platelet function analyzer 100 closure times were significantly prolonged.
  
  
  CONCLUSIONS
  The results show that sevoflurane significantly impairs platelet antigen expression in vitro. It is especially the inhibition of GPIIb/IIIa expression and activation that impairs bleeding time as reflected in thromboelastographic measurements and platelet function analyzer 100 closure times. The exact inhibitory mechanism remains unclear.
authors.affiliation: Department of Anesthesiology, Rheinisch-Westfälische Technische Hochschule Aachen, Germany. nhorn@post.klinikum.rwth-aachen.de
authors.forename: N A
authors.initials: NA
authors.lastname: Horn
authors.forename: L
authors.initials: L
authors.lastname: de Rossi
authors.forename: T
authors.initials: T
authors.lastname: Robitzsch
authors.forename: K E
authors.initials: KE
authors.lastname: Hecker
authors.forename: G
authors.initials: G
authors.lastname: Hutschenreuter
authors.forename: R
authors.initials: R
authors.lastname: Rossaint
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008738:Methyl Ethers / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects*; D000077149:Sevoflurane; D013916:Thrombelastography
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077149:Sevoflurane