title: Platelet anaesthesia during extracorporeal circulation: differential effects of GP IIb/IIIa blockers on platelet activation marker P-selectin expression at hypothermia.
abstract: BACKGROUND
  Blood contact with artificial surfaces of extracorporeal circulation (ECC) and hypothermia as applied in cardiac surgery cause platelet dysfunction possibly followed by bleeding complications. "Platelet anaesthesia" is a pharmacological strategy to protect platelets against ECC-induced damage using a GP IIb/IIIa blocker, which should be short acting to achieve maximal therapy control thereby avoiding post-ECC haemorrhage. However, GP IIb/IIIa blockers can paradoxically induce platelet activation, which may limit their efficiency as anti-platelet drugs. This in-vitro study investigated potentially platelet-activating effects of short-acting GP IIb/IIIa blockers during normothermic and hypothermic ECC.
  
  
  METHODS
  Control (untreated) and treated (using either FK633 [half-life: 0.52 h], tirofiban [half-life: 1.5-2 h], or eptifibatide [half-life: 1.5 h]) heparinized blood was circulated in an ECC-model at normothermia (37 degrees C) and hypothermia (18 degrees C). Percentages of platelet aggregates and P-selectin-expressing (activated) platelets, platelet-counts and Thrombin-Antithrombin (TAT) complex formation were determined before (baseline) and after ECC. Statistical analysis was performed using multifactorial ANOVA after log-transforming the data.
  
  
  RESULTS
  GP IIb/IIIa blockade inhibited ECC-induced platelet aggregation and platelet loss and decreased P-selectin expression at normothermia. During hypothermic ECC P-selectin was decreased by tirofiban but augmented by FK633 and eptifibatide. TAT formation was only decreased by FK633.
  
  
  CONCLUSIONS
  Especially regarding its ultra-short half-life FK633 has the best properties for platelet protection during normothermic ECC. However, at hypothermia FK633 and eptifibatide induce platelet activation. In relation with "platelet anaesthesia" possible hypothermia-associated prothrombotic side effects of GP IIb/IIIa blockers should be considered.
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University of Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Straub
authors.forename: Daniela
authors.initials: D
authors.lastname: Schiebold
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Wendel
authors.forename: Ruben
authors.initials: R
authors.lastname: Azevedo
authors.forename: Klaus
authors.initials: K
authors.lastname: Dietz
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ziemer
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000990:Antithrombin III / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology*; D005112:Extracorporeal Circulation; D005434:Flow Cytometry; D006801:Humans; D007036:Hypothermia, Induced; D008297:Male; D019007:P-Selectin / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013696:Temperature
chemical_list: D004151:Dipeptides; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C046193:antithrombin III-protease complex; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D000244:Adenosine Diphosphate; D000990:Antithrombin III; D010447:Peptide Hydrolases