Platelet anaesthesia during extracorporeal circulation: Differential effects of GP IIb/IIIa blockers on platelet activation marker P-selectin expression at hypothermia

• Published in: Thrombosis research 2008, Vol.122 (3), p.383-389
• Main Authors: Straub, Andreas, Schiebold, Daniela, Wendel, Hans Peter, Azevedo, Ruben, Dietz, Klaus, Ziemer, Gerhard
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Antithrombin III - metabolism; Blood Platelets - drug effects; Blood Platelets - physiology; Dipeptides - pharmacology; Extracorporeal Circulation; Flow Cytometry; GP IIb/IIIa blockade; Hematology, Oncology and Palliative Medicine; Humans; Hypothermia, Induced; Male; P-Selectin - metabolism; Peptide Hydrolases - metabolism; Platelet Activation - drug effects; Platelet Activation - physiology; Platelet Count; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Platelets; Temperature
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2008.01.001

Abstract Introduction 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. Materials and 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 °C) and hypothermia (18 °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.