Platelet anaesthesia during extracorporeal circulation: differential effects of GP IIb/IIIa blockers on platelet activation marker P-selectin expression at hypothermia.
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.
Straub
Andreas
A
Department of Thoracic, Cardiac and Vascular Surgery, University of Tübingen, Germany.
Schiebold
Daniela
D
Wendel
Hans Peter
HP
Azevedo
Ruben
R
Dietz
Klaus
K
Ziemer
Gerhard
G
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
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