Hypothermia-Induced Platelet Aggregation: No Effect of Aprotinin (Trasylol®) but Inhibition by Eptifibatide (Integrilin®)[*]

Abstract

Objectives: The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversial, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has been assumed to preserve platelet function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet function under conditions of DHCA. Methods: Heparinized blood from healthy volunteers (n = 10) was incubated in stasis for 30 minutes at 18 °C to simulate DHCA and compared to samples incubated at 37 °C. The effect of eptifibatide (2.5 µg/ml) and aprotinin (300 KIU/ml) on platelets under these conditions was analyzed by flow cytometry. Platelet aggregates were identified using CD41-antibody binding and size. GPIIb/IIIa function was evaluated with the activation-specific antibody PAC-1 after stimulation with 10 µM ADP. Aggregate numbers and antibody mean-fluorescence are reported as mean ± standard deviation. Results: Hypothermia induced a 2.5-fold increase of aggregates (p < 0.001) and a 2.6-fold increase of GPIIb/IIIa activation (p < 0.001). This effect was not influenced by aprotinin but almost completely inhibited by eptifibatide (p < 0.001). Conclusions: Aprotinin has no procoagulatory effect on platelet function during hypothermia but is not protective either. Eptifibatide inhibits hypothermia-induced platelet aggregation in vitro and may prevent aggregate sequestration in the microvasculature and consecutive ischemic organ damage in vivo.

Key words

Hypothermia - platelets - aprotinin - GP IIb/IIIa inhibition

1 This work has been presented at the 4th joint meeting of the German, Austrian, and Swiss Society for Thoracic and Cardiovascular Surgery (Hamburg 17. 2. 2004, session Nr. 39). The work was supported by the Medical Faculty of the University of Tübingen (Fortüne-program)

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1 This work has been presented at the 4th joint meeting of the German, Austrian, and Swiss Society for Thoracic and Cardiovascular Surgery (Hamburg 17. 2. 2004, session Nr. 39). The work was supported by the Medical Faculty of the University of Tübingen (Fortüne-program)