Temperature effects on haemostasis in whole blood from ticagrelor- and aspirin-treated patients with acute coronary syndrome

Abstract

Background. Comatose survivors after cardiac arrest are treated with mild induced hypothermia and potent platelet- inhibiting drugs after coronary stenting. Previous studies have shown an increased incidence of stent thrombosis during clopidogrel and aspirin treatment in conjunction with induced hypothermia. The aim of this study was to investigate the in vitro effect of induced hypo- and hyperthermia on blood from patients undergoing ticagrelor- and aspirin-mediated platelet inhibition. Methods. Whole blood from 15 patients with acute coronary syndrome who were treated with ticagrelor and aspirin and from eight healthy volunteers was incubated for 1 hour at 28, 33, 37, and 39°C. Results. In blood from patients with acute coronary syndrome, the activated clotting time (Sonoclot) was prolonged in mild hypothermic (33°C) compared to normothermic (37°C) samples. Sonoclot, clotting rate and platelet function were decreased in hypothermic compared to normothermic samples. Platelet-induced activation and aggregation (Multiplate^®) was unchanged in mild hypothermic compared to normothermic samples. In contrast, mild hypothermia supported increased platelet activation as measured with flow cytometry with up-regulation of PAC-1 and P-selectin on the platelet surface. Conclusion. In acute coronary syndrome patients treated with ticagrelor and aspirin, in vitro hypothermia to 33°C markedly increased platelet activity measured with flow cytometry, whereas viscoelastic coagulation test (Sonoclot) revealed a hypocoagulative response. Prospective clinical trials studying platelet inhibition at different temperatures and correlating changes in platelet function to bleeding or stent occlusion are needed.

Key Words::

• Induced hypothermia
• platelet aggregation
• platelet function tests
• blood coagulation
• antiplatelet drugs
• flow cytometry

Acknowledgements

We would like to thank laboratory researcher Birgitta Gullstrand for the invaluable tutorial during the laboratory work and flow cytometry analysis.

Funding

No commercial support. Lund University, ISEX-ALF Fund (Ulf Schött).

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Appendix.