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Updated: Jun 25, 2026
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation
Carl Högberg1, David Erlinge, Oscar O Braun
1Department of Cardiology, Lund University, Lund, Sweden. carl.hogberg@med.lu.se
Insights
Mild hypothermia did not reduce platelet aggregation and actually increased it after clopidogrel treatment. This suggests dual antiplatelet therapy may be necessary for patients undergoing mild hypothermia.
Area of Science:
- Cardiovascular Research
- Hematology
- Pharmacology
Background:
- Mild hypothermia is a standard treatment for cardiac arrest patients.
- A common assumption is that hypothermia reduces platelet aggregation.
- The effect of clopidogrel on platelet aggregation during hypothermia requires investigation.
Purpose of the Study:
- To investigate the impact of mild hypothermia on platelet aggregation.
- To determine how clopidogrel affects platelet aggregation under hypothermic conditions.
Main Methods:
- Evaluated platelet reactivity at 37°C and 33°C using light transmission aggregometry and VASP.
- Assessed blood from healthy volunteers before and after a 600 mg clopidogrel loading dose.
- Utilized various agonists including ADP, collagen, and U46619.
Main Results:
- Hypothermia did not attenuate, and sometimes increased, platelet aggregation induced by various agonists.
- ADP-induced platelet aggregation was significantly higher at 33°C compared to 37°C after clopidogrel administration.
- Reduced responsiveness to clopidogrel during hypothermia could be reversed by a P2Y12 antagonist.
Conclusions:
- Mild hypothermia does not inhibit platelet aggregation and can enhance ADP-stimulated aggregation post-clopidogrel.
- Dual antiplatelet therapy (aspirin and a P2Y12 antagonist) is likely necessary for patients on mild hypothermia.
- Future ADP blockers might offer benefits in this patient population.
Background:
Mild hypothermia is currently standard of care for cardiac arrest patients in many hospitals and a common belief is that hypothermia attenuates platelet aggregation. We wanted to examine the effects of clopidogrel on platelet aggregation during hypothermia.
Methods:
Platelet reactivity at 37° C and 33° C was evaluated by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) in blood from healthy volunteers before, and 24 hours after, a 600 mg loading dose of clopidogrel.
Results:
Collagen, 5-HT, epinephrine, U46619 and ADP-induced platelet aggregation was unaltered or even increased by hypothermia. After clopidogrel, there was a significant increase in platelet aggregation for 5 and 20 muM ADP at 33° C compared to 37° C (46 ± 5 vs. 34 ± 5% and 58 ± 4 vs. 47 ± 4%, p < 0.001, n = 8). Hypothermia also increased ADP-induced aggregation after pretreatment with the P2Y1 antagonist MRS2500. The decreased responsiveness to clopidogrel during hypothermia could be overcome by addition of the reversible P2Y12 antagonist AZD6140. ADP-induced inhibition of VASP-phosphorylation was unaffected by hypothermia both in the presence and absence of clopidogrel. A dose-response curve for ADP-induced platelet aggregation revealed increased potency for ADP during hypothermia with no difference in efficacy.
Conclusion:
Mild hypothermia did not attenuate platelet aggregation, instead it even increased ADP-stimulated platelet aggregation after clopidogrel treatment. Dual platelet inhibition with aspirin and a P2Y12 receptor antagonist is probably needed for patients with acute coronary syndromes treated with mild hypothermia, and it is possible that future ADP blockers could be of benefit.
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