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Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment

Högberg, Carl LU ; Erlinge, David LU orcid and Braun, Oscar O LU (2009) In Thrombosis Journal 7.
Abstract

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... (More)

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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type
Contribution to journal
publication status
published
subject
in
Thrombosis Journal
volume
7
article number
2
publisher
BioMed Central (BMC)
external identifiers
  • pmid:19236702
  • scopus:62149135942
ISSN
1477-9560
DOI
10.1186/1477-9560-7-2
language
English
LU publication?
yes
id
93e7ae72-305b-4a3e-a7d4-70efff494a00
date added to LUP
2019-06-18 22:38:28
date last changed
2024-01-16 02:34:29
@article{93e7ae72-305b-4a3e-a7d4-70efff494a00,
  abstract     = {{<p>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.</p><p>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.</p><p>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 &lt; 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.</p><p>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.</p>}},
  author       = {{Högberg, Carl and Erlinge, David and Braun, Oscar O}},
  issn         = {{1477-9560}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Thrombosis Journal}},
  title        = {{Mild hypothermia does not attenuate platelet aggregation and may even increase ADP-stimulated platelet aggregation after clopidogrel treatment}},
  url          = {{http://dx.doi.org/10.1186/1477-9560-7-2}},
  doi          = {{10.1186/1477-9560-7-2}},
  volume       = {{7}},
  year         = {{2009}},
}