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Thromboelastometry and platelet function during acclimatization to high altitude

Thromboelastometry and platelet function during acclimatization to high altitude
Thromboelastometry and platelet function during acclimatization to high altitude

Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.

haemostasis, high altitude, hypoxia, platelet function, thromboelastometry
0340-6245
63-71
Rocke, Alistair S.
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Paterson, Gordon G.
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Barber, Matthew T.
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Jackson, Alexander I.R.
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Main, Shona
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Stannett, Calum
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Schnopp, Martin F.
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Baillie, J. Kenneth
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Horne, Elizabeth H.
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Moores, Carl
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Harrison, Paul
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Nimmo, Alastair F.
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Thompson, A. A.Roger
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Rocke, Alistair S.
f59e6a62-f52d-4c0e-8e72-3dac786ba716
Paterson, Gordon G.
0fd75637-87f3-45c0-b99d-64abac8b8dc9
Barber, Matthew T.
0372c5a5-9955-4763-8c98-0532758fb31d
Jackson, Alexander I.R.
9bbcdd0e-a9c8-46d3-945c-53e9262c4f4c
Main, Shona
a8fa05fb-dba5-4b20-8ca8-7104c58bbae6
Stannett, Calum
37b36399-660f-46ef-93f9-9c7208c6877d
Schnopp, Martin F.
cec7d26e-461b-472a-9437-5905ee407a2e
Baillie, J. Kenneth
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Horne, Elizabeth H.
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Moores, Carl
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Harrison, Paul
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Nimmo, Alastair F.
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Thompson, A. A.Roger
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Rocke, Alistair S., Paterson, Gordon G., Barber, Matthew T., Jackson, Alexander I.R., Main, Shona, Stannett, Calum, Schnopp, Martin F., Baillie, J. Kenneth, Horne, Elizabeth H., Moores, Carl, Harrison, Paul, Nimmo, Alastair F. and Thompson, A. A.Roger (2018) Thromboelastometry and platelet function during acclimatization to high altitude. Thrombosis and Haemostasis, 118 (1), 63-71. (doi:10.1160/TH17-02-0138).

Record type: Article

Abstract

Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.

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TH17-02-0138
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Accepted/In Press date: 23 September 2017
e-pub ahead of print date: 5 January 2018
Keywords: haemostasis, high altitude, hypoxia, platelet function, thromboelastometry

Identifiers

Local EPrints ID: 424464
URI: http://eprints.soton.ac.uk/id/eprint/424464
ISSN: 0340-6245
PURE UUID: c56d9dfa-1516-461b-8786-65b7934bcbd3
ORCID for Alexander I.R. Jackson: ORCID iD orcid.org/0000-0002-3153-9231

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Date deposited: 05 Oct 2018 11:37
Last modified: 07 Oct 2020 02:21

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Contributors

Author: Alistair S. Rocke
Author: Gordon G. Paterson
Author: Matthew T. Barber
Author: Alexander I.R. Jackson ORCID iD
Author: Shona Main
Author: Calum Stannett
Author: Martin F. Schnopp
Author: J. Kenneth Baillie
Author: Elizabeth H. Horne
Author: Carl Moores
Author: Paul Harrison
Author: Alastair F. Nimmo
Author: A. A.Roger Thompson

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