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Thromb Haemost 2018; 118(05): 883-892
DOI: 10.1055/s-0038-1641566
Cellular Haemostasis and Platelets
Schattauer GmbH Stuttgart

Hypobaric Hypoxia Causes Elevated Thrombin Generation Mediated by FVIII that is Balanced by Decreased Platelet Activation

Cécile H. Kicken
1   Department of Anaesthesiology, Maastricht University Medical Centre, Maastricht, The Netherlands
2   Synapse Research Institute, Maastricht, The Netherlands
,
Marisa Ninivaggi
2   Synapse Research Institute, Maastricht, The Netherlands
,
Joke Konings
2   Synapse Research Institute, Maastricht, The Netherlands
,
Martijn Moorlag
3   Department of Biochemistry, Maastricht University, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
,
Dana Huskens
2   Synapse Research Institute, Maastricht, The Netherlands
,
Jasper A. Remijn
2   Synapse Research Institute, Maastricht, The Netherlands
4   Department of Clinical Chemistry and Haematology, Gelre Hospitals, Apeldoorn, The Netherlands
,
Saartje Bloemen
3   Department of Biochemistry, Maastricht University, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
,
Marcus D. Lancé
5   Department of Anaesthesiology, Intensive Care and Perioperative Medicine, Hamad Medical Centre, Doha, Qatar
,
Bas De Laat
2   Synapse Research Institute, Maastricht, The Netherlands
3   Department of Biochemistry, Maastricht University, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands
› Author Affiliations Funding This work was supported by departmental funds from Synapse Research Institute.
Further Information

Publication History

06 December 2017

02 March 2018

Publication Date:
03 April 2018 (online)

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Abstract

Introduction Epidemiological studies suggest that hypobaric hypoxia at high altitude poses a risk for developing venous thromboembolism. The cause of this observed hypercoagulability remains unclear. Therefore, this study aimed to investigate the effect of hypobaric hypoxia at 3,883 m above sea level on thrombin generation and platelet activation.

Methods After complying with medical ethical procedures, 18 participants were recruited, of whom 1 had to leave the study prematurely due to mild acute mountain sickness. Blood was drawn first at 50 m above sea level and second at 3,883 m altitude after gradual acclimatization for 6 days. Thrombin generation was measured in whole blood, platelet-rich plasma and platelet-poor plasma. Platelet activation was assessed using a whole blood flow-cytometric assay. Coagulation factor levels, D-dimer levels and markers of dehydration and inflammation were measured.

Results Hypobaric hypoxia at 3,883 m altitude caused increased thrombin generation, measured as peak height and endogenous thrombin potential, in whole blood, platelet-rich and platelet-poor plasma without or at low tissue factor concentration. The elevated thrombin generation was mediated by increased factor VIII levels and not caused by dehydration or inflammation. In contrast, spontaneous and agonist-induced platelet activation was decreased at high altitude.

Conclusion Hypobaric hypoxia causes increased factor VIII-mediated thrombin generation. The hypercoagulability was balanced by decreased platelet activation. These findings may explain why venous, and not arterial thrombotic events occur more frequently at high altitude.

Keywords

hypoxia - thrombin generation - platelet activation

Supplementary Material

 

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