CC BY 4.0 · TH Open 2019; 03(03): e216-e226
DOI: 10.1055/s-0039-1692991
Original Article
Georg Thieme Verlag KG Stuttgart · New York

A Hypoxic Environment Attenuates Exercise-Induced Procoagulant Changes Due to Decreased Platelet Activation

1   Department of Anesthesiology, Maastricht University Medical Center, Maastricht, The Netherlands
2   Synapse Research Institute, Maastricht, The Netherlands
,
Lisa N. van der Vorm
2   Synapse Research Institute, Maastricht, The Netherlands
3   Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands
4   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Suzanne Zwaveling
2   Synapse Research Institute, Maastricht, The Netherlands
4   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Evi Schoenmaker
2   Synapse Research Institute, Maastricht, The Netherlands
,
Jasper A. Remijn
3   Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands
4   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
5   Department of Clinical Chemistry, Meander Medical Center, Amersfoort, The Netherlands
,
Dana Huskens
2   Synapse Research Institute, Maastricht, The Netherlands
,
Bas de Laat
2   Synapse Research Institute, Maastricht, The Netherlands
4   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

11 March 2019

23 May 2019

Publication Date:
22 July 2019 (online)

Abstract

Introduction Although physical exercise is protective against cardiovascular disease, it can also provoke sudden cardiac death (exercise paradox). Epidemiological studies suggest that systemic hypoxia at high altitude is a risk factor for venous thromboembolism. Forthcoming, this study investigated the effect of repeated exercise at high altitude on blood coagulation, platelet function, and fibrinolysis.

Methods Six trained male volunteers were recruited. Participants ascended from sea level to 3,375 m altitude. They performed four exercise tests at 65 to 80% of their heart-rate reserve during 2 hours: one time at sea level and three times on consecutive days at 3,375 m altitude. Thrombin generation (TG) was measured in whole blood (WB) and platelet-rich and platelet-poor plasma. Coagulation factor levels were measured. Platelet activation was measured as αIIbβ3 activation and P-selectin expression. Fibrinolysis was studied using a clot-lysis assay.

Results Normoxic exercise increased plasma peak TG through increased factor VIII (FVIII), and increased von Willebrand factor (VWF) and active VWF levels. Platelet granule release potential was slightly decreased. After repetitive hypoxic exercise, the increase in (active) VWF tapered, and there was no more distinct exercise-related increase in peak. Platelet aggregation potential and platelet-dependent TG decreased at high altitude. There were no effects on fibrinolysis upon exercise and/or hypoxia.

Conclusion Strenuous exercise induces a procoagulant state that is mediated by the endothelium, by increasing VWF and secondarily raising FVIII levels. After repetitive exercise, the amplitude of the endothelial response to exercise diminishes. A hypoxic environment appears to further attenuate the procoagulant changes by decreasing platelet activation and platelet-dependent TG.

Authors' Contributions

C.K. and B.L. designed the study protocol and obtained approval of the medical ethical research committee. C.K., B.L., and S.Z. were responsible for participant recruitment, informed consent, medical assessment and inclusion. C.K., S.Z., E.S., L.V., J.R., and D.H. performed experiments. C.K., S.Z., and D.H. analyzed the data. C.K. and L.V. wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.


Supplementary Material

 
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