Hypoxia induces a prothrombotic state independently of the physical activity

Marisa Ninivaggi, Marieke De Laat, Marcus M.D. Lancé, Cécile H. Kicken, Leonie Pelkmans, Saartje Bloemen, Marlou L. Dirks, Luc J.C. Van Loon, José W.P. Govers-Riemslag, Theo Lindhout, Joke Konings, Bas De Laat

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


Hypoxia (oxygen deprivation) is known to be associated with deep vein thrombosis and venous thromboembolism. We attempted to get a better comprehension of its mechanism by going to high altitude, thereby including the potential contributing role of physical activity. Two groups of 15 healthy individuals were exposed to hypoxia by going to an altitude of 3900 meters, either by climbing actively (active group) or transported passively by cable car (passive group). Both groups were tested for plasma fibrinogen, von Willebrand factor and factor VIII levels, fibrinolysis, thrombin generating capacity, heart rate, oxygen saturation levels and blood pressure. As a control for the passive group, 7 healthy volunteers stayed immobile in bed for 7 days at normoxic conditions. The heart rate increased and oxygen saturation levels decreased with increasing altitude. Fibrinolysis and fibrinogen levels were not affected. Factor VIII and von Willebrand factor levels levels increased significantly in the active group, but not in the passive group. Plasma thrombin generation remained unchanged in both the active and passive group with increasing altitude and during 7 days of immobility in healthy subjects. However, by applying whole blood thrombin generation, we found an increased peak height and endogenous thrombin potential, and a decreased lagtime and time-to-peak with increasing levels of hypoxia in both groups. In conclusion, by applying whole blood thrombin generation we demonstrated that hypoxia causes a prothrombotic state. As thrombin generation in plasma did not increase, our results suggest that the cellular part of the blood is involved in the prothrombotic phenotype induced by hypoxia.

Original languageEnglish
Article numbere0141797
JournalPLoS ONE
Issue number10
Publication statusPublished - 30 Oct 2015
Externally publishedYes


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