title: Hypoxia Induces a Prothrombotic State Independently of the Physical Activity.
abstract: 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.
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ninivaggi
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: de Laat
authors.affiliation: Department of Anesthesiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marcus M D
authors.initials: MM
authors.lastname: Lancé
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Anesthesiology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Cécile H
authors.initials: CH
authors.lastname: Kicken
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Leonie
authors.initials: L
authors.lastname: Pelkmans
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Bloemen
authors.affiliation: Department of NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marlou L
authors.initials: ML
authors.lastname: Dirks
authors.affiliation: Department of NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.affiliation: Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: José W P
authors.initials: JW
authors.lastname: Govers-Riemslag
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Lindhout
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Joke
authors.initials: J
authors.lastname: Konings
authors.affiliation: Department of Synapse bv, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Biochemistry, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
mesh_terms: D000328:Adult; D000532:Altitude Sickness / Q000097:blood* / Q000503:physiopathology; D001794:Blood Pressure; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D011516:Prothrombin / Q000378:metabolism*
chemical_list: D011516:Prothrombin; D005340:Fibrinogen