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.

Thirty Minutes of Hypobaric Hypoxia Provokes Alterations of Immune Response, Haemostasis, and Metabolism Proteins in Human Serum

“…Hypoxia is known to be associated with deep vein thrombosis [ 44 ] and venous thromboembolism [ 45 ]. The link between long-haul air travel and venous thromboembolism is a subject of continuing debate [ 46 ].…”

Identification of regulatory microRNAs for hypoxia induced coagulation mechanism byIn-silicoanalysis

“…During conditions of physiological stress, such as hypoxia, the body is more susceptible to succumb to pro-thrombotic state like those at high altitudes. Hypoxia acts as a trigger for activating the genes of coagulation cascade, regardless of the physical activity (19). Various studies have shown that hypoxia predisposes the homeostasis shift towards a pro-coagulative milieu.…”

“…However, exposure to hypoxic stress can increase the risk of developing thrombosis by hypoxia-induced platelet aggregation and activation of blood coagulation cascade (5). Hypoxia has been demonstrated to create a pro-thrombotic milieu by an increase in thrombin generation in whole blood even in absence of physical exercise (6). As platelet activation is the primary cause of hemostatsis during vascular injury, substantial evidences demonstrate platelet activation and an increase in platelet adhesiveness in healthy volunteers on exposure to hypoxia (7).…”

Effects of Repeated Bouts of Exercise on the Hemostatic System

“…To characterize changes in their hemostatic profile, we measured VWF (total antigen, 126 VWF propeptide, 62 and active VWF) levels, FVIII, 126,127 thrombin generation, 128 fibrinogen levels, 127 platelet activation, 129 and clot lysis time 127 (methods according to references). Peripheral blood cell counts in citrated whole blood were determined using a COULTER counter analyzer (Beckman Coulter, Woerden, the Netherlands).…”

“…(D) FVIII activity was measured as described previously. 126,127 All measurements were performed in triplicate, and data represent the mean AE standard deviation (SD) (n ¼ 5).…”