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

Dana Huskens,Suzanne Zwaveling,Lisa N Van Der Vorm,Bas De Laat,Jasper A Remijn,Evi Schoenmaker,Cécile H Kicken

doi:10.1055/s-0039-1692991

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.

Highlights

Physical exercise is protective against cardiovascular disease, it can provoke sudden cardiac death
Strenuous exercise induces a procoagulant state that is mediated by the endothelium, by increasing von Willebrand factor (VWF) and secondarily raising factor VIII (FVIII) levels
A few studies found that systemic hypoxia influences hemostasis through the elevation of FVIII levels, as that occurs in response to strenuous exercise.[13,14]

Summary

Introduction

Physical exercise is protective against cardiovascular disease, it can provoke sudden cardiac death (exercise paradox). Epidemiological studies suggest that systemic hypoxia at high altitude is a risk factor for venous thromboembolism. Physical exercise is generally protective against cardiovascular events, there are numerous reports of exercise-related thromboembolic and cardiovascular events.[1,2,3] it has been found that high altitude increases the risk of venous thromboembolism (VTE).[4,5,6,7] cardiac arrest at high altitude due to coronary thrombosis has been reported.[8]. A few studies found that systemic hypoxia influences hemostasis through the elevation of FVIII levels, as that occurs in response to strenuous exercise.[13,14] It has long been known that elevated FVIII levels are a risk factor for VTE, likely by increasing TG. The anticoagulant vitamin E prevented increases in both FVIII and TG following 2 hours of exposure to normobaric hypoxia.[14]

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