Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a pro-thrombotic phenotype but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatising to high altitude (5200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of subjects following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen
concentration that occurred during acclimatisation. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100™ closure times and increased platelet aggregation in response to ADP. Post-expedition results were consistent with the normalisation of coagulation following descent to sea-level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a pro-thrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events.