The Influence of Environmental Hypoxia on Hemostasis—A Systematic Review

Abstract

Humans have been ascending to high altitudes for centuries, with a growing number of professional- and leisure-related sojourns occurring in this millennium. A multitude of scientific reports on hemostatic disorders at high altitude suggest that hypoxia is an independent risk factor. However, no systematic analysis of the influence of environmental hypoxia on coagulation, fibrinolysis and platelet function has been performed. To fill this gap, we performed a systematic literature review, including only the data of healthy persons obtained during altitude exposure (<60 days). The results were stratified by the degree of hypoxia and sub-categorized into active and passive ascents and sojourns. Twenty-one studies including 501 participants were included in the final analysis. Since only one study provided relevant data, no conclusions regarding moderate altitudes (1,500–2,500 m) could be drawn. At high altitude (2,500–5,400 m), only small pathophysiological changes were seen, with a possible impact of increasing exercise loads. Elevated thrombin generation seems to be balanced by decreased platelet activation. Viscoelastic methods do not support increased thrombogenicity, with fibrinolysis being unaffected by high altitude. At extreme altitude (5,400–8,850 m), the limited data showed activation of coagulation in parallel with stimulation of fibrinolysis. Furthermore, multiple confounding variables at altitude, like training status, exercise load, fluid status and mental stress, prevent definitive conclusions being drawn on the impact of hypoxia on hemostasis. Thus, we cannot support the hypothesis that hypoxia triggers hypercoagulability and increases the risk of thromboembolic disorders, at least in healthy sojourners.

Effects of the Omicron variant of coronavirus disease 2019 on anaemia treatment for patients undergoing peritoneal dialysis

“…Currently, real-world research does not support the hypothesis that roxadustat leads to increased thrombosis or increased platelet count. 24,25 It is currently unclear whether HIF-PHI increases the risk of thrombotic events in patients infected with coronavirus. However, in the process of correcting anaemia, it is important to control Hb levels within an appropriate range while avoiding sharp fluctuations in Hb levels.…”

“…Hypoxia itself promotes thrombosis, and the HIF system can be activated under conditions that promote thrombosis. Currently, real‐world research does not support the hypothesis that roxadustat leads to increased thrombosis or increased platelet count 24,25 . It is currently unclear whether HIF‐PHI increases the risk of thrombotic events in patients infected with coronavirus.…”

Hypoxia-Inducible Factor–Prolyl Hydroxyl Domain Inhibitors: From Theoretical Superiority to Clinical Noninferiority Compared with Current ESAs?

“…Moreover, hypoxia itself is thrombogenic, 97 , 98 and the HIF system can be activated in prothrombotic conditions 99 . Nevertheless, studies performed at high altitudes do not seem to support increased thrombogenicity 100 or increased platelet count 101 . A metanalysis of 30 studies ( n =13,146) showed a higher risk for thrombotic events when using HIF-PHIs than placebo or ESAs 46 .…”

The Benefits of Early Continuous Renal Replacement Therapy in Critically Ill Patients with Acute Kidney Injury at High-Altitude Areas: A Retrospective Multi-center Cohort Study

“…However, current CRRT prescription in high altitude is largely based on physicians' experiences because CRRT in high altitude may have different adverse and curative effects on AKI from that in low altitude. On the one hand, previous studies found that long-term environmental hypoxia was an independent factor in coagulation dysfunction, hemostatic disorders and thrombocytopenia at high altitude [12][13][14]. Su cient use of anticoagulants in CRRT, which is required to prevent circuit clotting to maintain lter performance, is more likely to increase the bleeding risks and other adverse events in high altitude [1,7].…”