Exposure to High Altitude: A Risk Factor for Venous Thromboembolism?

Abstract

There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several previous studies have suggested that conditions present at HAs contribute to establish a prothrombotic milieu, published reports are contradictory and the exact underlying mechanism remains poorly understood. Results from HA studies also show that environmental conditions at HA such as hypoxia, dehydration, hemoconcentration, low temperature, use of constrictive clothing as well as enforced stasis due to severe weather, would support the occurrence of thrombotic disorders. The three leading factors of Virchow triad, that is, venous stasis, hypercoagulability, and vessel-wall injury, all appear to be present at HA. In synthesis, the large list of environmental variables suggests that a single cause of HA-induced thromboembolic disorders (TED) may not exist, so that this peculiar phenomenon should be seen as a complex or multifactorial trait. Further investigation is needed to understand the risk of TED at HA as well as the possible underlying mechanisms.

Altered expression of platelet proteins and calpain activity mediate hypoxia-induced prothrombotic phenotype

“…A flow cytometry-based approach was used for analyzing the surface expression of CD41 and aIIbb 3 . The anti-aIIbb 3 antibody that interacts with the aIIbb 3 receptor complex 28 demonstrated an enhanced surface expression of this complex that reflects greater platelet activation on induction with ADP in exposed animals than that seen in controls ( Figure 3A,C). CD41, another platelet activation marker, also exhibited a similar response ( Figure 3B,D).…”

“…[1][2][3][4][5] In the case of highaltitude hypoxic exposure, both venous as well as arterial thrombotic events can occur, which include pulmonary thromboembolism, cerebral venous thrombosis, portal vein thrombosis, aortic thrombosis, stroke, and transient ischemic attack. [6][7][8][9] At extreme altitude, adverse environmental conditions including hypobaric hypoxia and cold may facilitate the development of the corresponding prothrombotic phenotype.…”

Hormonal Contraceptives and Travel to High Altitude

“…High altitude exposure alone may be an independent risk factor for thrombosis (Anand, 2001;Segler, 2001). Many case reports document thromboembolic events occurring at high altitude, but the mechanism and the role of hypobaric hypoxia in these events remains uncertain (reviewed in Gupta and Ashraf, 2012). No systematic data on the combined risk of altitude and HC exist.…”

“…These include dehydration, immobility in mountaineers who may be stranded in tents for long periods due to weather, cold effects on peripheral perfusion, hemo-concentration, thrombocytosis, and possibly other effects of hypoxia (Gupta and Ashraf, 2012).…”

PAI-1 polymorphism as a cause of severe high altitude associated arteriovenous thrombosis

“…There are multiple case reports of pulmonary embolism, renal artery/vein occlusion, cerebrovascular accidents on exposure to high altitude 1. There are a very few case series or randomised trials that report the exact aetiopathogenesis of thrombosis.…”