High altitude has been linked to noticeably more thromboembolic events, according to studies. Although transferrin has been shown to increase blood coagulation, the exact mechanism underlying high altitude-related thromboembolism was unknown. For a study, researchers sought to determine the levels of transferrin and plasma coagulation factors in plasma taken from long-term human residents and transient mice exposed to a range of elevations.
They discovered that high altitude greatly raised the activity of thrombin and factor XIIa (FXIIa), as well as the quantities of transferrin in the plasma of humans and mice. Additionally, hypoxia (6% O2) and low temperature (0°C), two essential high-altitude factors, increased the levels of hypoxia-inducible factor 1α (HIF-1α), which promoted the expression of the transferrin gene and contained a HIF-1α binding site in its enhancer region. This, in turn, caused hypercoagulability by amplifying thrombin and FXIIa.
Importantly, transferrin interferences, such as transferrin antibody treatment, transferrin downregulation, and the administration of the designed peptides that inhibited the potentiation of transferrin on thrombin and FXIIa, alleviated thromboembolic disorders and pathological insults in mouse models induced by both hypoxia and low temperature. As a result, hypoxia and low temperature increased transferrin expression, which encouraged hypercoagulability.
The findings indicated that thromboembolic events brought on by negative environmental variables in high-altitude environments could be prevented by targeting the transferrin-coagulation pathway.
