# High-altitude thrombosis: divergent pathophysiological mechanisms and preventive strategies in acutely exposed population and native highlanders

## TL;DR

This review explains how high-altitude exposure increases blood clot risk differently in newcomers and long-term residents, and suggests tailored prevention strategies for each group.

## Contribution

The paper highlights divergent pathophysiological mechanisms and population-specific preventive strategies for high-altitude thrombosis.

## Key findings

- Acute high-altitude exposure increases thrombosis risk through hypoxia-induced inflammation and blood viscosity changes.
- High-altitude natives have protective adaptations, but extreme conditions can still cause hyperviscosity and clotting risks.
- Population-specific prevention strategies, such as acclimatization for newcomers and monitoring for natives, are recommended.

## Abstract

High-altitude environments pose distinct physiological challenges, with marked differences in the thrombotic responses between high-altitude acutely exposed individuals (HAAEI) and long-term high-altitude natives (HAN). This narrative review explores the divergent mechanisms underlying thrombosis in these two populations, aiming to deepen understanding of hypoxia-induced vascular risk.

Acute high-altitude exposure elicits a cascade of responses—including sympathetic overactivation, inflammation, polycythemia, increased blood viscosity, and endothelial dysfunction—that collectively heighten thrombosis risk. Central to this process is the hypoxia-mediated interaction of HIF with NF-κB pathways, which fosters a proinflammatory and procoagulant milieu characterized by cytokine upregulation, enhanced platelet activation, and suppressed fibrinolysis. Conversely, HAN exhibit genetic and physiological adaptations—such as improved oxygen utilization and hematological efficiency—that confer relative protection. However, extreme hypoxia or dehydration can override these adaptations, triggering pathological hyperviscosity. Prevention strategies for HAAEI include gradual acclimatization, hydration, and activity moderation, while HAN may benefit from routine hematological monitoring and, if necessary, antithrombotic interventions.

Hypoxia-induced alterations in inflammation and blood rheology play pivotal roles in high-altitude thrombosis. Population-specific prevention strategies are essential, and further research is needed to refine pathophysiological understanding and guide targeted interventions.