Venous thrombosis at altitude presents with distinct biochemical profiles: a comparative study from the Himalayas to the plains

Abstract

High-altitude (HA) hypoxia exposure is believed to induce venous thromboembolism (VTE) in otherwise healthy individuals, although this needs to be fully established. The present study aims to ascertain the role of HA exposure in aggravating any predisposition toward VTE and to explore whether the etiology of HA-induced VTE is different from that of VTE closer to sea level. We compared manifestation-matched male VTE patients from HA (HAPs) and VTE patients from the plains closer to sea level (SLPs) for 54 parameters, including coagulation-related, fibrinolytic, and thrombophilic variables, as well as markers for stress and inflammatory response and platelet and endothelial activation. Our results established an association between HA hypoxia and VTE in alterations of primarily hemostatic variables. Approximately 96% of HAPs presented with ≥10 altered parameters out of 54 studied compared with 7% of SLPs. Elevated platelet count, von Willebrand factor, and clotting factors and altered coagulation exhibited significant associations with VTE events and altitude exposure (all P < .05). Additionally, most VTEs at HA were associated with younger age groups, unlike those on the plains. A receiver operator characteristic curve analysis revealed differences between HAPs and SLPs for CD40 ligand (area under the curve [AUC], 0.90; 95% confidence interval [CI], 0.84-0.96]), P-selectin (0.79; 0.70-0.88), platelet factor-4 (0.90; 0.84-0.96), intracellular adhesion molecule-1 (0.86; 0.79-0.93), vascular cell adhesion molecule-1 (0.97; 0.95-0.99), vascular endothelial growth factor (0.87; 0.8-0.94), FLT4 (0.94; 0.89-0.99), and Toll-like receptor-2 (0.98; 0.96-1.0) (all P < .05). In conclusion, this study suggests that HA exposure perturbs the molecules associated with vascular integrity and contributes to the early onset of VTE.

Conflict of interest statement

Conflict-of-interest disclosure: A.P. is a senior research fellow at Council of Scientific and Industrial Research/University Grants Commission. The remaining authors declare no competing financial interests.

© 2019 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Age distribution of the study patients. (A) Age class distribution of VTE patients. (B) Median (standard deviation) age of patients from both study groups with CVT, DVT, and PVT.

Figure 2.

Distribution of altered parameters in study patients. (A) Distribution of patients according to number of altered parameters. Patient-wise distribution of parameters altered from threshold cutoff in the HAP (B) and SLP (C) study groups. (D) Clustered distribution of the percentage of altered parameters in study groups. Filled circles represent HAP. Open circles represent SLP. Other parameters consist of hemostasis and inflammatory response.

Figure 3.

Association between HA hypoxia exposure and severity of prothrombotic episodes. ROC curve depicting the association of HA with VTE episodes as discrimination between HAPs (A) and SLPs (B) in terms of platelet and endothelial activation markers. (C) Correlation among platelet and endothelial activation molecules.