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Hemostasis in highlanders with excessive erythrocytosis at 5100 m: Preliminary data from the highest city of the world

https://doi.org/10.1016/j.resp.2020.103535Get rights and content

Highlights

  • Hemostasis status of high-altitude residents is unknown.

  • Coagulation was assessed in highlanders with or without excessive erythrocytosis (EE).

  • Highlanders with EE had lower bleeding and coagulation times.

  • Highlanders with EE appear to present a state of hypercoagulability.

Abstract

Little is known about hemostasis modifications induced by chronic hypoxic exposure in high-altitude residents, especially in those who develop excessive erythrocytosis (EE, i.e. hemoglobin concentration ≥ 21 g·dL−1 in male and ≥ 19 g·dL-1 in female). The aim of this preliminary study was to assess coagulation alterations in highlanders with or without EE using simple hemostatic tests such as bleeding (BT) and clotting (CT) times. Eighty-one male (43 ± 7 years), permanent residents from La Rinconada (Peru), the highest city in the world (5,100−5,300 m), were evaluated. Thirty-six subjects (44 %) presented with EE. EE subjects compared to non-EE subjects had lower BT (3.6 ± 1.2 vs. 7.0 ± 1.9 min, p < 0.001) and CT (11.7 ± 1.7 vs. 15.1 ± 2.3 min, p < 0.001). These results support the notion that highlanders with EE are in a state of hypercoagulability and call for further hemostasis investigations in this population using more detailed hemostatic methods.

Introduction

Chronic hypoxic exposure is a physiological challenge faced by permanent residents at high-altitude (HA) that can lead in some highlanders to excessive erythrocytosis (EE) and chronic mountain sickness (CMS) (Villafuerte and Corante, 2016). If the respiratory or cardio-vascular consequences of acute and chronic HA exposure have been deeply investigated, data regarding the impact of chronic hypoxia on the coagulation cascade are scarce and concern almost exclusively acute HA exposure in lowlanders. In these acute conditions, HA exposure seems to induce a prothrombotic state (Rocke et al., 2018; Zavanone et al., 2017), although this remains debated (Crosby et al., 2003).The consequences of chronic HA exposition on hemostasis in highlanders remains unexplored.

Older yet validated and easy-to-use hemostatic measurements such as bleeding (BT) and clotting (CT) times could represent suitable alternative to more complex albeit extensive investigations that are unfortunately difficult to perform reliably in such extreme conditions and cannot realistically be scaled up in HA low-resource conditions (Bowie and Owen, 1980; Sussman, 1973).

Therefore, this study aims to investigate for the first-time hemostasis in a unique population of highlanders living in the highest city in the world, La Rinconada (5,100−5,300 m), with or without EE. We hypothesized that highlanders with EE would exhibit shorter BT and CT suggesting a state of hypercoagulability.

Section snippets

Participants

Eighty-one males residing permanently in La Rinconada (a gold mining town located in Southern Peru at an altitude of 5100−5300 m and considered the highest city in the world (West, 2002) were included in the present study after written informed consent. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethic committee of the National University of San Marcos, Lima, Peru (Protocol number: CIEI-2019−002).

Data collection

Subjects’ baseline characteristics were first

Results

Demographic characteristics of the subjects are summarized in the Table 1. No significant difference in demographic characteristics was observed between participants with or without EE, except BMI. By design, hematocrit and [Hb] levels were different between groups. All highlanders were born at HA (>3500 m) and resided in La Rinconada for 16 ± 11 years. They reported no medication intake, no medical history of chronic respiratory, cardiovascular and hematological diseases and none of them

Discussion

We reported significantly lower BT and CT in highlanders with EE compared to highlanders without EE who lived in the highest city of the world at 5100−5300 m. These data suggest a potential hypercoagulability status in EE highlanders without any past history of symptomatic thrombosis. This preliminary study represents to our knowledge the first report of hemostasis investigation in the setting of permanent HA exposure, since previous studies only focused on transient HA stay in lowlanders (

Author contributions

IH, BC, ES, AP, PR, JVB, YS, SD, PC and SV designed the study, analyzed and interpreted the data. IH and SV acquired the data. BC and SV performed the statistical analysis. IH and BC wrote the manuscript; SV and PC revisited it for important intellectual content. All authors approved the final version of the manuscript.

Funding source

This study was supported by the Grenoble Alpes University foundation, the “Fonds de dotation AGIR pour les maladies chroniques” and by the French National Research Agency (ANR-12-TECS-0010) in the framework of the “Investissements d’avenir” program (ANR-15-IDEX-02).

Acknowledgments

We thank the voluntary residents of La Rinconada for their personal participation to the study as well as the medical students of the Altiplano University (Puno, Peru) who actively participated to the research program implemented in La Rinconada.

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