PB1041 - Hypoxia increases coagulation which is more pronounced in women but is counterbalanced by a decreased platelet reactivity

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Marisa Ninivaggi, PhD

Research Project Leader
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Co-Author(s)

HM

Harmen Middelveld

Research Technician
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands Synapse Research Institute, Maastricht, The Netherlands.
Maastricht, Limburg, Netherlands
VS

Veronica Schmalschlager

Research Technician
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands Synapse Research Institute, Maastricht, The Netherlands.
Maastricht, Limburg, Netherlands
Mark Roest, PhD

Clinical Director
Department of Platelet pathophysiology, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Romy De Laat-Kremers, PhD

Post-doctoral Research Project Leader
Department of Data Analysis and Artificial Intelligence, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Bd

Bas de Laat, MD, PhD

General Director
Department of Functional Coagulation, Synapse Research Institute, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands

Background: Hypoxia plays an important role in many pathologies, as e.g. chronic obstructive pulmonary disease and obstructive sleep apnea syndrome. These conditions are associated with an increased thrombosis risk and oxygen desaturation seems to be one of the major mediators of hypercoagulability.

Aims: The objective was to investigate the effect of exercise on thrombin generation (TG) and platelet activation under hypoxic conditions at high altitude.

Methods: Ten healthy volunteers were recruited for this study (50% male, mean age of 33 years). The study was conducted in two phases in which the subjects went up to an altitude of 3883m firstly by cable car (passively), and secondly by walking (actively).

Results: As expected for both the passive and active ascend, the oxygen saturation decreased, while the heart rate increased significantly at high altitude (p < 0.005 and p< 0.05, respectively). Acute mountain sickness symptoms were observed independently of the ascend method. After the active ascend, platelet, white blood cell and granulocyte count were increased (p=0.0051, p< 0.0007, and p=0.0001, respectively), and lymphocyte was decreased (p < 0.0001). FVIII and von Willebrand factor were significantly increased after the active ascent (VWF, p=0.0001 and p=0.0016, respectively). TG analysis showed a prothrombotic trend at high altitude, especially after the active ascend. Interestingly, women had a more prothrombotic phenotype compared to men (Figure 1), indicated by a significantly higher peak height and ETP, and shorter lagtime, time-to-peak and velocity index. ETP inhibition by thrombomodulin was lower in women after the active ascend, albeit not significantly. Interestingly, platelet activation was reduced and delayed (p=0.0073 and p=0.0146, respectively) after the active ascend.

Conclusion(s): Hypoxia increased TG, as well as FVIII and VWF due to exercise. Women had a more prothrombotic phenotype compared to men, which was more defined at high altitude. We theorized that the observed hypercoagulability is counterbalanced by decreasing platelet activation.