BLO2D Unlimited
The effect of repeated exercise at high altitude on blood coagulation

In The Netherlands, 2.9 per 1000 men and 1.7 per 1000 women per year suffer
from acute coronary syndrome (ACS), and in 4-10% of ACS cases, the patient had
exercised vigorously within 1 hour before onset. Strenuous exercise activates
blood coagulation, mostly due to elevated platelet count, platelet
hyperreactivity, increased thrombin generation and increased activity of
several coagulation factors, especially factor 8 (FVIII) and von Willebrand
factor (vWF). We corroborated these findings recently when testing healthy
subjects during an amateur bike race. The hypercoagulability may cause the
formation of coronary thrombi, provoking ACS.
Mountaineering also appears to pose a risk for developing thrombosis. Healthy
lowlanders moving to high altitude for a mean duration of 10 months were found
to have a 30 times increased risk of developing a venous thromboembolism (VTE).
Similarly, healthy soldiers stationed at high altitude were characterized by an
almost 25-fold increased risk of developing deep calf vein thrombosis. There
are little reports on the prevalence of coronary thrombosis or cerebrovascular
ischemia at high altitude. Our group recently investigated the effect of
hypobaric hypoxia on coagulation, by ascending from 50m to 3900m above sea
level. One group climbed actively and one group ascended passively by bus,
train and cable car. Blood samples were taken at different altitudes. Thrombin
generation measured in whole blood proved to rise with increasing altitude.
This indicates that hypobaric hypoxia at high altitude causes
hypercoagulability, irrespective of the exercise, and may contribute to the
occurrence of thrombosis.
Mountaineering usually involves repeated strenuous exercise, when walking,
climbing, skiing or cycling. Because hypoxia and exercise both cause
procoagulant changes, one might expect that exercise will amplify the
altitude-induced hypercoagulability. This would put susceptible individuals at
more risk of developing ACS. However, in a small study in 2004 it was found
that hypoxia actually attenuates the exercise-induced procoagulant changes.
More specifically, an augmented fibrinolytic response, measured by absence of
plasmin activator inhibitor (PAI-1) elevation was found. Additionally, recently
our group performed a pilot study, subjecting healthy volunteers to strenuous
exercise during 3 consecutive days. We found that exercise indeed induces
procoagulant changes, but that these were attenuated during the repeated
exposure [not published]. These findings prompt further research.
Our group is specialized in measuring markers of coagulation in unusual
circumstances, for instance during high altitude expeditions or during cycling
competitions. Furthermore, we have recently developed an assay for measuring
plasmin generation [not published]. Plasmin is responsible for breaking down
the fibrin network (fibrinolysis). Using the specific knowledge and know-how of
our lab, we will further unravel the effect of hypoxia combined with repeated
strenuous exercise on blood coagulation.

To investigate the effect of monitored strenuous exercise at high altitude on
blood coagulation, more specifically on thrombin generation, platelet function
and fibrinolysis.

6 healthy male volunteers, 18 - 50 years old, will exert strenuous exercise
(measured by a heart rate reserve of 60-85%) during 2 hours on an exercise
bike, both at sea level (normoxia) and at 3,883 m above sea level (hypobaric
hypoxia), which will be repeated on 3 consecutive days. Blood samples will be
drawn just before and immediately after the exercise.
Between the baseline exercise test at sea level and the hypoxic exercise tests,
volunteers will acclimatise to the altitude for 5 days according to a fixed
schedule.

Strenuous physical exercise during 2 hours on an exercise bicycle at 4,000 m
above sea level. The heart rate will be monitored during the exercise and
targeted at a heart rate reserve of 60 to 85%. The exercise test will be
repeated on 3 consecutive days.

As a control, participants will undergo the same exercise test at sea level
once.

- All volunteers will undergo an exercise stress test by a cardiologist prior
to the start of the study, to ensure that all participants are physically
healthy.
- Eight blood samples of 27 ml each will be drawn, which poses a risk of
developing a local bruise or hematoma.
- Mountaineering poses a risk of developing acute mountain sickness (AMS), a
clinical syndrome ranging from dizziness, nausea and lethargy to ataxia,
vomiting and unconsciousness. Participants will be accompanied by at least 1
medical doctor at high altitude and emergency care will be delivered if
necessary. Symptoms of AMS will be screened for daily by using the Lake Louise
AMS questionnaire. An experienced mountain guide will be present. Participants
will be escorted back to sea level immediately if AMS symptoms are present.