scholarly journals Hypobaric Hypoxia Induces Hypercoagulability Due to an Increase in Microparticles

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3549-3549
Author(s):  
Cécile H. Kicken ◽  
Marisa Ninivaggi ◽  
Joke Konings ◽  
Martijn Moorlag ◽  
Leslie In het Panhuis ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sea Level ◽  
Platelet Activation ◽  
Whole Blood ◽  
Hypobaric Hypoxia ◽  
Statistical Significance ◽  
Acute Mountain Sickness ◽  
Peak Height ◽  
Mountain Sickness

Abstract Studies investigating the role of hypoxia on coagulation, either by going to high altitude or after a long-haul flight, reveal contrasting results. Previous work from our group suggests that the cellular part of the blood is involved in causing a prothrombotic phenotype. Therefore this study investigated the effect of hypobaric hypoxia on blood coagulation, focusing on the role of cellular components. After approval from the local medical ethics committee, 16 healthy participants (aged 20 to 50 years old) were included in this study. Exclusion criteria were a history of cardiovascular disease or pulmonary disease, impaired mobility, and medication known to interfere with coagulation. Participants ascended by cable car to 3,883 meters above sea level, after acclimatizing to altitude for 6 days. At 50 meters and 3,883 meters above sea level, blood was drawn and vital signs (SpO2, heart rate) and the Lake Louise acute mountain sickness questionnaire (LLQ) were recorded. The following tests were performed on whole blood: hemoglobin (Hb), hematocrit (Ht), leucocyte count (L), platelet count (PC) and mean platelet volume (MPV); thrombin generation (TG) in whole blood (WB-TG) with 0.5 pM tissue factor (TF); platelet activation test (PAc-T) triggered by adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and collagen related peptide (CRP) in end concentrations of respectively 10 µM, 30 µM and 1 µg ml-1. The remainder of the blood was centrifuged to obtain platelet rich plasma (PRP) (once for 15 minutes at 230 g) and platelet poor plasma (PPP) (twice for 10 minutes at 2,821 g). PRP was used to test PRP-TG (1 pM TF) and plasma was used for PPP-TG (1 pM TF) and microparticles (MP)-TG (0 pM TF). The paired t-test with p <0.05 was used to determine statistical significance within participants. At 3,883 meters above sea level, oxygen saturation decreased and heart rate increased significantly. LLQ scores revealed mild acute mountain sickness (AMS) symptoms. One participant was withdrawn from the study at 3,030 meters due to moderate AMS. After applying TG in PPP, PRP and whole blood, we found that peak height and endogenous thrombin potential (ETP) were increased. Interestingly, we found a decrease in platelet activation and a decreased MPV. To find an explanation for the increased TG in the different media, we performed a TG assay specially designed to detect microparticles. As with the PPP-TG, PRP-TG and WB-TG, we found an increase in ETP and peak height, proving increased content of MPs. In conclusion, we found that exposure to hypobaric hypoxia increased TG in PPP, PRP and in whole blood. In contrast we found that platelet activation was decreased, indicating that platelets do not play a role in hypoxia-induced hypercoagulability. The increase in peak and ETP in the MP-sensitive TG assay indicates that MPs play a major role in hypoxia-induced hypercoagulability. Disclosures De Laat: Synapse bv: Employment.

Hypobaric Hypoxia Causes Elevated Thrombin Generation Mediated by FVIII that is Balanced by Decreased Platelet Activation

2018 ◽  
Vol 118 (05) ◽  
pp. 883-892 ◽  
Author(s):  
Marisa Ninivaggi ◽  
Joke Konings ◽  
Martijn Moorlag ◽  
Dana Huskens ◽  
Jasper Remijn ◽  
...  
Keyword(s):  
Factor Viii ◽  
High Altitude ◽  
Sea Level ◽  
Platelet Activation ◽  
Whole Blood ◽  
Hypobaric Hypoxia ◽  
Thrombin Generation ◽  
Acute Mountain Sickness ◽  
Blood Platelet ◽  
Platelet Poor Plasma

Introduction Epidemiological studies suggest that hypobaric hypoxia at high altitude poses a risk for developing venous thromboembolism. The cause of this observed hypercoagulability remains unclear. Therefore, this study aimed to investigate the effect of hypobaric hypoxia at 3,883 m above sea level on thrombin generation and platelet activation. Methods After complying with medical ethical procedures, 18 participants were recruited, of whom 1 had to leave the study prematurely due to mild acute mountain sickness. Blood was drawn first at 50 m above sea level and second at 3,883 m altitude after gradual acclimatization for 6 days. Thrombin generation was measured in whole blood, platelet-rich plasma and platelet-poor plasma. Platelet activation was assessed using a whole blood flow-cytometric assay. Coagulation factor levels, D-dimer levels and markers of dehydration and inflammation were measured. Results Hypobaric hypoxia at 3,883 m altitude caused increased thrombin generation, measured as peak height and endogenous thrombin potential, in whole blood, platelet-rich and platelet-poor plasma without or at low tissue factor concentration. The elevated thrombin generation was mediated by increased factor VIII levels and not caused by dehydration or inflammation. In contrast, spontaneous and agonist-induced platelet activation was decreased at high altitude. Conclusion Hypobaric hypoxia causes increased factor VIII-mediated thrombin generation. The hypercoagulability was balanced by decreased platelet activation. These findings may explain why venous, and not arterial thrombotic events occur more frequently at high altitude.

Effect of repeated normobaric hypoxia exposures during sleep on acute mountain sickness, exercise performance, and sleep during exposure to terrestrial altitude

2011 ◽  
Vol 300 (2) ◽  
pp. R428-R436 ◽  
Author(s):  
Charles S. Fulco ◽  
Stephen R. Muza ◽  
Beth A. Beidleman ◽  
Robby Demes ◽  
Janet E. Staab ◽  
...  
Keyword(s):  
Heart Rate ◽  
Exercise Performance ◽  
Hypobaric Hypoxia ◽  
Sham Group ◽  
Acute Mountain Sickness ◽  
Time Trial ◽  
Normobaric Hypoxia ◽  
Performance Decrement ◽  
Mountain Sickness ◽  
End Tidal

There is an expectation that repeated daily exposures to normobaric hypoxia (NH) will induce ventilatory acclimatization and lessen acute mountain sickness (AMS) and the exercise performance decrement during subsequent hypobaric hypoxia (HH) exposure. However, this notion has not been tested objectively. Healthy, unacclimatized sea-level (SL) residents slept for 7.5 h each night for 7 consecutive nights in hypoxia rooms under NH [ n = 14, 24 ± 5 (SD) yr] or “sham” ( n = 9, 25 ± 6 yr) conditions. The ambient percent O2 for the NH group was progressively reduced by 0.3% [150 m equivalent (equiv)] each night from 16.2% (2,200 m equiv) on night 1 to 14.4% (3,100 m equiv) on night 7, while that for the ventilatory- and exercise-matched sham group remained at 20.9%. Beginning at 25 h after sham or NH treatment, all subjects ascended and lived for 5 days at HH (4,300 m). End-tidal Pco2, O2 saturation (SaO2), AMS, and heart rate were measured repeatedly during daytime rest, sleep, or exercise (11.3-km treadmill time trial). From pre- to posttreatment at SL, resting end-tidal Pco2 decreased ( P < 0.01) for the NH (from 39 ± 3 to 35 ± 3 mmHg), but not for the sham (from 39 ± 2 to 38 ± 3 mmHg), group. Throughout HH, only sleep SaO2 was higher (80 ± 1 vs. 76 ± 1%, P < 0.05) and only AMS upon awakening was lower (0.34 ± 0.12 vs. 0.83 ± 0.14, P < 0.02) in the NH than the sham group; no other between-group rest, sleep, or exercise differences were observed at HH. These results indicate that the ventilatory acclimatization induced by NH sleep was primarily expressed during HH sleep. Under HH conditions, the higher sleep SaO2 may have contributed to a lessening of AMS upon awakening but had no impact on AMS or exercise performance for the remainder of each day.

Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man

1995 ◽  
Vol 133 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Ettore C degli Uberti ◽  
Maria R Ambrosio ◽  
Marta Bondanelli ◽  
Giorgio Transforini ◽  
Alberto Valentini ◽  
...  
Keyword(s):  
Heart Rate ◽  
Healthy Subjects ◽  
Sympathetic Nerve Activity ◽  
Heart Rate Response ◽  
Statistical Significance ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Nerve Activity ◽  
Receptor Stimulation

degli Uberti EC, Ambrosio MR, Bondanelli M, Trasforini G, Valentini A, Rossi R, Margutti A, Campo M. Effect of human galanin on the response of circulating catecholamines to hypoglycemia in man. Eur J Endocrinol 1995;133:723–8. ISSN 0804–4643 Human galanin (hGAL) is a neuropeptide with 30 amino acid residues that has been found in the peripheral and central nervous system, where it often co-exists with catecholamines. In order to clarify the possible role of hGAL in the regulation of sympathoadrenomedullary function, the effect of a 60 min infusion of hGAL (80 pmol·kg−1 · min−1) on plasma epinephrine and norepinephrine responses to insulin-induced hypoglycemia in nine healthy subjects was investigated. Human GAL administration significantly reduced both the release of basal norepinephrine and the response to insulin-induced hypoglycemia, whereas it attenuated the epinephrine response by 26%, with the hGAL-induced decrease in epinephrine release failing to achieve statistical significance. Human GAL significantly increased the heart rate in resting conditions and clearly exaggerated the heart rate response to insulin-induced hypoglycemia, whereas it had no effect on the blood pressure. We conclude that GAL receptor stimulation exerts an inhibitory effect on basal and insulin-induced hypoglycemia-stimulated release of norepinephrine. These findings provide further evidence that GAL may modulate sympathetic nerve activity in man but that it does not play an important role in the regulation of adrenal medullary function. Ettore C degli Uberti, Chair of Endocrinology, University of Ferrara, Via Savonarola 9, I-44100 Ferrara, Italy

Elevated plasma S100B levels in high altitude hypobaric hypoxia do not correlate with acute mountain sickness

2014 ◽  
Vol 36 (9) ◽  
pp. 779-785 ◽  
Author(s):  
Craig D. Winter ◽  
Timothy R. Whyte ◽  
John Cardinal ◽  
Stephen E. Rose ◽  
Peter K. O’Rourke ◽  
...  
Keyword(s):  
High Altitude ◽  
Hypobaric Hypoxia ◽  
Acute Mountain Sickness ◽  
Elevated Plasma ◽  
Mountain Sickness

scholarly journals Heart rate variability changes at 2400 m altitude predicts acute mountain sickness on further ascent at 3000–4300 m altitudes

2012 ◽  
Vol 3 ◽  
Author(s):  
Heikki M. Karinen ◽  
Arja Uusitalo ◽  
Henri Vähä-Ypyä ◽  
Mika Kähönen ◽  
Juha E. Peltonen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Heart Rate Variability ◽  
Acute Mountain Sickness ◽  
Mountain Sickness

Intracranial Pressure at High Altitude and Acute Mountain Sickness

1995 ◽  
Vol 89 (2) ◽  
pp. 201-204 ◽  
Author(s):  
A. D. Wright ◽  
C. H. E. Imray ◽  
M. S. C. Morrissey ◽  
R. J. Marchbanks ◽  
A. R. Bradwell
Keyword(s):  
Intracranial Pressure ◽  
High Altitude ◽  
Acute Hypoxia ◽  
Acute Mountain Sickness ◽  
Raised Intracranial Pressure ◽  
Rapid Ascent ◽  
Mountain Sickness ◽  
Pressure Changes ◽  
Serial Measurements

1. Raised intracranial pressure has been noted in severe forms of acute mountain sickness and high-altitude cerebral oedema, but the role of intracranial pressure in the pathogenesis of mild to moderate acute mountain sickness is unknown. 2. Serial measurements of intracranial pressure were made indirectly by assessing changes in tympanic membrane displacement in 24 healthy subjects on rapid ascent to 5200 m. 3. Acute hypoxia at 3440 m was associated with a rise in intracranial pressure, but no difference was found in pressure changes at 4120 or 5200 m in subjects with or without symptoms of acute mountain sickness. 4. Raised intracranial pressure, though temporarily associated with acute hypoxia, is not a feature of acute mountain sickness with mild or moderate symptoms.

Sign in / Sign up

Export Citation Format

Share Document