MARKERS OF THROMBIN ACTIVATION UNDER HYPOBARIC HYPOXIA EXPOSURE AT EXTREME ALTITUDE. PROFILE CHANGES OF WHOLE BLOOD ROTATION THROMBOELASTOMETRY

OBJECTIVE. Environmental and logistic difficulties usually limit the study of haemostatic changes at high altitude because the assessment of the response of single components of blood coagulation and fibrinolysis require different assays and the correct transport of blood samples back to the laboratory. The present study was performed to investigate the simultaneous and integrated effects of different components involved in the dynamic process of coagulation during exposition to high altitude with the use of whole blood thromboelastometry, taking advantage of the HIGH altitude Cardiovascular Research (HIGHCARE) project at Everest base camp (BC) . DESIGN AND METHOD. Forty seven healthy volunteers (31 males and 16 females) aged 24-62 years (40±9 years) participating in the expedition to Everest BC (september 2008) were investigated. Citrated blood samples were withdrawn at sea level (baseline), the day after reaching 3300 m (Namche), and the day after the arrival and after two weeks at 5400 m (Everest BC1 and BC2 respectively). Just before running thromboelastometry (Pentapharm, Munich, Germany), citrated blood samples were recalcified with CaCl2. To assess activation and inhibition of coagulation sensitively we did not add an exogenous agonist to the test system (no agonist thromboelastometry). The following variables were analyzed: coagulation time (CT), clot formation time (CFT), alpha angle, and maximum-clot-firmness (MCF). RESULTS. Ascent to 3300 m was not associated with significant changes in thromboelastometry variables. Conversely, the day after reaching Everest BC (BC1) a significant reduction of both CT and CFT time with a simultaneous increase of alpha angle (p<0.001 for all) was observed. These variables returned to baseline values after two weeks (BC2) when haematocrit and MCF were found to be significantly increased (p<0.01 for both). CONCLUSIONS. Whole blood thromboelastometry is able to detect a significant and reversible activation of haemostasis under hypobaric hypoxia exposure at extreme altitude (5400 m) with the characteristics of thrombin activation and independent from haematocrit changes, whereas no changes were detected at 3300 m. Present findings are of special interest resulting from the integrated effects of the different components (plasmatic factors, platelets, leukocytes and red blood cells), involved in clot formation and lysis, and may have clinical implications for patients affected by diseases associated with chronic hypoxemia.