Reduced coagulation at high altitude identified by thromboelastography

Daniel S. Martin; Jim S. Pate; Andre Vercueil; Patrick W. Doyle; Michael G. Mythen; Mike P. W. Grocott; for the Caudwell Xtreme Everest Research Group

doi:10.1160/TH12-01-0004

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2012; 107(06): 1066-1071
DOI: 10.1160/TH12-01-0004

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Reduced coagulation at high altitude identified by thromboelastography

Authors

Daniel S. Martin

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK

²University College London, Division of Surgery and Interventional Science, Royal Free Hospital, London, UK
Jim S. Pate

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK

³Centre for Health and Human Performance, London, UK
Andre Vercueil

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK

⁴King's College Hospital, Denmark Hill, London, UK
Patrick W. Doyle

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK

⁵Anaesthetic Department, Charing Cross Hospital, Fulham Palace Road, London, UK
Michael G. Mythen

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK
Mike P. W. Grocott

¹UCL Centre for Altitude, Space and Extreme Environment Medicine, Portex Unit, Institute of Child Health, London, UK

⁶Integrative Physiology Group, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Sir Henry Wellcome Laboratories, University Hospital Southampton NHS Foundation Trust, Southampton, UK

⁷Critical Care Research Unit, University Hospital Southampton NHS Foundation Trust, Southampton, UK

for the Caudwell Xtreme Everest Research Group

Abstract

Summary

The impact of hypoxaemia on blood coagulation remains unclear despite use of a variety of measures to address the issue. We report the first use of thromboelastography (TEG) at high altitude to describe the dynamics of clot formation in whole blood samples. Seventeen healthy volunteers ascended to 5,300 m following an identical ascent profile; TEG measurements at 4,250 m and 5,300 m were compared with those from sea level. Peripheral oxygen saturation (SpO₂) and haematocrit were also measured. Ascent resulted in a decline in SpO₂ from 97.8 (± 1.2) % at sea level to 86.9 (± 3.3) % at 4,250 m and 79.5 (± 5.8) % at 5,300 m (p<0.001); haematocrit rose from 43.7 (± 2.8) % at sea level, to 46.7 (± 3.9) % and 52.6 (± 3.2) % at 4,250 m and 5,300 m, respectively (p<0.01). TEG reaction (R)-time and kinetic (K)-time were both increased at 5,300 m compared to sea level, 8.95 (± 1.37) minutes (min) to 11.69 (± 2.91) min (p=0.016) and 2.40 (± 0.66) min to 4.99 (± 1.67) min (p<0.001), respectively. Additionally the alpha (α)- angle was decreased from 57.7 (± 8.2) to 51.6 (± 6.4) (p<0.001). There was no change in maximum amplitude (MA) on ascent to altitude. These changes are consistent with an overall pattern of slowed coagulation at high altitude.

Keywords

Altitude - hypoxia - blood coagulation - thrombelastography - blood coagulation tests

Full Text

References

References
1 Guyton AC, Hall J. Textbook of Medical Physiology. Philadelphia:: Saunders; 2006
2 Hoffman M, Monroe DM. A cell-based model of hemostasis. Thromb Haemost 2001; 85: 958-965.
3 Ansell JE. Air travel and venous thromboembolism--is the evidence in?. N Engl J Med 2001; 345: 828-829.
4 Toff WD, Jones CI, Ford I. et al. Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation. J Am Med Assoc 2006; 295: 2251-2261.
5 Schobersberger W, Mittermayr M, Fries D. et al. Changes in blood coagulation of arm and leg veins during a simulated long-haul flight. Thromb Res 2007; 119: 293-300.
6 Crosby A, Talbot N P, Harrison P. et al. Relation between acute hypoxia and activation of coagulation in human beings. Lancet 2003; 361: 2207-2208.
7 Hodkinson PD, Hunt BJ, Parmar K, Ernsting J. Is mild normobaric hypoxia a risk factor for venous thromboembolism?. J Thromb Haemost 2003; 1: 2131-2133.
8 O'Brodovich HM, Andrew M, Gray GW. et al. Hypoxia alters blood coagulation during acute decompression in humans. J Appl Physiol 1984; 56: 666-670.
9 Andrew M, O'Brodovich H, Sutton J. Operation Everest II: coagulation system during prolonged decompression to 282 Torr. J Appl Physiol 1987; 63: 1262-1267.
10 Bartsch P. How thrombogenic is hypoxia?. J Am Med Assoc 2006; 295: 2297-2299.
11 Dickinson J, Heath D, Gosney J, Williams D. Altitude-related deaths in seven trekkers in the Himalayas. Thorax 1983; 38: 646-656.
12 Mallett SV, Cox DJ. Thrombelastography. Br J Anaesth 1992; 69: 307-313.
13 Kaufmann CR, Dwyer KM, Crews JD. et al. Usefulness of thrombelastography in assessment of trauma patient coagulation. J Trauma 1997; 42: 716-722.
14 Shore-Lesserson L, Manspeizer HE, DePerio M. et al. Thromboelastography-guided transfusion algorithm reduces transfusions in complex cardiac surgery. Anesth Analg 1999; 88: 312-319.
15 Harding SA, Mallett S V, Peachey TD, Cox DJ. Use of heparinase modified thrombelastography in liver transplantation. Br J Anaesth 1997; 78: 175-179.
16 Roche AM, James MF, Bennett-Guerrero E. et al. Calcium supplementation of saline-based colloids does not produce equivalent coagulation profiles to similarly balanced salt preparations. J Cardiothorac Vasc Anesth 2006; 20: 807-811.
17 Bull BS, Koepke JA, Simson E. et al. National Committee for Clinical Laboratory Standard. Procedure for Determining Packed Cell Volume by the Microhemato-crit Method: Approved Standard. Document H7-A3. NCCLS. 2001 20. 18.
18 Martin DS, Goedhart P, Vercueil A. et al. Changes in sublingual microcirculatory flow index and vessel density on ascent to altitude. Exp Physiol 2010; 95: 880-891.
19 Roach RC, Bartsch P, Hackett PH. et al. The Lake Louise AMS scoring consensus committee. The Lake Louise acute mountain sickness scoring system. Sutton JR, Houston CS, Coates G. Hypoxia and molecular medicine. Burlington, VT: Queen City Press; 1993: 272-274.
20 Levett DZ, Martin DS, Wilson MH. et al. Design and conduct of Caudwell Xtreme Everest: an observational cohort study of variation in human adaptation to progressive environmental hypoxia. BMC Med Res Methodol 2010; 10: 98.
21 Jha SK, Anand AC, Sharma V, Kumar N, Adya CM. Stroke at high altitude: Indian experience. High Alt Med Biol 2002; 3: 21-27.
22 Tanaka KA, Key NS, Levy JH. Blood coagulation: hemostasis and thrombin regulation. Anesth Analg 2009; 108: 1433-1446.
23 Birks JW, Klassen LW, Gurney CW. Hypoxia-induced thrombocytopenia in mice. J Lab Clin Med 1975; 86: 230-238.
24 Sharma SC. Platelet count and adhesiveness on induction to high altitude by air and road. Int J Biometeorol 1982; 26: 219-224.
25 Chatterji JC, Ohri VC, Das BK. et al. Platelet count, platelet aggregation and fibrinogen levels following acute induction to high altitude (3200 and 3771 metres). Thromb Res 1982; 26: 177-182.
26 Simon-Schnass I, Korniszewski L. The influence of vitamin E on rheological parameters in high altitude mountaineers. Int J Vitam Nutr Res 1990; 60: 26-34.
27 Bartsch P, Haeberli A, Franciolli M, Kruithof EK, Straub PW. Coagulation and fibrinolysis in acute mountain sickness and beginning pulmonary edema. J Appl Physiol 1989; 66: 2136-2144.
28 Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976; 2: 1149-1155.
29 el-Sayed MS. Effects of exercise on blood coagulation, fibrinolysis and platelet aggregation. Sports Med 1996; 22: 282-298.
30 Bourey RE, Santoro SA. Interactions of exercise, coagulation, platelets, and fibrinolysis--a brief review. Med Sci Sports Exerc 1988; 20: 439-446.
31 Cunningham WL, Becker EJ, Kreuzer F. Catecholamines in plasma and urine at high altitude. J Appl Physiol 1965; 20: 607-610.
32 Ikarugi H, Taka T, Nakajima S. et al. Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans. J Appl Physiol 1999; 86: 133-138.
33 Levett DZ, Fernandez BO, Riley H. et al. The role of nitrogen oxides in human adaptation to hypoxia. Scientific Reports. 2011 1. Article 109.
34 Nielsen VG. Nitric oxide decreases coagulation protein function in rabbits as assessed by thromboelastography. Anesth Analg 2001; 92: 320-323.
35 Catani MV, Bernassola F, Rossi A. et al. Inhibition of clotting factor XIII activity by nitric oxide. Biochem Biophys Res Commun 1998; 249: 275-278.
36 Samama CM, Diaby M, Fellahi JL. et al. Inhibition of platelet aggregation by inhaled nitric oxide in patients with acute respiratory distress syndrome. Anesthesiology 1995; 83: 56-65.
37 Kettner SC, Gonano C, Seebach F. et al. Endogenous heparin-like substances significantly impair coagulation in patients undergoing orthotopic liver transplantation. Anesth Analg 1998; 86: 691-695.
38 Zuckerman L, Cohen E, Vagher J P. et al. Comparison of thrombelastography with common coagulation tests. Thromb Haemost 1981; 46: 752-756.
39 Lang T, von Depka M. Possibilities and limitations of thrombelastometry/-graphy. Hamostaseologie 2006; 26: S20-29.
40 Chen A, Teruya J. Global hemostasis testing thromboelastography: old technology, new applications. Clin Lab Med 2009; 29: 391-407.
41 Wolberg AS, Meng ZH, Monroe DMr, Hoffman M. A systematic evaluation of the effect of temperature on coagulation enzyme activity and platelet function. J Trauma 2004; 56: 1221-1228.