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Semin Thromb Hemost 2012; 38(02): 156-163
DOI: 10.1055/s-0032-1301413
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Exposure to High Altitude: A Risk Factor for Venous Thromboembolism?

Neha Gupta
1   Genomics Division, Defence Institute of Physiology & Allied Sciences, Timarpur, Delhi, India
,
Mohammad Z. Ashraf
1   Genomics Division, Defence Institute of Physiology & Allied Sciences, Timarpur, Delhi, India
› Author Affiliations
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Publication History

Publication Date:
17 February 2012 (online)

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Abstract

There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several previous studies have suggested that conditions present at HAs contribute to establish a prothrombotic milieu, published reports are contradictory and the exact underlying mechanism remains poorly understood. Results from HA studies also show that environmental conditions at HA such as hypoxia, dehydration, hemoconcentration, low temperature, use of constrictive clothing as well as enforced stasis due to severe weather, would support the occurrence of thrombotic disorders. The three leading factors of Virchow triad, that is, venous stasis, hypercoagulability, and vessel-wall injury, all appear to be present at HA. In synthesis, the large list of environmental variables suggests that a single cause of HA-induced thromboembolic disorders (TED) may not exist, so that this peculiar phenomenon should be seen as a complex or multifactorial trait. Further investigation is needed to understand the risk of TED at HA as well as the possible underlying mechanisms.

Keywords

venous thrombosis - pulmonary embolism - high altitude - air travel - thrombosis - hypercoagulation
 

  • References

  • 1 Lippi G, Favaloro EJ, Franchini M. Coagulopathies and thrombosis: usual and unusual causes and associations, part IV. Semin Thromb Hemost 2011; 37 (3) 175-180
    Thieme ConnectPubMedSearch in Google Scholar
  • 2 Franchini M, Lippi G, Favaloro EJ. Coagulopathies and thrombosis: usual and unusual causes and associations, part I. Semin Thromb Hemost 2009; 35 (3) 257-259
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Lippi G, Franchini M, Favaloro EJ. Coagulopathies and thrombosis: usual and unusual causes and associations, part II. Semin Thromb Hemost 2009; 35 (7) 591-595
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Favaloro EJ, Lippi G, Franchini M. Coagulopathies and thrombosis: usual and unusual causes and associations, part III. Semin Thromb Hemost 2010; 36 (1) 1-5
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Coombes R. Venous thromboembolism caused 25,000 deaths a year, say MPs. BMJ 2005; 330 (7491) 559
    PubMedSearch in Google Scholar
  • 6 Lippi G, Franchini M. Pathogenesis of venous thromboembolism: when the cup runneth over. Semin Thromb Hemost 2008; 34 (8) 747-761
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Lippi G, Franchini M, Favaloro EJ. Unsuspected triggers of venous thromboembolism—trivial or not so trivial?. Semin Thromb Hemost 2009; 35 (7) 597-604
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981; 68 (5) 1370-1373
    CrossrefPubMedSearch in Google Scholar
  • 9 Koster T, Rosendaal FR, Briët E , et al. Protein C deficiency in a controlled series of unselected outpatients: an infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study). Blood 1995; 85 (10) 2756-2761
    PubMedSearch in Google Scholar
  • 10 Lensen RPM, Rosendaal FR, Koster T , et al. Apparent different thrombotic tendency in patients with factor V Leiden and protein C deficiency due to selection of patients. Blood 1996; 88 (11) 4205-4208
    PubMedSearch in Google Scholar
  • 11 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (6) 715-722
    CrossrefPubMedSearch in Google Scholar
  • 12 Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88 (10) 3698-3703
    CrossrefPubMedSearch in Google Scholar
  • 13 Bank I, Libourel EJ, Middeldorp S , et al. Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study. Arch Intern Med 2004; 164 (17) 1932-1937
    CrossrefPubMedSearch in Google Scholar
  • 14 Homans J. Thrombosis of the deep leg veins due to prolonged sitting. N Engl J Med 1954; 250 (4) 148-149
    CrossrefPubMedSearch in Google Scholar
  • 15 Gibbs NM. Venous thrombosis of the lower limbs with particular reference to bed-rest. Br J Surg 1957; 45 (191) 209-236
    CrossrefPubMedSearch in Google Scholar
  • 16 Di Fabio F, Lykoudis P, Gordon PH. Thromboembolism in inflammatory bowel disease: an insidious association requiring a high degree of vigilance. Semin Thromb Hemost 2011; 37 (3) 220-225
    Thieme ConnectPubMedSearch in Google Scholar
  • 17 Wong RC, Favaloro EJ. Clinical features, diagnosis, and management of the antiphospholipid syndrome. Semin Thromb Hemost 2008; 34 (3) 295-304
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Hull RD, Raskob GE. Prophylaxis of venous thromboembolic disease following hip and knee surgery. J Bone Joint Surg Am 1986; 68 (1) 146-150
    PubMedSearch in Google Scholar
  • 19 Franchini M, Montagnana M, Favaloro EJ, Lippi G. The bidirectional relationship of cancer and hemostasis and the potential role of anticoagulant therapy in moderating thrombosis and cancer spread. Semin Thromb Hemost 2009; 35 (7) 644-653
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Fonseca AC, Ferreira JJ, Albuquerque L, Ferro JM. Sneeze as a precipitating factor of cerebral venous thrombosis. Eur J Neurol 2007; 14 (10) e7-e8
    PubMedSearch in Google Scholar
  • 21 Röttger C, Trittmacher S, Gerriets T, Kaps M, Stolz E. Sinus thrombosis after a jump from a small rock and a sneezing attack: minor endothelial trauma as a precipitating factor for cerebral venous thrombosis?. Headache 2004; 44 (8) 812-815
    CrossrefPubMedSearch in Google Scholar
  • 22 Kakkar VV, Howe CT, Nicolaides AN, Renney JT, Clarke MB. Deep vein thrombosis of the leg. Is there a “high risk” group?. Am J Surg 1970; 120 (4) 527-530
    Search in Google Scholar
  • 23 McColl MD, Ramsay JE, Tait RC , et al. Risk factors for pregnancy associated venous thromboembolism. Thromb Haemost 1997; 78 (4) 1183-1188
    PubMedSearch in Google Scholar
  • 24 Lippi G, Franchini M, Guidi GC. Prohibition of artificial hypoxic environments in sports: health risks rather than ethics. Appl Physiol Nutr Metab 2007; 32 (6) 1206-1207, discussion 1208–1209
    CrossrefPubMedSearch in Google Scholar
  • 25 Bendz B, Rostrup M, Sevre K, Andersen TO, Sandset PM. Association between acute hypobaric hypoxia and activation of coagulation in human beings. Lancet 2000; 356 (9242) 1657-1658
    CrossrefPubMedSearch in Google Scholar
  • 26 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. JAMA 2006; 295 (19) 2251-2261
    CrossrefPubMedSearch in Google Scholar
  • 27 Anand AC, Jha SK, Saha A, Sharma V, Adya CM. Thrombosis as a complication of extended stay at high altitude. Natl Med J India 2001; 14 (4) 197-201
    PubMedSearch in Google Scholar
  • 28 Curtis R. Outdoor action guide to high altitude: acclimatization and illnesses. Outdoor Action Program. Princeton NJ; 1995 Available at: http://www.princeton.edu/~oa/safety/altitude.html . Accessed Jan 2012
    PubMed
  • 29 Hackett P, Roach R. High-altitude medicine. In: Auerbach P, ed. Wilderness Medicine. 5th ed. Philadelphia: : Mosby Elsevier; ; 2007: 1-2
    Search in Google Scholar
  • 30 Ashraf HM, Javed A, Ashraf S. Pulmonary embolism at high altitude and hyperhomocysteinemia. J Coll Physicians Surg Pak 2006; 16 (1) 71-73
    PubMedSearch in Google Scholar
  • 31 Anand AC, Saha A, Kumar R, Sharma V, Jha SK. Portal system thrombosis: a new dimension of high altitude illnesses. Trop Gastroenterol 2000; 21 (4) 172-173
    PubMedSearch in Google Scholar
  • 32 Fujimaki T, Matsutani M, Asai A, Kohno T, Koike M. Cerebral venous thrombosis due to high-altitude polycythemia. Case report. J Neurosurg 1986; 64 (1) 148-150
    CrossrefPubMedSearch in Google Scholar
  • 33 Abbasi AA, Harrop NS. An unusual swelling in the neck. Emerg Med J 2005; 22 (9) 674-675
    CrossrefPubMedSearch in Google Scholar
  • 34 Jha SK, Anand AC, Sharma V, Kumar N, Adya CM. Stroke at high altitude: Indian experience. High Alt Med Biol 2002; 3 (1) 21-27
    CrossrefPubMedSearch in Google Scholar
  • 35 Kumar S. High altitude induced deep venous thrombosis: a case study of 28 cases. Indian J Surg 2006; 68 (2) 84-88
    PubMedSearch in Google Scholar
  • 36 Bucur IJ. Venous thromboembolism at high altitude. Saudi Med J 1999; 20 (1) 56-62
    PubMedSearch in Google Scholar
  • 37 Presti B, Berthrong M, Sherwin RM. Chronic thrombosis of major pulmonary arteries. Hum Pathol 1990; 21 (6) 601-606
    CrossrefPubMedSearch in Google Scholar
  • 38 Smallman DP, McBratney CM, Olsen CH, Slogic KM, Henderson CJ. Quantification of the 5-year incidence of thromboembolic events in U.S. Air Force Academy cadets in comparison to the U.S. Naval and Military Academies. Mil Med 2011; 176 (2) 209-213
    PubMedSearch in Google Scholar
  • 39 Hussain T, Niaz A. Deep vein thrombosis at high altitude. J Pak Med Assoc 2002; 52 (9) 440
    PubMedSearch in Google Scholar
  • 40 Torgovicky R, Azaria B, Grossman A, Eliyahu U, Goldstein L. Sinus vein thrombosis following exposure to simulated high altitude. Aviat Space Environ Med 2005; 76 (2) 144-146
    PubMedSearch in Google Scholar
  • 41 Cheng S, Chng SM, Singh R. Cerebral venous infarction during a high altitude expedition. Singapore Med J 2009; 50 (8) e306-e308
    PubMedSearch in Google Scholar
  • 42 Skaiaa SC, Stave H. Recurrent sagittal sinus thrombosis occurring at high altitude during expeditions to Cho Oyu. Wilderness Environ Med 2006; 17 (2) 132-136
    CrossrefPubMedSearch in Google Scholar
  • 43 Nair V, Mohapatro AK, Sreedhar M , et al. A case of hereditary protein S deficiency presenting with cerebral sinus venous thrombosis and deep vein thrombosis at high altitude. Acta Haematol 2008; 119 (3) 158-161
    CrossrefPubMedSearch in Google Scholar
  • 44 Boulos P, Kouroukis C, Blake G. Superior sagittal sinus thrombosis occurring at high altitude associated with protein C deficiency. Acta Haematol 1999; 102 (2) 104-106
    CrossrefPubMedSearch in Google Scholar
  • 45 Jung S, Wiest R, Frigerio S, Mattle HP, Hess CW. Cerebral air embolism caused by a bronchogenic cyst. Pract Neurol 2010; 10 (3) 164-166
    CrossrefPubMedSearch in Google Scholar
  • 46 Saito S, Tanaka SK. A case of cerebral sinus thrombosis developed during a high-altitude expedition to Gasherbrum I. Wilderness Environ Med 2003; 14 (4) 226-230
    CrossrefPubMedSearch in Google Scholar
  • 47 Nayak NC, Roy S, Narayanan TK. Pathologic features of altitude sickness. Am J Pathol 1964; 45: 381-391
    PubMedSearch in Google Scholar
  • 48 Bärtsch P, Waber U, Haeberli A , et al. Enhanced fibrin formation in high-altitude pulmonary edema. J Appl Physiol 1987; 63 (2) 752-757
    PubMedSearch in Google Scholar
  • 49 Arias-Stella J, Kruger H. Pathology of high altitude pulmonary edema. Arch Pathol 1963; 76: 147-157
    PubMedSearch in Google Scholar
  • 50 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 (3) 293-300
    CrossrefPubMedSearch in Google Scholar
  • 51 Gertler JP, Perry L, L’Italien G , et al. Ambient oxygen tension modulates endothelial fibrinolysis. J Vasc Surg 1993; 18 (6) 939-945, discussion 945–946
    PubMedSearch in Google Scholar
  • 52 Chohan IS. Blood coagulation changes at high altitude. Def Sci J 1984; 34 (4) 361-379
    PubMedSearch in Google Scholar
  • 53 Andrew M, O’Brodovich H, Sutton J. Operation Everest II: coagulation system during prolonged decompression to 282 Torr. J Appl Physiol 1987; 63 (3) 1262-1267
    PubMedSearch in Google Scholar
  • 54 Bärtsch 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 (5) 2136-2144
    PubMedSearch in Google Scholar
  • 55 Mannucci PM, Gringeri A, Peyvandi F, Di Paolantonio T, Mariani G. Short-term exposure to high altitude causes coagulation activation and inhibits fibrinolysis. Thromb Haemost 2002; 87 (2) 342-343
    PubMedSearch in Google Scholar
  • 56 Crosby A, Talbot NP, Harrison P, Keeling D, Robbins PA. Relation between acute hypoxia and activation of coagulation in human beings. Lancet 2003; 361 (9376) 2207-2208
    CrossrefPubMedSearch in Google Scholar
  • 57 Kotwal J, Apte CV, Kotwal A, Mukherjee B, Jayaram J. High altitude: a hypercoagulable state: results of a prospective cohort study. Thromb Res 2007; 120 (3) 391-397
    CrossrefPubMedSearch in Google Scholar
  • 58 Nakanishi K, Tajima F, Nakata Y , et al. Hypercoagulable state in a hypobaric, hypoxic environment causes non-bacterial thrombotic endocarditis in rats. J Pathol 1997; 181 (3) 338-346
    CrossrefPubMedSearch in Google Scholar
  • 59 Gray GW, Bryan AC, Freedman MH , et al. Effect of altitude exposure on platelets. J Appl Physiol 1975; 39 (4) 648-652
    PubMedSearch in Google Scholar
  • 60 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 (3) 177-182
    CrossrefPubMedSearch in Google Scholar
  • 61 Sharma SC. Platelet count on slow induction to high altitude. Int J Biometeorol 1986; 30 (1) 27-32
    CrossrefPubMedSearch in Google Scholar
  • 62 Sharma SC. Platelet count in temporary residents of high altitude. J Appl Physiol 1980; 49 (6) 1047-1048
    PubMedSearch in Google Scholar
  • 63 Simon-Schnass I, Korniszewski L. The influence of vitamin E on rheological parameters in high altitude mountaineers. Int J Vitam Nutr Res 1990; 60 (1) 26-34
    PubMedSearch in Google Scholar
  • 64 Hartmann S, Krafft A, Huch R, Breymann C. Effect of altitude on thrombopoietin and the platelet count in healthy volunteers. Thromb Haemost 2005; 93 (1) 115-117
    PubMedSearch in Google Scholar
  • 65 Hudson JG, Bowen AL, Navia P , et al. The effect of high altitude on platelet counts, thrombopoietin and erythropoietin levels in young Bolivian airmen visiting the Andes. Int J Biometeorol 1999; 43 (2) 85-90
    CrossrefPubMedSearch in Google Scholar
  • 66 Vij AG. Effect of prolonged stay at high altitude on platelet aggregation and fibrinogen levels. Platelets 2009; 20 (6) 421-427
    CrossrefPubMedSearch in Google Scholar
  • 67 Pichler Hefti J, Risch L, Hefti U , et al. Changes of coagulation parameters during high altitude expedition. Swiss Med Wkly 2010; 140 (7-8) 111-117
    PubMedSearch in Google Scholar
  • 68 DeLoughery TG, Robertson DG, Smith CA, Sauer D. Moderate hypoxia suppresses exercise-induced procoagulant changes. Br J Haematol 2004; 125 (3) 369-372
    CrossrefPubMedSearch in Google Scholar
  • 69 Bertina RM, Koeleman BP, Koster T , et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369 (6475) 64-67
    CrossrefPubMedSearch in Google Scholar
  • 70 Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995; 346 (8983) 1133-1134
    CrossrefPubMedSearch in Google Scholar
  • 71 Iliev I. Training at altitude. In: Medicine in Sport Training and Coaching. Karvonen J, Lemon PWR, Iliev I, eds Berlin: : Basel, Karger; ; 1992: 69-103
    Search in Google Scholar
  • 72 Levine BD, Stray-Gundersen J. A practical approach to altitude training: where to live and train for optimal performance enhancement. Int J Sports Med 1992; 13 (Suppl 1) S209-S212
    Thieme ConnectPubMedSearch in Google Scholar
  • 73 Sanchis-Gomar F, Martinez-Bello VE, Domenech E , et al. Effect of intermittent hypoxia on hematological parameters after recombinant human erythropoietin administration. Eur J Appl Physiol 2009; 107 (4) 429-436
    PubMedSearch in Google Scholar
  • 74 Ekblom BT. Blood boosting and sport. Best Pract Res Clin Endocrinol Metab 2000; 14 (1) 89-98
    CrossrefPubMedSearch in Google Scholar
  • 75 Sunder-Plassmann G, Hörl WH. Effect of erythropoietin on cardiovascular diseases. Am J Kidney Dis 2001; 38 (4, Suppl 1) S20-S25
    PubMedSearch in Google Scholar
  • 76 Alhadad A, Acosta S, Sarabi L, Kölbel T. Pulmonary embolism associated with protein C deficiency and abuse of anabolic-androgen steroids. Clin Appl Thromb Hemost 2010; 16 (2) 228-231
    CrossrefPubMedSearch in Google Scholar
  • 77 Tischer KH, Heyny-von Haussen R, Mall G, Doenecke P. [Coronary thrombosis and ectasia of coronary arteries after long-term use of anabolic steroids]. Z Kardiol 2003; 92 (4) 326-331
    CrossrefPubMedSearch in Google Scholar
  • 78 Kuipers S, Schreijer AJ, Cannegieter SC, Büller HR, Rosendaal FR, Middeldorp S. Travel and venous thrombosis: a systematic review. J Intern Med 2007; 262 (6) 615-634
    CrossrefPubMedSearch in Google Scholar
  • 79 Collins RE, Field S, Castleden WM. Thrombosis of leg arteries after prolonged travel. BMJ 1979; 2 (6203) 1478
    PubMedSearch in Google Scholar
  • 80 Ferrari E, Chevallier T, Chapelier A, Baudouy M. Travel as a risk factor for venous thromboembolic disease: a case-control study. Chest 1999; 115 (2) 440-444
    CrossrefPubMedSearch in Google Scholar
  • 81 Stricker H, Colucci G, Godio M, Mossi G, Mombelli G. The influence of a prolonged sitting position on the biochemical markers of coagulation activation in healthy subjects: evidence of reduced thrombin generation. J Thromb Haemost 2003; 1 (2) 380-381
    CrossrefPubMedSearch in Google Scholar
  • 82 Wright HP, Osborn SB. Effect of posture on venous velocity, measured with 24NaCl. Br Heart J 1952; 14 (3) 325-330
    CrossrefPubMedSearch in Google Scholar
  • 83 Carruthers M, Arguelles AE, Mosovich A. Man in transit: biochemical and physiological changes during intercontinental flights. Lancet 1976; 1 (7967) 977-981
    PubMedSearch in Google Scholar
  • 84 Simons R, Krol J. Jet leg, pulmonary embolism, and hypoxia. Lancet 1996; 348 (9024) 416
    PubMedSearch in Google Scholar
  • 85 Lapostolle F, Surget V, Borron SW , et al. Severe pulmonary embolism associated with air travel. N Engl J Med 2001; 345 (11) 779-783
    CrossrefPubMedSearch in Google Scholar
  • 86 Landgraf H, Vanselow B, Schulte-Huermann D, Mülmann MV, Bergau L. Economy class syndrome: rheology, fluid balance, and lower leg edema during a simulated 12-hour long distance flight. Aviat Space Environ Med 1994; 65 (10 Pt 1) 930-935
    PubMedSearch in Google Scholar
  • 87 Moyses C, Cederholm-Williams SA, Michel CC. Haemoconcentration and accumulation of white cells in the feet during venous stasis. Int J Microcirc Clin Exp 1987; 5 (4) 311-320
    PubMedSearch in Google Scholar