Exercise in the Fight Against Thrombosis: Friend or Foe?

ABSTRACT

Thrombosis is a major cause of morbidity and mortality in Western countries and is associated with a range of chronic diseases such as cardiovascular disease, renal disease, diabetes, and various autoimmune conditions. Improved health care and approaches to the treatment of disease are leading to aging populations that will probably result in an increase in the incidence of thrombosis and associated manifestations over the next few decades. Adopting a physically active lifestyle through regular exercise has been proposed to lower the risk of developing thrombosis. Indeed, it has been demonstrated that exercise is beneficial for health, although there is inconsistent data from studies investigating the effect of exercise on the risk of thrombosis, with reports of both increased and decreased risk across a variety of cohorts. Studies in this area are difficult to critique due to the variety of confounders such as age, body composition, fitness level, underlying disease and treatment, as well as exercise intensity, frequency, duration, and energy expenditure. In younger individuals and those with chronic conditions such as cardiovascular and kidney disease, there is evidence that physical activity is beneficial for the lowering of thrombotic risk, whereas in older individuals the risk is more likely to be unchanged or increased. This review will explore whether exercise is a “friend” or “foe” in lowering the risk of thrombosis. It will also discuss whether elite athletes have a lower risk of thrombosis and whether exercise may help to reduce thrombotic risk in individuals with chronic disease.

Exercise - hemostasis - thrombosis - cardiovascular disease - kidney disease

REFERENCES

• 1 Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d'Etude de la Thrombose de Bretagne Occidentale.  Thromb Haemost. 2000;  83 657-660
• 2 Cushman M, Tsai A W, White R H et al.. Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.  Am J Med. 2004;  117 19-25
• 3 White R H. The epidemiology of venous thromboembolism.  Circulation. 2003;  107(23, Suppl 1) I4-I8
• 4 Kahn S R, Shrier I, Kearon C. Physical activity in patients with deep venous thrombosis: a systematic review.  Thromb Res. 2008;  122 763-773
• 5 Lee I M, Sesso H D, Oguma Y, Paffenbarger Jr R S. Relative intensity of physical activity and risk of coronary heart disease.  Circulation. 2003;  107 1110-1116
• 6 Sofi F, Capalbo A, Cesari F, Abbate R, Gensini G F. Physical activity during leisure time and primary prevention of coronary heart disease: an updated meta-analysis of cohort studies.  Eur J Cardiovasc Prev Rehabil. 2008;  15 247-257
• 7 Lippi G, Maffulli N. Biological influence of physical exercise on hemostasis.  Semin Thromb Hemost. 2009;  35 269-276
• 8 Glynn R J, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism.  Am J Epidemiol. 2005;  162 975-982
• 9 Tsai A W, Cushman M, Rosamond W D, Heckbert S R, Polak J F, Folsom A R. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.  Arch Intern Med. 2002;  162 1182-1189
• 10 van Stralen K J, Blom J W, Doggen C J, Rosendaal F R. Strenuous sport activities involving the upper extremities increase the risk of venous thrombosis of the arm.  J Thromb Haemost. 2005;  3 2110-2111
• 11 van Stralen K J, Le Cessie S, Rosendaal F R, Doggen C J. Regular sports activities decrease the risk of venous thrombosis.  J Thromb Haemost. 2007;  5 2186-2192
• 12 Sidney S, Petitti D B, Soff G A, Cundiff D L, Tolan K K, Quesenberry Jr C P. Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives.  Contraception. 2004;  70 3-10
• 13 van Stralen K J, Doggen C J, Lumley T et al.. The relationship between exercise and risk of venous thrombosis in elderly people.  J Am Geriatr Soc. 2008;  56 517-522
• 14 Peat E, Dawson M, McKenzie A, Hillis W S. The effects of acute dynamic exercise on haemostasis in 1st class Scottish football referees.  Br J Sports Med. 2008;  , November 19 (Epub ahead of print)
• 15 Jones B H, Cowan D N, Knapik J J. Exercise, training and injuries.  Sports Med. 1994;  18 202-214
• 16 Gearhart M M, Luchette F A, Proctor M C et al.. The risk assessment profile score identifies trauma patients at risk for deep vein thrombosis.  Surgery. 2000;  128 631-640
• 17 Engelman D T, Gabram S G, Allen L, Ens G E, Jacobs L M. Hypercoagulability following multiple trauma.  World J Surg. 1996;  20 5-10
• 18 Bennell K, Matheson G, Meeuwisse W, Brukner P. Risk factors for stress fractures.  Sports Med. 1999;  28 91-122
• 19 Kujala U M, Sarna S, Kaprio J. Cumulative incidence of achilles tendon rupture and tendinopathy in male former elite athletes.  Clin J Sport Med. 2005;  15 133-135
• 20 Meeusen R, Duclos M, Gleeson M et al.. Prevention, diagnosis and treatment of the overtraining syndrome.  Eur J Sport Sci. 2006;  6 1-14
• 21 DiFelice G S, Paletta Jr G A, Phillips B B, Wright R W. Effort thrombosis in the elite throwing athlete.  Am J Sports Med. 2002;  30 708-712
• 22 Kelman C W, Kortt M A, Becker N G et al.. Deep vein thrombosis and air travel: record linkage study.  BMJ. 2003;  327 1072
• 23 Kumar S. High altitude induced deep venous thrombosis: a study of 28 cases.  Indian J Surg. 2006;  68 84-88
• 24 Singh I, Chohan I S. Abnormalities of blood coagulation at high altitude.  Int J Biometeorol. 1972;  16 283-297
• 25 Kotwal J, Apte C V, Kotwal A, Mukherjee B, Jayaram J. High altitude: a hypercoagulable state: results of a prospective cohort study.  Thromb Res. 2007;  120 391-397
• 26 Deligiannis A, Björnstad H, Carre F ESC Study Group of Sports Cardiology et al. ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes.  Eur J Cardiovasc Prev Rehabil. 2006;  13 687-694
• 27 Lage J MM, Panizo C, Masdeu J, Rocha E. Cyclist's doping associated with cerebral sinus thrombosis.  Neurology. 2002;  58 665
• 28 Ferenchick G S. Anabolic/androgenic steroid abuse and thrombosis: is there a connection?.  Med Hypotheses. 1991;  35 27-31
• 29 van Stralen K J, Rosendaal F R, Doggen C JM. Minor injuries as a risk factor for venous thrombosis.  Arch Intern Med. 2008;  168 21-26
• 30 Waterhouse J, Reilly T, Edwards B. The stress of travel.  J Sports Sci. 2004;  22 946-965 discussion 965-966
• 31 Convertino V A. Blood volume: its adaptation to endurance training.  Med Sci Sports Exerc. 1991;  23 1338-1348
• 32 Coppola L, Grassia A, Coppola A et al.. Effects of a moderate-intensity aerobic program on blood viscosity, platelet aggregation and fibrinolytic balance in young and middle-aged sedentary subjects.  Blood Coagul Fibrinolysis. 2004;  15 31-37
• 33 Dinenno F A, Tanaka H, Monahan K D et al.. Regular endurance exercise induces expansive arterial remodelling in the trained limbs of healthy men.  J Physiol. 2001;  534(Pt 1) 287-295
• 34 Joffe H V, Goldhaber S Z. Upper-extremity deep vein thrombosis.  Circulation. 2002;  106 1874-1880
• 35 Vink A, Bender M H, Schep G et al.. Histopathological comparison between endofibrosis of the high-performance cyclist and atherosclerosis in the external iliac artery.  J Vasc Surg. 2008;  48 1458-1463
• 36 Arko F R, Harris E J, Zarins C K, Olcott IV C. Vascular complications in high-performance athletes.  J Vasc Surg. 2001;  33 935-942
• 37 Echlin P S, Upshur R EG, McKeag D B, Jayatilake H P. Traumatic deep vein thrombosis in a soccer player: a case study.  Thromb J. 2004;  2 8
• 38 Ehsan O, Darwish A, Edmundson C, Mills V, Al-Khaffaf H. Non-traumatic lower limb vascular complications in endurance athletes. Review of literature.  Eur J Vasc Endovasc Surg. 2004;  28 1-8
• 39 Kommareddy A, Zaroukian M H, Hassouna H I. Upper extremity deep venous thrombosis.  Semin Thromb Hemost. 2002;  28 89-99
• 40 Lippi G, Franchini M, Guidi G C. Prohibition of artificial hypoxic environments in sports: health risks rather than ethics.  Appl Physiol Nutr Metab. 2007;  32 1206-1207 discussion 1208-1209
• 41 Prandoni P. Acquired risk factors of venous thromboembolism in medical patients.  Pathophysiol Haemost Thromb. 2006;  35 128-132
• 42 Varlet-Marie E, Gaudard A, Mercier J, Bressolle F, Brun J F. Is the feeling of heavy legs in overtrained athletes related to impaired hemorheology?.  Clin Hemorheol Microcirc. 2003;  28 151-159
• 43 El-Sayed M S, El-Sayed Ali Z, Ahmadizad S. Exercise and training effects on blood haemostasis in health and disease: an update.  Sports Med. 2004;  34 181-200
• 44 Wang J S. Exercise prescription and thrombogenesis.  J Biomed Sci. 2006;  13 753-761
• 45 Lockard M M, Gopinathannair R, Paton C M, Phares D A, Hagberg J M. Exercise training-induced changes in coagulation factors in older adults.  Med Sci Sports Exerc. 2007;  39 587-592
• 46 Wannamethee S G, Lowe G DO, Whincup P H et al.. Physical activity and hemostatic and inflammatory variables in elderly men.  Circulation. 2002;  105 1785-1790
• 47 Kesaniemi Y K, Danforth Jr E, Jensen M D et al.. Dose-response issues concerning physical activity and health: an evidence-based symposium.  Med Sci Sports Exerc. 2001;  33(6 Suppl) S351-S358
• 48 Lippi G, Montagnana M, Salvagno G L, Franchini M, Guidi G C. Comparison of platelet function between sedentary individuals and competitive athletes at rest.  Thromb J. 2006;  4 10
• 49 Lippi G, Salvagno G L, Montagana M, Guidi G C. Chronic influence of vigorous aerobic training on hemostasis.  Blood Coagul Fibrinolysis. 2005;  16 533-534
• 50 Ellis M H, Manor Y, Witz M. Risk factors and management of patients with upper limb deep vein thrombosis.  Chest. 2000;  117 43-46
• 51 Kujala U M, Sarna S, Kaprio J. Cumulative incidence of Achilles tendon rupture and tendinopathy in male former elite athletes.  Clin J Sport Med. 2005;  15 133-135
• 52 Baynard T, Jacobs H M, Kessler C M, Kanaley J A, Fernhall B. Fibrinolytic markers and vasodilatory capacity following acute exercise among men of differing training status.  Eur J Appl Physiol. 2007;  101 595-602
• 53 Ahmadizad S, El-Sayed M S. The acute effects of resistance exercise on the main determinants of blood rheology.  J Sports Sci. 2005;  23 243-249
• 54 Chung I, Goyal D, Macfadyen R J, Lip G Y. The effects of maximal treadmill graded exercise testing on haemorheological, haemodynamic and flow cytometry platelet markers in patients with systolic or diastolic heart failure.  Eur J Clin Invest. 2008;  38 150-158
• 55 deJong A T, Womack C J, Perrine J A, Franklin B A. Hemostatic responses to resistance training in patients with coronary artery disease.  J Cardiopulm Rehabil. 2006;  26 80-83
• 56 Eriksson-Berg M, Egberg N, Eksborg S, Schenck-Gustafsson K. Retained fibrinolytic response and no coagulation activation after acute physical exercise in middle-aged women with previous myocardial infarction.  Thromb Res. 2002;  105 481-486
• 57 Fernhall B, Szymanski L M, Gorman P A, Milani J, Paup D C, Kessler C M. Fibrinolytic activity is similar in physically active men with and without a history of myocardial infarction.  Arterioscler Thromb Vasc Biol. 1997;  17 1106-1113
• 58 Mustonen P, Lepäntalo M, Lassila R. Physical exertion induces thrombin formation and fibrin degradation in patients with peripheral atherosclerosis.  Arterioscler Thromb Vasc Biol. 1998;  18 244-249
• 59 Dielis A W, Smid M, Spronk H M et al.. The prothrombotic paradox of hypertension: role of the renin-angiotensin and kallikrein-kinin systems.  Hypertension. 2005;  46 1236-1242
• 60 Felmeden D C, Spencer C G, Blann A D, Beevers D G, Lip G Y. Physical activity in relation to indices of endothelial function and angiogenesis factors in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).  J Intern Med. 2003;  253 81-91
• 61 Nagashima J, Musha H, Takada H et al.. Influence of physical fitness and smoking on the coagulation system in hypertensive patients: effect on prothrombin fragment F1 + 2.  Intern Med. 2007;  46 933-936
• 62 Nagelkirk P R, Franklin B A, Coughlin A M et al.. Discordant hemodynamic and fibrinolytic adaptations following a 6-week cardiac rehabilitation program.  Prev Cardiol. 2007;  10 196-203
• 63 Sabelis L W, Senden P J, Fijnheer R et al.. Endothelial markers in chronic heart failure: training normalizes exercise-induced vWF release.  Eur J Clin Invest. 2004;  34 583-589
• 64 Selig S E, Carey M F, Menzies D G et al.. Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow.  J Card Fail. 2004;  10 21-30
• 65 Aizawa K, Petrella R J. Acute and chronic impact of dynamic exercise on arterial stiffness in older hypertensives.  Open Cardiovasc Med J. 2008;  2 3-8
• 66 Adamopoulos S, Parissis J, Kroupis C et al.. Physical training reduces peripheral markers of inflammation in patients with chronic heart failure.  Eur Heart J. 2001;  22 791-797
• 67 Hambrecht R, Gielen S, Linke A et al.. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial.  JAMA. 2000;  283 3095-3101
• 68 Maiorana A, O'Driscoll G, Dembo L et al.. Effect of aerobic and resistance exercise training on vascular function in heart failure.  Am J Physiol Heart Circ Physiol. 2000;  279 H1999-H2005
• 69 Williams A D, Carey M F, Selig S et al.. Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate—a randomized controlled trial.  J Card Fail. 2007;  13 79-85
• 70 London G M. Cardiovascular disease in chronic renal failure: pathophysiologic aspects.  Semin Dial. 2003;  16 85-94
• 71 London G M, Guerin A P, Marchais S J et al.. Cardiac and arterial interactions in end-stage renal disease.  Kidney Int. 1996;  50 600-608
• 72 London G M. Increased arterial stiffness in end-stage renal failure: why is it of interest to the clinical nephrologist?.  Nephrol Dial Transplant. 1994;  9 1709-1712
• 73 Cheung A K, Sarnak M J, Yan G HEMO Study Group et al. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study.  Kidney Int. 2004;  65 2380-2389
• 74 Schiffrin E L, Lipman M L, Mann J F. Chronic kidney disease: effects on the cardiovascular system.  Circulation. 2007;  116 85-97
• 75 Preloznik Zupan I, Sabovic M, Salobir B, Buturovic Ponikvar J. Characterization of the pro-thrombotic state in CAPD patients.  Ren Fail. 2008;  30 597-602
• 76 Undas A, Kolarz M, Kopeć G, Tracz W. Altered fibrin clot properties in patients on long-term haemodialysis: relation to cardiovascular mortality.  Nephrol Dial Transplant. 2008;  23 2010-2015
• 77 Wattanakit K, Cushman M, Stehman-Breen C, Heckbert S R, Folsom A R. Chronic kidney disease increases risk for venous thromboembolism.  J Am Soc Nephrol. 2008;  19 135-140
• 78 Adams M J, Irish A B, Watts G F, Oostryck R, Dogra G K. Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function.  Thromb Res. 2008;  123 374-380
• 79 Jiménez-Jiménez R, Cuevas M J, Almar M et al.. Eccentric training impairs NF-kappaB activation and over-expression of inflammation-related genes induced by acute eccentric exercise in the elderly.  Mech Ageing Dev. 2008;  129 313-321
• 80 Esposito K, Pontillo A, Di Palo C et al.. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial.  JAMA. 2003;  289 1799-1804
• 81 Mustata S, Chan C, Lai V, Miller J A. Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients.  J Am Soc Nephrol. 2004;  15 2713-2718
• 82 Toussaint N D, Polkinghorne K R, Kerr P G. Impact of intradialytic exercise on arterial compliance and B-type natriuretic peptide levels in hemodialysis patients.  Hemodial Int. 2008;  12 254-263
• 83 Toussaint N D, Lau K K, Strauss B J, Polkinghorne K R, Kerr P G. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease.  Nephrol Dial Transplant. 2008;  23 586-593
• 84 Pechter U, Ots M, Mesikepp S et al.. Beneficial effects of water-based exercise in patients with chronic kidney disease.  Int J Rehabil Res. 2003;  26 153-156
• 85 Hung A M, Chertow G M, Young B S, Carey S, Johansen K L. Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis.  J Ren Nutr. 2002;  12 170-176
• 86 Castaneda C, Gordon P L, Parker R C, Uhlin K L, Roubenoff R, Levey A S. Resistance training to reduce the malnutrition-inflammation complex syndrome of chronic kidney disease.  Am J Kidney Dis. 2004;  43 607-616
• 87 Levi M, van der Poll T, Büller H R. Bidirectional relation between inflammation and coagulation.  Circulation. 2004;  109 2698-2704