Effects of Repeated Bouts of Exercise on the Hemostatic System

Lisa N. van der Vorm; Dana Huskens; Cécile H. Kicken; Jasper A. Remijn; Mark Roest; Bas de Laat; Adam Miszta

doi:10.1055/s-0038-1673619

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2018; 44(08): 710-722
DOI: 10.1055/s-0038-1673619

Review Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Repeated Bouts of Exercise on the Hemostatic System

Lisa N. van der Vorm

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

³Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands

,

Dana Huskens

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

,

Cécile H. Kicken

²Synapse Research Institute, Maastricht, The Netherlands

⁴Department of Anaesthesiology, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

,

Jasper A. Remijn

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

³Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands

,

Mark Roest

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

,

Bas de Laat

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

³Department of Clinical Chemistry and Hematology, Gelre Hospitals, Apeldoorn, The Netherlands

,

Adam Miszta

¹Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht University, Maastricht, The Netherlands

²Synapse Research Institute, Maastricht, The Netherlands

⁵Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

› Author Affiliations

Abstract

Physical activity is beneficial for health, for example, by lowering the risk of cardiovascular events. However, vigorous exercise is associated with the occurrence of thromboembolic events and sudden cardiac death, in particular in untrained individuals. Whereas acute exercise is known to cause a hypercoagulable state, repeated exposure to (strenuous) exercise by means of training may actually condition the hemostatic response to exercise. To date, the effects of exercise training on blood coagulability and the underlying mechanisms have yet to be fully discerned. In this review, the authors provide an overview of existing literature on how training programs and training status influence hemostasis in healthy individuals. Furthermore, they present data of a pilot study in which we studied the effects of repetitive submaximal intensity cycling on procoagulant and anticoagulant processes. It is known that factor VIII (FVIII) and von Willebrand factor (VWF) increase after exercise, but we found that this increase in FVIII and VWF (antigen, propeptide, and VWF in active conformation) was smaller on each of three subsequent days, suggesting either adaptation of endothelial activation or exhaustion of endothelial VWF supplies. With respect to thrombin generation, elevated FVIII significantly increased the thrombin generation peak but not the endogenous thrombin potential. In contrast, platelet activation in terms of P-selectin expression after stimulation with protease-activated receptor-1 and glycoprotein VI agonists decreased after exercise and did not recover, indicating exhaustion of the platelet response to repetitive exercise.

Keywords

physical training - repetitive exercise - hemostasis - coagulation - fibrinolysis

Full Text

References

References
1 World Health Organization (WHO) fact sheet cardiovascular disease. Available at: http://www.who.int/mediacentre/factsheets/fs317/en/ . Accessed March 28, 2017
2 Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation 2010; 122 (07) 743-752
3 Lavie CJ, Thomas RJ, Squires RW, Allison TG, Milani RV. Exercise training and cardiac rehabilitation in primary and secondary prevention of coronary heart disease. Mayo Clin Proc 2009; 84 (04) 373-383
4 Pollock ML, Franklin BA, Balady GJ. , et al. AHA Science Advisory. Resistance exercise in individuals with and without cardiovascular disease: benefits, rationale, safety, and prescription: an advisory from the Committee on Exercise, Rehabilitation, and Prevention, Council on Clinical Cardiology, American Heart Association; Position paper endorsed by the American College of Sports Medicine. Circulation 2000; 101 (07) 828-833
5 Swift DL, Lavie CJ, Johannsen NM. , et al. Physical activity, cardiorespiratory fitness, and exercise training in primary and secondary coronary prevention. Circ J 2013; 77 (02) 281-292
6 Kopperstad Ø, Skogen JC, Sivertsen B, Tell GS, Sæther SM. Physical activity is independently associated with reduced mortality: 15-years follow-up of the Hordaland Health Study (HUSK). PLoS One 2017; 12 (03) e0172932
7 Lippi G, Schena F, Salvagno GL, Montagnana M, Ballestrieri F, Guidi GC. Comparison of the lipid profile and lipoprotein(a) between sedentary and highly trained subjects. Clin Chem Lab Med 2006; 44 (03) 322-326
8 Swift DL, Johannsen NM, Lavie CJ, Earnest CP, Church TS. The role of exercise and physical activity in weight loss and maintenance. Prog Cardiovasc Dis 2014; 56 (04) 441-447
9 Little JP, Francois ME. High-intensity interval training for improving postprandial hyperglycemia. Res Q Exerc Sport 2014; 85 (04) 451-456
10 Thijssen DH, Tinken TM, Hopkins N, Dawson EA, Cable NT, Green DJ. The impact of exercise training on the diameter dilator response to forearm ischaemia in healthy men. Acta Physiol (Oxf) 2011; 201 (04) 427-434
11 Maron BJ. The paradox of exercise. N Engl J Med 2000; 343 (19) 1409-1411
12 Parto P, O'Keefe JH, Lavie CJ. The exercise rehabilitation paradox: less may be more?. Ochsner J 2016; 16 (03) 297-303
13 Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE. Triggering of sudden death from cardiac causes by vigorous exertion. N Engl J Med 2000; 343 (19) 1355-1361
14 Lippi G, Maffulli N. Biological influence of physical exercise on hemostasis. Semin Thromb Hemost 2009; 35 (03) 269-276
15 Schmied C, Borjesson M. Sudden cardiac death in athletes. J Intern Med 2014; 275 (02) 93-103
16 Thompson PD, Franklin BA, Balady GJ. , et al; American Heart Association Council on Nutrition, Physical Activity, and Metabolism; American Heart Association Council on Clinical Cardiology; American College of Sports Medicine. Exercise and acute cardiovascular events placing the risks into perspective: a scientific statement from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism and the Council on Clinical Cardiology. Circulation 2007; 115 (17) 2358-2368
17 Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med 2011; 364 (18) 1746-1760
18 Hilberg T, Prasa D, Stürzebecher J, Gläser D, Gabriel HHW. Thrombin potential and thrombin generation after exhaustive exercise. Int J Sports Med 2002; 23 (07) 500-504
19 Gunga HC, Kirsch K, Beneke R. , et al. Markers of coagulation, fibrinolysis and angiogenesis after strenuous short-term exercise (Wingate-test) in male subjects of varying fitness levels. Int J Sports Med 2002; 23 (07) 495-499
20 Sedgwick MJ, Thompson M, Garnham J. , et al. Acute high-intensity interval rowing increases thrombin generation in healthy men. Eur J Appl Physiol 2016; 116 (06) 1139-1148
21 Hilberg T, Prasa D, Stürzebecher J, Gläser D, Schneider K, Gabriel HH. Blood coagulation and fibrinolysis after extreme short-term exercise. Thromb Res 2003; 109 (5-6): 271-277
22 Weiss C, Bierhaus A, Kinscherf R. , et al. Tissue factor-dependent pathway is not involved in exercise-induced formation of thrombin and fibrin. J Appl Physiol (1985) 2002; 92 (01) 211-218
23 Posthuma JJ, van der Meijden PE, Ten Cate H, Spronk HM. Short- and long-term exercise induced alterations in haemostasis: a review of the literature. Blood Rev 2015; 29 (03) 171-178
24 Zadow EK, Kitic CM, Wu SSX, Fell JW, Adams MJ. Time of day and short-duration high-intensity exercise influences on coagulation and fibrinolysis. Eur J Sport Sci 2018; 18 (03) 367-375
25 Menzel K, Hilberg T. Blood coagulation and fibrinolysis in healthy, untrained subjects: effects of different exercise intensities controlled by individual anaerobic threshold. Eur J Appl Physiol 2011; 111 (02) 253-260
26 Wang JS. Exercise prescription and thrombogenesis. J Biomed Sci 2006; 13 (06) 753-761
27 Siscovick DS, Weiss NS, Fletcher RH, Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984; 311 (14) 874-877
28 Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen HI. Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation 1994; 90 (06) 2877-2885
29 Eijsvogels TM, George KP, Thompson PD. Cardiovascular benefits and risks across the physical activity continuum. Curr Opin Cardiol 2016; 31 (05) 566-571
30 El-Sayed MS, El-Sayed Ali Z, Ahmadizad S. Exercise and training effects on blood haemostasis in health and disease: an update. Sports Med 2004; 34 (03) 181-200
31 Stewart KJ. Exercise training and the cardiovascular consequences of type 2 diabetes and hypertension: plausible mechanisms for improving cardiovascular health. JAMA 2002; 288 (13) 1622-1631
32 Yoshikawa D, Ishii H, Kurebayashi N. , et al. Association of cardiorespiratory fitness with characteristics of coronary plaque: assessment using integrated backscatter intravascular ultrasound and optical coherence tomography. Int J Cardiol 2013; 162 (02) 123-128
33 Blair SN, Kohl III HW, Barlow CE, Paffenbarger Jr RS, Gibbons LW, Macera CA. Changes in physical fitness and all-cause mortality. A prospective study of healthy and unhealthy men. JAMA 1995; 273 (14) 1093-1098
34 Kokkinos P, Myers J, Faselis C. , et al. Exercise capacity and mortality in older men: a 20-year follow-up study. Circulation 2010; 122 (08) 790-797
35 Gunzer W, Konrad M, Pail E. Exercise-induced immunodepression in endurance athletes and nutritional intervention with carbohydrate, protein and fat-what is possible, what is not?. Nutrients 2012; 4 (09) 1187-1212
36 Rowbottom DG, Green KJ. Acute exercise effects on the immune system. Med Sci Sports Exerc 2000; 32 (7, Suppl): S396-S405
37 Gleeson M. Immune function in sport and exercise. J Appl Physiol (1985) 2007; 103 (02) 693-699
38 Catanho da Silva FO, Macedo DV. Physical exercise, inflammatory process and adaptive condition: an overview. Braz J Kinanthropomet Hum Performance. 2011; 13 (04) 320-328
39 Suzuki K, Naganuma S, Totsuka M. , et al. Effects of exhaustive endurance exercise and its one-week daily repetition on neutrophil count and functional status in untrained men. Int J Sports Med 1996; 17 (03) 205-212
40 Olgun N, Uysal KM, Irken G. , et al. Platelet activation in congenital heart diseases. Acta Paediatr Jpn 1997; 39 (05) 566-569
41 Wu KK. Hemostatic tests in the prediction of atherothrombotic disease. Int J Clin Lab Res 1997; 27 (03) 145-152
42 Davis RB, Boyd DG, McKinney ME, Jones CC. Effects of exercise and exercise conditioning on blood platelet function. Med Sci Sports Exerc 1990; 22 (01) 49-53
43 Kestin AS, Ellis PA, Barnard MR, Errichetti A, Rosner BA, Michelson AD. Effect of strenuous exercise on platelet activation state and reactivity. Circulation 1993; 88 (4 Pt 1): 1502-1511
44 Wang JS, Jen CJ, Chen HI. Effects of exercise training and deconditioning on platelet function in men. Arterioscler Thromb Vasc Biol 1995; 15 (10) 1668-1674
45 Ponjee GA, Janssen GM, van Wersch JW. Prolonged endurance exercise and blood coagulation: a 9 month prospective study. Blood Coagul Fibrinolysis 1993; 4 (01) 21-25
46 Gonzales F, Mañas M, Seiquer I. , et al. Blood platelet function in healthy individuals of different ages. Effects of exercise and exercise conditioning. J Sports Med Phys Fitness 1996; 36 (02) 112-116
47 Creighton BC, Kupchak BR, Aristizabal JC. , et al. Influence of training on markers of platelet activation in response to a bout of heavy resistance exercise. Eur J Appl Physiol 2013; 113 (09) 2203-2209
48 Murakami T, Komiyama Y, Masuda M. , et al. Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery disease. Eur J Clin Invest 1996; 26 (11) 996-1003
49 Roest M, van Holten TC, Fleurke GJ, Remijn JA. Platelet activation test in unprocessed blood (Pac-t-UB) to monitor platelet concentrates and whole blood of thrombocytopenic patients. Transfus Med Hemother 2013; 40 (02) 117-125
50 Ferguson EW, Bernier LL, Banta GR, Yu-Yahiro J, Schoomaker EB. Effects of exercise and conditioning on clotting and fibrinolytic activity in men. J Appl Physiol (1985) 1987; 62 (04) 1416-1421
51 Watts EJ. Haemostatic changes in long-distance runners and their relevance to the prevention of ischaemic heart disease. Blood Coagul Fibrinolysis 1991; 2 (02) 221-225
52 El-Sayed MS, Lin X, Rattu AJ. Blood coagulation and fibrinolysis at rest and in response to maximal exercise before and after a physical conditioning programme. Blood Coagul Fibrinolysis 1995; 6 (08) 747-752
53 Korsan-Bengtsen K, Wilhelmsen L, Tibblin G. Blood coagulation and fibrinolysis in relation to degree of physical activity during work and leisure time. A study based on a random sample of 54-year-old men. Acta Med Scand 1973; 193 (1-2): 73-77
54 Hilberg T, Menzel K, Wehmeier UF. Endurance training modifies exercise-induced activation of blood coagulation: RCT. Eur J Appl Physiol 2013; 113 (06) 1423-1430
55 Kupchak BR, Creighton BC, Aristizabal JC. , et al. Beneficial effects of habitual resistance exercise training on coagulation and fibrinolytic responses. Thromb Res 2013; 131 (06) e227-e234
56 Wagner DD. Cell biology of von Willebrand factor. Annu Rev Cell Biol 1990; 6: 217-246
57 Spiel AO, Gilbert JC, Jilma B. von Willebrand factor in cardiovascular disease: focus on acute coronary syndromes. Circulation 2008; 117 (11) 1449-1459
58 Pinsky DJ, Naka Y, Liao H. , et al. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97 (02) 493-500
59 El-Sayed MS, Sale C, Jones PG, Chester M. Blood hemostasis in exercise and training. Med Sci Sports Exerc 2000; 32 (05) 918-925
60 van Loon JE, Sonneveld MA, Praet SF, de Maat MP, Leebeek FW. Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise. PLoS One 2014; 9 (03) e91687
61 Stakiw J, Bowman M, Hegadorn C. , et al. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease. J Thromb Haemost 2008; 6 (01) 90-96
62 van Mourik JA, Boertjes R, Huisveld IA. , et al. von Willebrand factor propeptide in vascular disorders: a tool to distinguish between acute and chronic endothelial cell perturbation. Blood 1999; 94 (01) 179-185
63 Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 2004; 561 (Pt 1): 1-25
64 Lippi G, Salvagno GL, Montagana M, Guidi GC. Chronic influence of vigorous aerobic training on hemostasis. Blood Coagul Fibrinolysis 2005; 16 (07) 533-534
65 Wang JS, Li YS, Chen JC, Chen YW. Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arterioscler Thromb Vasc Biol 2005; 25 (02) 454-460
66 von Känel R, Dimsdale JE. Effects of sympathetic activation by adrenergic infusions on hemostasis in vivo. Eur J Haematol 2000; 65 (06) 357-369
67 Sadler JE. Low von Willebrand factor: sometimes a risk factor and sometimes a disease. Hematology (Am Soc Hematol Educ Program) 2009; 106-112
68 Goto S, Ikeda Y, Murata M. , et al. Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation. Circulation 1992; 86 (06) 1859-1863
69 Tomasiak M, Stelmach H, Rusak T, Ciborowski M, Radziwon P. Vasopressin acts on platelets to generate procoagulant activity. Blood Coagul Fibrinolysis 2008; 19 (07) 615-624
70 Delp MD, O'Leary DS. Integrative control of the skeletal muscle microcirculation in the maintenance of arterial pressure during exercise. J Appl Physiol (1985) 2004; 97 (03) 1112-1118
71 Small M, Tweddel AC, Rankin AC, Lowe GD, Prentice CR, Forbes CD. Blood coagulation and platelet function following maximal exercise: effects of beta-adrenoceptor blockade. Haemostasis 1984; 14 (03) 262-268
72 Huizinga EG, Tsuji S, Romijn RA. , et al. Structures of glycoprotein Ibalpha and its complex with von Willebrand factor A1 domain. Science 2002; 297 (5584): 1176-1179
73 Ruggeri ZM. The role of von Willebrand factor in thrombus formation. Thromb Res 2007; 120 (Suppl. 01) S5-S9
74 Savage B, Saldívar E, Ruggeri ZM. Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor. Cell 1996; 84 (02) 289-297
75 Mazzeo RS. Catecholamine responses to acute and chronic exercise. Med Sci Sports Exerc 1991; 23 (07) 839-845
76 Boman K, Hellsten G, Bruce A, Hallmans G, Nilsson TK. Endurance physical activity, diet and fibrinolysis. Atherosclerosis 1994; 106 (01) 65-74
77 Rankinen T, Rauramaa R, Vaisanen S, Halonen P, Penttila IM. Blood coagulation and fibrinolytic factors are unchanged by aerobic exercise or fat modified diet. Fibrinolysis 1994; 8: 48-53
78 van den Burg PJ, Hospers JE, van Vliet M, Mosterd WL, Bouma BN, Huisveld IA. Effect of endurance training and seasonal fluctuation on coagulation and fibrinolysis in young sedentary men. J Appl Physiol (1985) 1997; 82 (02) 613-620
79 Lockard MM, Gopinathannair R, Paton CM, Phares DA, Hagberg JM. Exercise training-induced changes in coagulation factors in older adults. Med Sci Sports Exerc 2007; 39 (04) 587-592
80 Womack CJ, Nagelkirk PR, Coughlin AM. Exercise-induced changes in coagulation and fibrinolysis in healthy populations and patients with cardiovascular disease. Sports Med 2003; 33 (11) 795-807
81 Hegde SS, Goldfarb AH, Hegde S. Clotting and fibrinolytic activity change during the 1 h after a submaximal run. Med Sci Sports Exerc 2001; 33 (06) 887-892
82 Posthuma JJ, Loeffen R, van Oerle R. , et al. Long-term strenuous exercise induces a hypercoagulable state through contact activation. Thromb Haemost 2014; 111 (06) 1197-1199
83 Hemker HC, Giesen P, Al Dieri R. , et al. Calibrated automated thrombin generation measurement in clotting plasma. Pathophysiol Haemost Thromb 2003; 33 (01) 4-15
84 Szymanski LM, Pate RR, Durstine JL. Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men. J Appl Physiol (1985) 1994; 77 (05) 2305-2310
85 Stratton JR, Chandler WL, Schwartz RS. , et al. Effects of physical conditioning on fibrinolytic variables and fibrinogen in young and old healthy adults. Circulation 1991; 83 (05) 1692-1697
86 Mosesson MW, Siebenlist KR, Meh DA. The structure and biological features of fibrinogen and fibrin. Ann N Y Acad Sci 2001; 936: 11-30
87 Ribeiro J, Almeida-Dias A, Ascensão A. , et al. Hemostatic response to acute physical exercise in healthy adolescents. J Sci Med Sport 2007; 10 (03) 164-169
88 Smith JE. Effects of strenuous exercise on haemostasis. Br J Sports Med 2003; 37 (05) 433-435
89 Szymanski LM, Pate RR. Effects of exercise intensity, duration, and time of day on fibrinolytic activity in physically active men. Med Sci Sports Exerc 1994; 26 (09) 1102-1108
90 El-Sayed MS. Effects of high and low intensity aerobic conditioning programs on blood fibrinolysis and lipid profile. Blood Coagul Fibrinolysis 1996; 7 (04) 484-490
91 El-Sayed MS. Effects of exercise on blood coagulation, fibrinolysis and platelet aggregation. Sports Med 1996; 22 (05) 282-298
92 Schuit AJ, Schouten EG, Kluft C, de Maat M, Menheere PP, Kok FJ. Effect of strenuous exercise on fibrinogen and fibrinolysis in healthy elderly men and women. Thromb Haemost 1997; 78 (02) 845-851
93 DeSouza CA, Jones PP, Seals DR. Physical activity status and adverse age-related differences in coagulation and fibrinolytic factors in women. Arterioscler Thromb Vasc Biol 1998; 18 (03) 362-368
94 Leon AS, Myers MJ, Connett J. Leisure time physical activity and the 16-year risks of mortality from coronary heart disease and all-causes in the Multiple Risk Factor Intervention Trial (MRFIT). Int J Sports Med 1997; 18 (Suppl. 03) S208-S215
95 McMurray RG, Ainsworth BE, Harrell JS, Griggs TR, Williams OD. Is physical activity or aerobic power more influential on reducing cardiovascular disease risk factors?. Med Sci Sports Exerc 1998; 30 (10) 1521-1529
96 Shaper AG, Wannamethee G, Weatherall R. Physical activity and ischaemic heart disease in middle-aged British men. Br Heart J 1991; 66 (05) 384-394
97 Biggs R, MacFarlane RG, Pilling J. Observations on fibrinolysis; experimental activity produced by exercise or adrenaline. Lancet 1947; 1 (6448): 402-405
98 Hansen JB, Wilsgård L, Olsen JO, Osterud B. Formation and persistence of procoagulant and fibrinolytic activities in circulation after strenuous physical exercise. Thromb Haemost 1990; 64 (03) 385-389
99 Röcker L, Taenzer M, Drygas WK, Lill H, Heyduck B, Altenkirch HU. Effect of prolonged physical exercise on the fibrinolytic system. Eur J Appl Physiol Occup Physiol 1990; 60 (06) 478-481
100 De Paz JA, Lasierra J, Villa JG, Viladés E, Martín-Nuño MA, González-Gallego J. Changes in the fibrinolytic system associated with physical conditioning. Eur J Appl Physiol Occup Physiol 1992; 65 (05) 388-393
101 de Geus EJ, Kluft C, de Bart AC, van Doornen LJ. Effects of exercise training on plasminogen activator inhibitor activity. Med Sci Sports Exerc 1992; 24 (11) 1210-1219
102 Gris JC, Schved JF, Feugeas O. , et al. Impact of smoking, physical training and weight reduction on FVII, PAI-1 and hemostatic markers in sedentary men. Thromb Haemost 1990; 64 (04) 516-520
103 Speiser W, Langer W, Pschaick A. , et al. Increased blood fibrinolytic activity after physical exercise: comparative study in individuals with different sporting activities and in patients after myocardial infarction taking part in a rehabilitation sports program. Thromb Res 1988; 51 (05) 543-555
104 Estellés A, Aznar J, Tormo G, Sapena P, Tormo V, España F. Influence of a rehabilitation sports programme on the fibrinolytic activity of patients after myocardial infarction. Thromb Res 1989; 55 (02) 203-212
105 Aird WC. Spatial and temporal dynamics of the endothelium. J Thromb Haemost 2005; 3 (07) 1392-1406
106 de Boer A, Kluft C, Kroon JM. , et al. Liver blood flow as a major determinant of the clearance of recombinant human tissue-type plasminogen activator. Thromb Haemost 1992; 67 (01) 83-87
107 Chandler WL, Levy WC, Veith RC, Stratton JR. A kinetic model of the circulatory regulation of tissue plasminogen activator during exercise, epinephrine infusion, and endurance training. Blood 1993; 81 (12) 3293-3302
108 Santilli F, Vazzana N, Iodice P. , et al. Effects of high-amount-high-intensity exercise on in vivo platelet activation: modulation by lipid peroxidation and AGE/RAGE axis. Thromb Haemost 2013; 110 (06) 1232-1240
109 Nofer JR, Walter M, Kehrel B. , et al. HDL3-mediated inhibition of thrombin-induced platelet aggregation and fibrinogen binding occurs via decreased production of phosphoinositide-derived second messengers 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate. Arterioscler Thromb Vasc Biol 1998; 18 (06) 861-869
110 Barlow CE, Defina LF, Radford NB. , et al. Cardiorespiratory fitness and long-term survival in “low-risk” adults. J Am Heart Assoc 2012; 1 (04) e001354
111 Kjaer M, Secher NH, Galbo H. Physical stress and catecholamine release. Baillieres Clin Endocrinol Metab 1987; 1 (02) 279-298
112 Cadroy Y, Pillard F, Sakariassen KS, Thalamas C, Boneu B, Riviere D. Strenuous but not moderate exercise increases the thrombotic tendency in healthy sedentary male volunteers. J Appl Physiol (1985) 2002; 93 (03) 829-833
113 Chen YW, Apostolakis S, Lip GY. Exercise-induced changes in inflammatory processes: implications for thrombogenesis in cardiovascular disease. Ann Med 2014; 46 (07) 439-455
114 Kargotich S, Goodman C, Keast D, Morton AR. The influence of exercise-induced plasma volume changes on the interpretation of biochemical parameters used for monitoring exercise, training and sport. Sports Med 1998; 26 (02) 101-117
115 Andrew M, Carter C, O'Brodovich H, Heigenhauser G. Increases in factor VIII complex and fibrinolytic activity are dependent on exercise intensity. J Appl Physiol (1985) 1986; 60 (06) 1917-1922
116 Cohen RJ, Epstein SE, Cohen LS, Dennis LH. Alterations of fibrinolysis and blood coagulation induced by exercise, and the role of beta-adrenergic-receptor stimulation. Lancet 1968; 2 (7581): 1264-1266
117 Iatridis SG, Ferguson JH. Effect of physical exercise on blood clotting and fibrinolysis. J Appl Physiol 1963; 18: 337-344
118 Bourey RE, Santoro SA. Interactions of exercise, coagulation, platelets, and fibrinolysis--a brief review. Med Sci Sports Exerc 1988; 20 (05) 439-446
119 Gawel MJ, Glover V, Burkitt M, Sandler M, Rose FC. The specific activity of platelet monoamine oxidase varies with platelet count during severe exercise and noradrenaline infusion. Psychopharmacology (Berl) 1981; 72 (03) 275-277
120 Haber P, Silberbauer K, Sinzinger H. Quantitative studies on reversible thrombocyte aggregation during exertion [in German]. Schweiz Med Wochenschr 1980; 110 (41) 1488-1491
121 Rakobowchuk M, McGowan CL, de Groot PC, Hartman JW, Phillips SM, MacDonald MJ. Endothelial function of young healthy males following whole body resistance training. J Appl Physiol (1985) 2005; 98 (06) 2185-2190
122 Hilberg T, Nowacki PE, Müller-Berghaus G, Gabriel HH. Changes in blood coagulation and fibrinolysis associated with maximal exercise and physical conditioning in women taking low dose oral contraceptives. J Sci Med Sport 2000; 3 (04) 383-390
123 Kahraman S, Bediz CS, Pişkin O. , et al. The effect of the acute submaximal exercise on thrombin activatable fibrinolysis inhibitor levels in young sedentary males. Clin Appl Thromb Hemost 2011; 17 (04) 414-420
124 Sand KL, Flatebo T, Andersen MB, Maghazachi AA. Effects of exercise on leukocytosis and blood hemostasis in 800 healthy young females and males. World J Exp Med 2013; 3 (01) 11-20
125 Kulaputana O, Macko RF, Ghiu I, Phares DA, Goldberg AP, Hagberg JM. Human gender differences in fibrinolytic responses to exercise training and their determinants. Exp Physiol 2005; 90 (06) 881-887
126 Ninivaggi M, de Laat M, Lancé MM. , et al. Hypoxia induces a prothrombotic state independently of the physical activity. PLoS One 2015; 10 (10) e0141797
127 Huskens D, Roest M, Remijn JA. , et al. Strenuous exercise induces a hyperreactive rebalanced haemostatic state that is more pronounced in men. Thromb Haemost 2016; 115 (06) 1109-1119
128 Bloemen S, Huskens D, Konings J. , et al. Interindividual variability and normal ranges of whole blood and plasma thrombin generation. J Appl Laboratory Med 2017; 2 (02) 150-164
129 Huskens D, Sang Y, Konings J. , et al. Standardization and reference ranges for whole blood platelet function measurements using a flow cytometric platelet activation test. PLoS One 2018; 13 (02) e0192079
130 Hulstein JJ, de Groot PG, Silence K, Veyradier A, Fijnheer R, Lenting PJ. A novel nanobody that detects the gain-of-function phenotype of von Willebrand factor in ADAMTS13 deficiency and von Willebrand disease type 2B. Blood 2005; 106 (09) 3035-3042
131 Cimenti C, Schlagenhauf A, Leschnik B. , et al. Low endogenous thrombin potential in trained subjects. Thromb Res 2013; 131 (06) e281-e285