Semin Thromb Hemost 2018; 44(08): 787-795
DOI: 10.1055/s-0038-1675381
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Impact of Exercise on Hemophilia

Eva Zetterberg
1   Department of Translational Medicine, Malmö Centre for Thrombosis and Haemostasis, Lund University, Malmö, Sweden
,
Marcus Ljungkvist
1   Department of Translational Medicine, Malmö Centre for Thrombosis and Haemostasis, Lund University, Malmö, Sweden
,
Maryem Salim
1   Department of Translational Medicine, Malmö Centre for Thrombosis and Haemostasis, Lund University, Malmö, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2018 (online)

Abstract

Sports and strenuous exercise have traditionally been discouraged for people with hemophilia (PWH) because of the perceived risk of bleeding. In this review, studies investigating the pros and cons of exercise are presented, and although most studies are of low validity, the randomized trials that do exist tell us that PWH benefit from exercise in terms of improved muscular function, endurance, and quality of life and that increased bleeding does not seem to be an issue. The authors also review the studies that have analyzed the current physical status of PWH compared with the general population in different countries. Finally, they review the current knowledge on the effect of exercise on specific coagulation factors as well as on global coagulation and demonstrate that exercise increases factor VIII levels in healthy persons, all persons with hemophilia B (HB) and in persons with mild and moderate hemophilia A (HA). Further, the authors did not find any evidence that the global coagulation capacity, measured with thrombin generation or thromboelastographic methods, increases after exercise in severe HA or HB.

 
  • References

  • 1 Haskell WL, Lee IM, Pate RR. , et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc 2007; 39 (08) 1423-1434
  • 2 Vermunt PW, Milder IE, Wielaard F. , et al. Behavior change in a lifestyle intervention for type 2 diabetes prevention in Dutch primary care: opportunities for intervention content. BMC Fam Pract 2013; 14: 78
  • 3 Broderick JM, Guinan E, Kennedy MJ. , et al. Feasibility and efficacy of a supervised exercise intervention in de-conditioned cancer survivors during the early survivorship phase: the PEACH trial. J Cancer Surviv 2013; 7 (04) 551-562
  • 4 Pahkala K, Laitinen TT, Heinonen OJ. , et al. Association of fitness with vascular intima-media thickness and elasticity in adolescence. Pediatrics 2013; 132 (01) e77-e84
  • 5 Rongen-van Dartel SA, Repping-Wuts H, Flendrie M. , et al. Effect of aerobic exercise training on fatigue in rheumatoid arthritis: a meta-analysis. Arthritis Care Res (Hoboken) 2015; 67 (08) 1054-1062
  • 6 Brunner A, Stäuber F, Göhler S. , et al. Quadriceps strength, inter-extremity difference (IED) and joint status in adult persons with severe haemophilia in different age stages. Haemophilia 2013; 19 (02) 267-274
  • 7 Falk B, Portal S, Tiktinsky R. , et al. Bone properties and muscle strength of young haemophilia patients. Haemophilia 2005; 11 (04) 380-386
  • 8 González LM, Querol F, Gallach JE, Gomis M, Aznar VA. Force fluctuations during the Maximum Isometric Voluntary Contraction of the quadriceps femoris in haemophilic patients. Haemophilia 2007; 13 (01) 65-70
  • 9 Hilberg T, Herbsleb M, Gabriel HH, Jeschke D, Schramm W. Proprioception and isometric muscular strength in haemophilic subjects. Haemophilia 2001; 7 (06) 582-588
  • 10 Khawaji M, Astermark J, Berntorp E. Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life. Eur J Haematol 2012; 88 (04) 329-335
  • 11 Khawaji M, Akesson K, Berntorp E. Long-term prophylaxis in severe haemophilia seems to preserve bone mineral density. Haemophilia 2009; 15 (01) 261-266
  • 12 Khawaji M, Astermark J, Akesson K, Berntorp E. Physical activity for prevention of osteoporosis in patients with severe haemophilia on long-term prophylaxis. Haemophilia 2010; 16 (03) 495-501
  • 13 Khawaji M, Astermark J, Akesson K, Berntorp E. Physical activity and joint function in adults with severe haemophilia on long-term prophylaxis. Blood Coagul Fibrinolysis 2011; 22 (01) 50-55
  • 14 Boadas A, Osorio M, Gibraltar A. , et al; Desafio del Caribe Project. Favourable impact of regular swimming in young people with haemophilia: experience derived from ‘Desafio del Caribe’ project. Haemophilia 2015; 21 (01) e12-e18
  • 15 Kargarfard M, Dehghadani M, Ghias R. The effect of aquatic exercise therapy on muscle strength and joint's range of motion in hemophilia patients. Int J Prev Med 2013; 4 (01) 50-56
  • 16 Murtezani A, Nevzati A, Ibraimi Z, Sllamniku S, Meka VS, Abazi N. The effect of land versus aquatic exercise program on bone mineral density and physical function in postmenopausal women with osteoporosis: a randomized controlled trial. Ortop Traumatol Rehabil 2014; 16 (03) 319-325
  • 17 Vallejo L, Pardo A, Gomis M, Gallach JE, Pérez S, Querol F. Influence of aquatic training on the motor performance of patients with haemophilic arthropathy. Haemophilia 2010; 16 (01) 155-161
  • 18 Salim M, Brodin E, Spaals-Abrahamsson Y, Berntorp E, Zetterberg E. The effect of Nordic walking on joint status, quality of life, physical ability, exercise capacity and pain in adult persons with haemophilia. Blood Coagul Fibrinolysis 2016; 27 (04) 467-472
  • 19 Strike K, Mulder K, Michael R. Exercise for haemophilia. Cochrane Database Syst Rev 2016; 12: CD011180
  • 20 McGee S, Raffini L, Witmer C. Organized sports participation and the association with injury in paediatric patients with haemophilia. Haemophilia 2015; 21 (04) 538-542
  • 21 Runkel B, Czepa D, Hilberg T. RCT of a 6-month programmed sports therapy (PST) in patients with haemophilia - Improvement of physical fitness. Haemophilia 2016; 22 (05) 765-771
  • 22 Runkel B, Von Mackensen S, Hilberg T. RCT - subjective physical performance and quality of life after a 6-month programmed sports therapy (PST) in patients with haemophilia. Haemophilia 2017; 23 (01) 144-151
  • 23 Sondermann J, Herbsleb M, Stanek FD, Gabriel H, Kentouche K. Health promotion for young patients with haemophilia. Counselling, adjuvant exercise therapy and school sports. Hamostaseologie 2017; 37 (02) 107-116
  • 24 Negrier C, Seuser A, Forsyth A. , et al. The benefits of exercise for patients with haemophilia and recommendations for safe and effective physical activity. Haemophilia 2013; 19 (04) 487-498
  • 25 Philpott J, Houghton K, Luke A. Physical activity recommendations for children with specific chronic health conditions: juvenile idiopathic arthritis, hemophilia, asthma and cystic fibrosis. Paediatr Child Health 2010; 15 (04) 213-225
  • 26 Sherlock E, O'Donnell JS, White B, Blake C. Physical activity levels and participation in sport in Irish people with haemophilia. Haemophilia 2010; 16 (01) e202-e209
  • 27 Seuser A, Boehm P, Ochs S, Trunz-Carlisi E, Halimeh S, Klamroth R. How fit are children and adolescents with haemophilia in Germany? Results of a prospective study assessing the sport-specific motor performance by means of modern test procedures of sports science. Haemophilia 2015; 21 (04) 523-529
  • 28 Broderick CR, Herbert RD, Latimer J, van Doorn N. Patterns of physical activity in children with haemophilia. Haemophilia 2013; 19 (01) 59-64
  • 29 von Mackensen S, Harrington C, Tuddenham E. , et al. The impact of sport on health status, psychological well-being and physical performance of adults with haemophilia. Haemophilia 2016; 22 (04) 521-530
  • 30 Groen WG, Takken T, van der Net J, Helders PJ, Fischer K. Habitual physical activity in Dutch children and adolescents with haemophilia. Haemophilia 2011; 17 (05) e906-e912
  • 31 Buzzard BM. Physiotherapy, rehabilitation and sports in countries with limited replacement coagulation factor supply. Haemophilia 2007; 13 (Suppl. 02) 44-46
  • 32 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
  • 33 Lippi G, Maffulli N. Biological influence of physical exercise on hemostasis. Semin Thromb Hemost 2009; 35 (03) 269-276
  • 34 Prisco D, Francalanci I, Filippini M, Hagi MI. Physical exercise and hemostasis. Int J Clin Lab Res 1994; 24 (03) 125-131
  • 35 Smith JE. Effects of strenuous exercise on haemostasis. Br J Sports Med 2003; 37 (05) 433-435
  • 36 Wang JS. Exercise prescription and thrombogenesis. J Biomed Sci 2006; 13 (06) 753-761
  • 37 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
  • 38 Womack CJ, Ivey FM, Gardner AW, Macko RF. Fibrinolytic response to acute exercise in patients with peripheral arterial disease. Med Sci Sports Exerc 2001; 33 (02) 214-219
  • 39 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
  • 40 Groen WG, den Uijl IE, van der Net J, Grobbee DE, de Groot PG, Fischer K. Protected by nature? Effects of strenuous physical exercise on FVIII activity in moderate and mild haemophilia A patients: a pilot study. Haemophilia 2013; 19 (04) 519-523
  • 41 Koch B, Luban NL, Galioto Jr FM, Rick ME, Goldstein D, Kelleher Jr JF. Changes in coagulation parameters with exercise in patients with classic hemophilia. Am J Hematol 1984; 16 (03) 227-233
  • 42 Rizza CR. Effect of exercise on the level of antihaemophilic globulin in human blood. J Physiol 1961; 156: 128-135
  • 43 Beltrame LG, Abreu L, Almeida J, Boullosa DA. The acute effect of moderate intensity aquatic exercise on coagulation factors in haemophiliacs. Clin Physiol Funct Imaging 2015; 35 (03) 191-196
  • 44 Kumar R, Bouskill V, Schneiderman JE. , et al. Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia. Thromb Haemost 2016; 115 (06) 1120-1128
  • 45 Fijnvandraat K, Peters M, ten Cate JW. Inter-individual variation in half-life of infused recombinant factor VIII is related to pre-infusion von Willebrand factor antigen levels. Br J Haematol 1995; 91 (02) 474-476
  • 46 Al Dieri R, de Laat B, Hemker HC. Thrombin generation: what have we learned?. Blood Rev 2012; 26 (05) 197-203
  • 47 Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol 2014; 89 (02) 228-232
  • 48 Sucker C, Zotz RB, Senft B. , et al. Exercise-induced hemostatic alterations are detectable by rotation thrombelastography (ROTEM): a marathon study. Clin Appl Thromb Hemost 2010; 16 (05) 543-548
  • 49 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
  • 50 Hernández Madrid A, Potpara TS, Dagres N. , et al. Differences in attitude, education, and knowledge about oral anticoagulation therapy among patients with atrial fibrillation in Europe: result of a self-assessment patient survey conducted by the European Heart Rhythm Association. Europace 2016; 18 (03) 463-467
  • 51 Sholzberg M, Floros G, Schneiderman JE. , et al. Effect of moderate intensity exercise on haemostatic capacity in adults with haemophilia A and B: pilot study. Haemophilia 2017; 23 (02) e162-e165
  • 52 Krüger S, Weitz C, Runkel B, Hilberg T. Pain sensitivity in patients with haemophilia following moderate aerobic exercise intervention. Haemophilia 2016; 22 (06) 886-893
  • 53 Gilbert MS. Prophylaxis: musculoskeletal evaluation. Semin Hematol 1993; 30 (03) (Suppl. 02) 3-6
  • 54 Freynhagen R, Baron R, Gockel U, Tölle TR. painDETECT: a new screening questionnaire to identify neuropathic components in patients with back pain. Curr Med Res Opin 2006; 22 (10) 1911-1920
  • 55 Nagel B, Gerbershagen HU, Lindena G, Pfingsten M. [Development and evaluation of the multidimensional German pain questionnaire]. Schmerz 2002; 16 (04) 263-270
  • 56 Hilberg T, Czepa D, Freialdenhoven D, Boettger MK. Joint pain in people with hemophilia depends on joint status. Pain 2011; 152 (09) 2029-2035
  • 57 Borg G. Psychophysical scaling with applications in physical work and the perception of exertion. Scand J Work Environ Health 1990; 16 (Suppl. 01) 55-58
  • 58 Cooper KH. Aerobics. California: Bantam Books; 1969
  • 59 Gould D. Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated patient simulations to collect the data. J Clin Nurs 2001; 10 (05) 697-706
  • 60 Al-Sharif FA, Al-Jiffri OH, El-Kader SM, Ashmawy EM. Impact of mild versus moderate intensity aerobic walking exercise training on markers of bone metabolism and hand grip strength in moderate hemophilic A patients. Afr Health Sci 2014; 14 (01) 11-16
  • 61 Hilliard P, Funk S, Zourikian N. , et al. Hemophilia joint health score reliability study. Haemophilia 2006; 12 (05) 518-525
  • 62 Coopersmith S. Self-esteem Inventory. California: Consulting Psychologists Press; 1984
  • 63 Gimeno F, Buceta JM, Perez LM. El cuestionario caracteristicas paicologicas relacionadas con el rendimiento deportivo (CPRD): caracteristicas psicometricas. Análise psicológica 2001; 1: 93-113
  • 64 Martens R, Vealey RS, Burton D. Competitive anxiety in sport. Champaign, IL: Human Kinetics; 1990
  • 65 Jaenes JC, Caracuel JC, Pérez Gil JA. Adaptación española del test CSAI-2: un estudio en corredores españoles de maratón. Poster presented at the VII Congreso Nacional de la actividad física y del deporte, Murcia, España: Sociedad Murciana de Psicología de la Actividad Física y del Deporte, 1999
  • 66 Maldonado ML. Test persona bajo la lluvia. Available at: http://www.infogerontologia.com/documents/miscelanea/test_evaluacion/testpersonabajolalluvia.pdf2002 . Accessed March 1, 2018
  • 67 Simonton C, Matthews-Simonton S, Creigthon JL. Getting Well Again. Los Angeles: Tarcher; 1978
  • 68 McGavin CR, Gupta SP, McHardy GJ. Twelve-minute walking test for assessing disability in chronic bronchitis. BMJ 1976; 1 (6013): 822-823
  • 69 Bohannon RW, Larkin PA, Cook AC, Gear J, Singer J. Decrease in timed balance test scores with aging. Phys Ther 1984; 64 (07) 1067-1070
  • 70 von Mackensen S, Czepa D, Herbsleb M, Hilberg T. Development and validation of a new questionnaire for the assessment of subjective physical performance in adult patients with haemophilia--the HEP-Test-Q. Haemophilia 2010; 16 (01) 170-178
  • 71 Bullinger MKI. SF-36 Fragebogen zum Gesundheitszustand: Handanweisung. Gõttingen, Bern, Toronto, Seattle: Hogrefe-Verlag GmbH; 1998
  • 72 von Mackensen S, Gringeri A. Quality of life in hemophilia. In: Preedy VR, Watson RR. , eds. Handbook of Disease Burdens and Quality of Life. Heidelberg, Germany: Springer; 2010: 1896-1920
  • 73 Czepa D, von Mackensen S, Hilberg T. Haemophilia & Exercise Project (HEP): the impact of 1-year sports therapy programme on physical performance in adult haemophilia patients. Haemophilia 2013; 19 (02) 194-199
  • 74 Herbsleb M, Hilberg T. Maximal and submaximal endurance performance in adults with severe haemophilia. Haemophilia 2009; 15 (01) 114-121
  • 75 Hilberg T, Herbsleb M, Puta C, Gabriel HH, Schramm W. Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects. Haemophilia 2003; 9 (01) 86-93
  • 76 Hill K, Fearn M, Williams S. , et al. Effectiveness of a balance training home exercise programme for adults with haemophilia: a pilot study. Haemophilia 2010; 16 (01) 162-169
  • 77 Duncan PW, Weiner DK, Chandler J, Studenski S. Functional reach: a new clinical measure of balance. J Gerontol 1990; 45 (06) M192-M197
  • 78 Hill KBJ, McGann A, Maltese D, Berkovits D. A new test of dynamic standing balance for stroke patients: reliability, validity, and comparison with healthy elderly. Physiother Can 1996; 48: 257-262
  • 79 Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc 1991; 39 (02) 142-148
  • 80 Fix A, Daughton D. Human activity profile: professional manual. Odessa, FL: Psychological Assessment Resources Inc.; 1988
  • 81 Hill KD, Schwarz JA, Kalogeropoulos AJ, Gibson SJ. Fear of falling revisited. Arch Phys Med Rehabil 1996; 77 (10) 1025-1029
  • 82 Guyatt GH, Sullivan MJ, Thompson PJ. , et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J 1985; 132 (08) 919-923
  • 83 Von Mackensen S, Eifrig B, Zäch D, Kalnins J, Wieloch A, Zeller W. The impact of a specific aqua-training for adult haemophilic patients--results of the WATERCISE study (WAT-QoL). Haemophilia 2012; 18 (05) 714-721
  • 84 Khair K, Littley A, Will A, von Mackensen S. The impact of sport on children with haemophilia. Haemophilia 2012; 18 (06) 898-905
  • 85 Ravens-Sieberer U, Bullinger M. Assessing health-related quality of life in chronically ill children with the German KINDL: first psychometric and content analytical results. Qual Life Res 1998; 7 (05) 399-407
  • 86 von Mackensen S, Bullinger M. ; Haemo-QoL Group. Development and testing of an instrument to assess the Quality of Life of Children with Haemophilia in Europe (Haemo-QoL). Haemophilia 2004; 10 (Suppl. 01) 17-25
  • 87 Mount A, Xiong S, Shan X. , et al. Electrochemical conversion and storage systems: general discussion. Faraday Discuss 2014; 176: 153-184