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DOI: 10.1160/TH15-09-0757
Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia
Results from a prospective cohort study Financial support: This study was supported by Pfizer, Canada.Publikationsverlauf
Received:
25. September 2015
Accepted after major revision:
11. Februar 2016
Publikationsdatum:
27. November 2017 (online)
Summary
This study investigated the impact of aerobic exercise on laboratory assessments of haemostatic activity in boys (5–18 years of age) with haemophilia A (HA) or B (HB), examining the hypothesis that laboratory coagulation parameters temporarily improve with exercise. Thirty subjects meeting eligibility criteria (19 HA; 11 HB; mean age: 12.8 years) were invited to participate. They underwent a replacement factor washout period and were advised against strenuous activity for three days prior to the planned intervention. At study visit, baseline blood samples were drawn prior to exercise on a stationary cycle ergometer, aiming to attain 3 minutes (min) of cycling at 85 % of predicted maximum heart rate. Blood work was repeated 5 min (t5) and 60 min (t60) post exercise completion. Samples were assessed for platelet count (PC), factor VIII activity (FVIII:C), von Willebrand antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and platelet function analysis (PFA-100); maximum rate of thrombus generation (MRTG) in blood was measured via thromboelastography and plasma peak thrombin generation (PTG) via calibrated automated thrombography. Mean duration of exercise was 13.9 (± 2.6) min. On average, t5 samples showed significant elevation, relative to baseline in PC, FVIII:C, VWF:Ag, VWF:RCo and PTG, while FVIII:C, VWF:Ag, VWF:RCo and MRTG were significantly elevated in t60 samples. Within the cohort, participants with severe HA showed no change in FVIII:C levels with exercise. The greatest improvement in haemostatic indices was observed in post-adolescent males with mild-moderate HA, who thus represent the group most likely to benefit from a reduction of bleeding risk in the setting of exercise.
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References
- 1 Stonebraker JS, Bolton-Maggs PH, Soucie MJ. et al. A study of variations in the reported haemophilia B prevalence around the world. Haemophilia 2012; 18: e91-94.
- 2 Stonebraker JS, Bolton-Maggs PH, Soucie JM. et al. A study of variations in the reported haemophilia A prevalence around the world. Haemophilia 2010; 16: 20-32.
- 3 Kumar R, Carcao M. Inherited abnormalities of coagulation: haemophilia, von Willebrand disease, and beyond. Paediatr Clin North Am 2013; 60: 1419-1441.
- 4 Manco-Johnson MJ, Abshire TC, Shapiro AD. et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe haemophilia. N Engl J Med 2007; 357: 535-544.
- 5 Nilsson IM, Berntorp E, Lofqvist T. et al. Twenty-five years’ experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 1992; 232: 25-32.
- 6 Souza JC, Simoes HG, Campbell CS. et al. Haemophilia and exercise. Int J Sports Med 2012; 33: 83-88.
- 7 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: 487-498.
- 8 Douma-van Riet DC, Engelbert RH, van Genderen FR. et al. Physical fitness in children with haemophilia and the effect of overweight. Haemophilia 2009; 15: 519-527.
- 9 Greene WB, Strickler EM. A modified isokinetic strengthening program for patients with severe haemophilia. Dev Med Child Neurol 1983; 25: 189-196.
- 10 Pelletier JR, Findley TW, Gemma SA. Isometric exercise for an individual with haemophilic arthropathy. Phys Ther 1987; 67: 1359-1364.
- 11 Beltrame LG, Abreu L, Almeida J. et al. The acute effect of moderate intensity aquatic exercise on coagulation factors in haemophiliacs. Clin Physiol Funct Imaging 2015; 35: 191-196.
- 12 Groen WG, den Uijl IE, van der Net J. et al. Protected by nature? Effects of strenuous physical exercise on FVIII activity in moderate and mild haemophilia A patients: a pilot study. Haemophilia 2013; 19: 519-523.
- 13 Ravanbod RTG, Baghaipour MR, Nad-Ali F. Effects of Ergometric Exercise on F-VIII Coagulant Activity in Mild and Moderate Haemophilia-A: A Chance to Reduce Injective Replacement Therapy. Pakistan J Biol Sci 2006; 09: 2823-2827.
- 14 Nazzaro AM, Owens S, Hoots WK. et al. Knowledge, attitudes, and behaviors of youths in the US haemophilia population: results of a national survey. Am J Public Health 2006; 96: 1618-1622.
- 15 Seuser A, Boehm P, Ochs S. et al. 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: 523-529.
- 16 Sherlock E, O’Donnell JS, White B. et al. Physical activity levels and participation in sport in Irish people with haemophilia. Haemophilia 2010; 16: e202-209.
- 17 Biere-Rafi S, Haak BW, Peters M. et al. The impairment in daily life of obese haemophiliacs. Haemophilia 2011; 17: 204-208.
- 18 Hofstede FG, Fijnvandraat K, Plug I. et al. Obesity: a new disaster for haemophilic patients? A nationwide survey. Haemophilia 2008; 14: 1035-1038.
- 19 Majumdar S, Morris A, Gordon C. et al. Alarmingly high prevalence of obesity in haemophilia in the state of Mississippi. Haemophilia 2010; 16: 455-459.
- 20 Majumdar S, Ostrenga A, Latzman RD. et al. Pharmacoeconomic impact of obesity in severe haemophilia children on clotting factor prophylaxis in a single institution. Haemophilia 2011; 17: 717-718.
- 21 van der Cammen-van Zijp MH, Ijsselstijn H, Takken T. et al. Exercise testing of pre-school children using the Bruce treadmill protocol: new reference values. Eur J Appl Physiol 2010; 108: 393-399.
- 22 van der Cammen-van Zijp MH, van den Berg-Emons RJ, Willemsen SP. et al. Exercise capacity in Dutch children: new reference values for the Bruce treadmill protocol. Scand J Med Sci Sports 2010; 20: e130-136.
- 23 Godfrey S, Davies CT, Wozniak E. et al. Cardio-respiratory response to exercise in normal children. Clin Sci 1971; 40: 419-431.
- 24 Hebestreit H. Exercise testing in children -- what works, what doesn’t, and where to go?. Paediatr Respir Rev 2004; 05 (Suppl A) S11-14.
- 25 Rowland TW. Aerobic Exercise Testing Protocols. Rowland TW. Champaign, IL: Human Kinetics Publishers; 1993
- 26 Luddington R, Baglin T. Clinical measurement of thrombin generation by calibrated automated thrombography requires contact factor inhibition. J Thromb Haemost 2004; 02: 1954-1959.
- 27 Hemker HC, Al Dieri R, Beguin S. Thrombin generation assays: accruing clinical relevance. Curr Opin Haematol 2004; 11: 170-175.
- 28 Revel-Vilk S, Blanchette VS, Sparling C. et al. DDAVP challenge tests in boys with mild/moderate haemophilia A. Br J Haematol 2002; 117: 947-951.
- 29 Seary ME, Feldman D, Carcao MD. DDAVP responsiveness in children with mild or moderate haemophilia A correlates with age, endogenous FVIII:C level and with haemophilic genotype. Haemophilia 2012; 18: 50-55.
- 30 Kaufmann JE, Oksche A, Wollheim CB. et al. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J Clin Invest 2000; 106: 107-116.
- 31 Turner NA, Moake JL. Factor VIII Is Synthesized in Human Endothelial Cells, Packaged in Weibel-Palade Bodies and Secreted Bound to ULVWF Strings. PloS one 2015; 10: e0140740.
- 32 Lippi G, Maffulli N. Biological influence of physical exercise on haemostasis. Semin Thromb Haemost 2009; 35: 269-276.
- 33 Dimitriadou C, Dessypris A, Louizou C. et al. Marathon run II: Effects on platelet aggregation. Thromb Haemost 1977; 37: 451-455.
- 34 Hilberg T, Schmidt V, Glaser D. et al. Platelet activity, sensitivity to agonist, and platelet--leukocyte conjugate formation after long-term exercise. Platelets 2002; 13: 273-277.
- 35 Kestin AS, Ellis PA, Barnard MR. et al. Effect of strenuous exercise on platelet activation state and reactivity. Circulation 1993; 88: 1502-1511.
- 36 Kratz A, Wood MJ, Siegel AJ. et al. Effects of marathon running on platelet activation markers : direct evidence for in vivo platelet activation. Am J Clin Pathol 2006; 125: 296-300.
- 37 Rock G, Tittley P, Pipe A. Coagulation factor changes following endurance exercise. Clin J Sport Med 1997; 07: 94-99.
- 38 Lin X, El-Sayed MS, Waterhouse J. et al. Activation and disturbance of blood haemostasis following strenuous physical exercise. Int J Sports Med 1999; 20: 149-153.
- 39 van den Burg PJ, Hospers JE, van Vliet M. et al. Unbalanced haemostatic changes following strenuous physical exercise. A study in young sedentary males. Eur Heart J 1995; 16: 1995-2001.
- 40 Ribeiro J, Almeida-Dias A, Ascensao A. et al. Haemostatic response to acute physical exercise in healthy adolescents. J Sci Med Sport 2007; 10: 164-169.
- 41 Andrew M, Carter C, O’Brodovich H. et al. Increases in factor VIII complex and fibrinolytic activity are dependent on exercise intensity. J Appl Physiol 1986; 60: 1917-1922.
- 42 Ferguson EW, Bernier LL, Banta GR. et al. Effects of exercise and conditioning on clotting and fibrinolytic activity in men. J Appl Physiol 1987; 62: 1416-1421.
- 43 Koch B, Luban NL, Galioto Jr FM. et al. Changes in coagulation parameters with exercise in patients with classic haemophilia. Am J Haematol 1984; 16: 227-233.
- 44 van den Burg PJ, Hospers JE, Mosterd WL. et al. Aging, physical conditioning, and exercise-induced changes in haemostatic factors and reaction products. J Appl Physiol 2000; 88: 1558-1564.
- 45 Small M, Tweddel AC, Rankin AC. et al. Blood coagulation and platelet function following maximal exercise: effects of beta-adrenoceptor blockade. Haemostasis 1984; 14: 262-268.
- 46 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; 06: 90-96.
- 47 Posthuma JJ, van der Meijden PE, Ten Cate H. et al. Short- and Long-term exercise induced alterations in haemostasis: a review of the literature. Blood Rev 2015; 29: 171-178.
- 48 Schmidt KG, Rasmussen JW. Exercise-induced changes in the in vivo distribution of 111In-labelled platelets. Scand J Haematol 1984; 32: 159-166.