Pharmacokinetics-guided individualized management of physical activity in people with hemophilia_West China Medical Journal

Authors：

FENG Qiyang , SHI Weihong , ZHANG Houqiang , LIU Shufen ,  CHEN Lixia

Department of Rehabilitation Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China;

Corresponding author：

CHEN Lixia, Email: clx727@126.com

Keywords：

Hemophilia; physical activity; pharmacokinetics

DOI：

10.7507/1002-0179.202503163

Video：

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Exercise has been increasingly recognized in clinical guidelines as a recommended component of rehabilitation for people with hemophilia (PWH), with evidence supporting appropriate physical activity’s multifaceted benefits. During exercise, the bleeding risk in PWH exhibits a critical correlation with circulating clotting factor activities, where higher factor concentrations demonstrably reduce hemorrhagic events. However, economic constraints limit universal access to high-dose prophylactic clotting factor replacement therapy. Through pharmacokinetics (PK) monitoring of clotting factor, clinicians can strategically tailor exercise types and frequencies, or adjust factor replacement dosages based on activity-specific demands. This individualized approach not only enhances the cost-effectiveness of clotting factor utilization, but also improves safety by mitigating bleeding risks. This article examines the feasibility and recent advancements in PK-guided individualized physical activity prescriptions for PWH, presenting evidence-based insights to inform clinical practice and future research priorities.

Citation： FENG Qiyang, SHI Weihong, ZHANG Houqiang, LIU Shufen, CHEN Lixia. Pharmacokinetics-guided individualized management of physical activity in people with hemophilia. West China Medical Journal, 2025, 40(6): 968-972. doi: 10.7507/1002-0179.202503163 Copy

1.	Chowdary P, Carcao M, Kenet G, et al. Haemophilia. Lancet, 2025, 405(10480): 736-750.
2.	Atilla B, Güney-Deniz H. Musculoskeletal treatment in haemophilia. EFORT Open Rev, 2019, 4(6): 230-239.
3.	Collins PW, Björkman S, Fischer K, et al. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost, 2010, 8(2): 269-275.
4.	Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia, 2020, 26(Suppl 6): 1-158.
5.	中国血友病协作组, 中国罕见病联盟血友病学组. 中国血友病骨骼肌肉并发症康复评估与治疗专家共识. 罕见病研究, 2022, 1(4): 420-427.
6.	Mingot-Castellano ME, Parra R, Núñez R, et al. Improvement in clinical outcomes and replacement factor VIII use in patients with haemophilia A after factor VIII pharmacokinetic-guided prophylaxis based on Bayesian models with myPKFiT^®. Haemophilia, 2018, 24(5): e338-e343.
7.	Matlary RED, Grydeland M, Glosli H, et al. Factors associated with physical activity in young people with haemophilia A on prophylaxis. Haemophilia, 2023, 29(3): 900-909.
8.	Kennedy M, Roche S, McGowan M, et al. Physical activity, physical fitness and cardiometabolic risk amongst adults with moderate and severe haemophilia. Haemophilia, 2023, 29(1): 72-83.
9.	Cruz-Montecinos C, Pérez-Alenda S, Casaña J, et al. Effectiveness of progressive moderate-vigorous intensity elastic resistance training on quality of life and perceived functional abilities in people with hemophilia: Secondary analysis of a randomized controlled trial. Eur J Haematol, 2023, 110(3): 253-261.
10.	Ljungkvist M, Olofsson H, Funding E, et al. Coagulation factor VIII is vital for increasing global coagulation after physical exercise. Haemophilia, 2019, 25(2): e86-e93.
11.	Kumar R, Bouskill V, Schneiderman JE, et al. Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia. Thromb Haemost, 2016, 115(6): 1120-1128.
12.	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(2): e162-e165.
13.	Li KX, Xiao J, Zhao YQ, et al. Moderate-intensity exercise improves the thromboelastography coagulation index in children with severe hemophilia A. Blood Coagul Fibrinolysis, 2016, 27(7): 797-803.
14.	Merlen C, Zourikian N, Bonnefoy A, et al. Effect of ABO blood group on haemostatic parameters in severe haemophilia A patients performing acute moderate-intensity exercise. Blood Coagul Fibrinolysis, 2018, 29(7): 626-635.
15.	Kumar R, Dunn AL, Schneiderman JE, et al. Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial. Blood, 2022, 140(10): 1156-1166.
16.	Konkle BA, Quon DV, Raffini L, et al. A prospective observational study of antihemophilic factor (recombinant) prophylaxis related to physical activity levels in patients with hemophilia A in the United States (SPACE). J Blood Med, 2021, 12: 883-896.
17.	Croteau SE, Wheeler AP, Khan O, et al. Pharmacokinetic-tailored approach to hemophilia prophylaxis: medical decision making and outcomes. Res Pract Thromb Haemost, 2020, 4(2): 326-333.
18.	Martin AP, Burke T, Asghar S, et al. Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: an expert elicitation exercise. Haemophilia, 2020, 26(4): 711-717.
19.	Strike K, Mulder K, Michael R. Exercise for haemophilia. Cochrane Database Syst Rev, 2016, 12(12): CD011180.
20.	Matlary RED, Grinda N, Sayers F, et al. Promoting physical activity for people with haemophilia in the age of new treatments. Haemophilia, 2022, 28(6): 885-890.
21.	张文慧, 杨仁池. 应用 myPKFiT 解析药代动力学指导血友病 A 患者个体化用药的进展. 中国临床研究, 2022, 35(2): 264-266, 271.
22.	Park YS, Yoo KY, Park SK, et al. Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review. Blood Res, 2024, 59(1): 29.
23.	Mizoguchi Y, Hino M, Ueda H, et al. Effectiveness of PK-guided personalized recombinant FVIII treatment in patients with hemophilia A: clinical case experiences based on an observational study. J Blood Med, 2025, 16: 27-39.
24.	Chelle P, Hajducek D, Thibaudeau K, et al. Development of a plasminogen population pk model supporting prophylactic replacement therapy for plasminogen deficient patients within the WAPPS-hemo platform. Haemophilia, 2024, 30(4): 988-997.
25.	Iorio A, Keepanasseril A, Foster G, et al. Development of a web-accessible population pharmacokinetic service-hemophilia (WAPPS-hemo): study protocol. JMIR Res Protoc, 2016, 5(4): e239.
26.	王甜甜, 王杰, 乔翠翠, 等. myPKFiT^®软件在血友病 A 患者个体化治疗中的应用. 血栓与止血学, 2023, 29(6): 249-253.
27.	Moonla C, Sosothikul D, Pongtanakul B, et al. Practices and challenges for hemophilia management under resource constraints in Thailand. Orphanet J Rare Dis, 2023, 18(1): 110.
28.	Urasiński T, Paczóska K, Badowska W, et al. Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A. Front Pediatr, 2023, 11: 1084539.
29.	Ai D, Huang K, Li G, et al. Exploration of the minimum necessary FVIII level at different physical activity levels in pediatric patients with hemophilia A. Front Pediatr, 2022, 10: 1045070.
30.	Versloot O, Kemler E, Blokzijl J, et al. Clotting factor activity levels and bleeding risk in people with haemophilia playing sports. Haemophilia, 2023, 29(4): 1013-1023.
31.	Bukkems LH, Versloot O, Cnossen MH, et al. Association between sports participation, factor VIII levels and bleeding in hemophilia A. Thromb Haemost, 2023, 123(3): 317-325.
32.	Tomschi F, Hmida J, Herzig S, et al. Physical activity and factor VIII levels in patients with haemophilia: a real-world prospective observational study. Haemophilia, 2024, 30(2): 419-425.
33.	Croteau SE, Callaghan MU, Davis J, et al. Focusing in on use of pharmacokinetic profiles in routine hemophilia care. Res Pract Thromb Haemost, 2018, 2(3): 607-614.
34.	Srichumpuang C, Rakmanotham A, Moonla C, et al. Moderate- to vigorous-intensity physical activities for hemophilia A patients during low-dose pharmacokinetic-guided extended half-life factor VIII prophylaxis. Orphanet J Rare Dis, 2024, 19(1): 135.
35.	Stemberger M, Kallenbach F, Schmit E, et al. Impact of adopting population pharmacokinetics for tailoring prophylaxis in haemophilia A patients: a historically controlled observational study. Thromb Haemost, 2019, 119(3): 368-376.

1. Chowdary P, Carcao M, Kenet G, et al. Haemophilia. Lancet, 2025, 405(10480): 736-750.
2. Atilla B, Güney-Deniz H. Musculoskeletal treatment in haemophilia. EFORT Open Rev, 2019, 4(6): 230-239.
3. Collins PW, Björkman S, Fischer K, et al. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A: influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost, 2010, 8(2): 269-275.
4. Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia, 2020, 26(Suppl 6): 1-158.
5. 中国血友病协作组, 中国罕见病联盟血友病学组. 中国血友病骨骼肌肉并发症康复评估与治疗专家共识. 罕见病研究, 2022, 1(4): 420-427.
6. Mingot-Castellano ME, Parra R, Núñez R, et al. Improvement in clinical outcomes and replacement factor VIII use in patients with haemophilia A after factor VIII pharmacokinetic-guided prophylaxis based on Bayesian models with myPKFiT^®. Haemophilia, 2018, 24(5): e338-e343.
7. Matlary RED, Grydeland M, Glosli H, et al. Factors associated with physical activity in young people with haemophilia A on prophylaxis. Haemophilia, 2023, 29(3): 900-909.
8. Kennedy M, Roche S, McGowan M, et al. Physical activity, physical fitness and cardiometabolic risk amongst adults with moderate and severe haemophilia. Haemophilia, 2023, 29(1): 72-83.
9. Cruz-Montecinos C, Pérez-Alenda S, Casaña J, et al. Effectiveness of progressive moderate-vigorous intensity elastic resistance training on quality of life and perceived functional abilities in people with hemophilia: Secondary analysis of a randomized controlled trial. Eur J Haematol, 2023, 110(3): 253-261.
10. Ljungkvist M, Olofsson H, Funding E, et al. Coagulation factor VIII is vital for increasing global coagulation after physical exercise. Haemophilia, 2019, 25(2): e86-e93.
11. Kumar R, Bouskill V, Schneiderman JE, et al. Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia. Thromb Haemost, 2016, 115(6): 1120-1128.
12. 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(2): e162-e165.
13. Li KX, Xiao J, Zhao YQ, et al. Moderate-intensity exercise improves the thromboelastography coagulation index in children with severe hemophilia A. Blood Coagul Fibrinolysis, 2016, 27(7): 797-803.
14. Merlen C, Zourikian N, Bonnefoy A, et al. Effect of ABO blood group on haemostatic parameters in severe haemophilia A patients performing acute moderate-intensity exercise. Blood Coagul Fibrinolysis, 2018, 29(7): 626-635.
15. Kumar R, Dunn AL, Schneiderman JE, et al. Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial. Blood, 2022, 140(10): 1156-1166.
16. Konkle BA, Quon DV, Raffini L, et al. A prospective observational study of antihemophilic factor (recombinant) prophylaxis related to physical activity levels in patients with hemophilia A in the United States (SPACE). J Blood Med, 2021, 12: 883-896.
17. Croteau SE, Wheeler AP, Khan O, et al. Pharmacokinetic-tailored approach to hemophilia prophylaxis: medical decision making and outcomes. Res Pract Thromb Haemost, 2020, 4(2): 326-333.
18. Martin AP, Burke T, Asghar S, et al. Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: an expert elicitation exercise. Haemophilia, 2020, 26(4): 711-717.
19. Strike K, Mulder K, Michael R. Exercise for haemophilia. Cochrane Database Syst Rev, 2016, 12(12): CD011180.
20. Matlary RED, Grinda N, Sayers F, et al. Promoting physical activity for people with haemophilia in the age of new treatments. Haemophilia, 2022, 28(6): 885-890.
21. 张文慧, 杨仁池. 应用 myPKFiT 解析药代动力学指导血友病 A 患者个体化用药的进展. 中国临床研究, 2022, 35(2): 264-266, 271.
22. Park YS, Yoo KY, Park SK, et al. Evaluation of FVIII pharmacokinetic profiles in Korean hemophilia A patients assessed with myPKFiT: a retrospective chart review. Blood Res, 2024, 59(1): 29.
23. Mizoguchi Y, Hino M, Ueda H, et al. Effectiveness of PK-guided personalized recombinant FVIII treatment in patients with hemophilia A: clinical case experiences based on an observational study. J Blood Med, 2025, 16: 27-39.
24. Chelle P, Hajducek D, Thibaudeau K, et al. Development of a plasminogen population pk model supporting prophylactic replacement therapy for plasminogen deficient patients within the WAPPS-hemo platform. Haemophilia, 2024, 30(4): 988-997.
25. Iorio A, Keepanasseril A, Foster G, et al. Development of a web-accessible population pharmacokinetic service-hemophilia (WAPPS-hemo): study protocol. JMIR Res Protoc, 2016, 5(4): e239.
26. 王甜甜, 王杰, 乔翠翠, 等. myPKFiT^®软件在血友病 A 患者个体化治疗中的应用. 血栓与止血学, 2023, 29(6): 249-253.
27. Moonla C, Sosothikul D, Pongtanakul B, et al. Practices and challenges for hemophilia management under resource constraints in Thailand. Orphanet J Rare Dis, 2023, 18(1): 110.
28. Urasiński T, Paczóska K, Badowska W, et al. Real pandemic world results of pharmacokinetic-tailored personalized prophylaxis of bleeds in Polish children and adolescents with severe hemophilia A. Front Pediatr, 2023, 11: 1084539.
29. Ai D, Huang K, Li G, et al. Exploration of the minimum necessary FVIII level at different physical activity levels in pediatric patients with hemophilia A. Front Pediatr, 2022, 10: 1045070.
30. Versloot O, Kemler E, Blokzijl J, et al. Clotting factor activity levels and bleeding risk in people with haemophilia playing sports. Haemophilia, 2023, 29(4): 1013-1023.
31. Bukkems LH, Versloot O, Cnossen MH, et al. Association between sports participation, factor VIII levels and bleeding in hemophilia A. Thromb Haemost, 2023, 123(3): 317-325.
32. Tomschi F, Hmida J, Herzig S, et al. Physical activity and factor VIII levels in patients with haemophilia: a real-world prospective observational study. Haemophilia, 2024, 30(2): 419-425.
33. Croteau SE, Callaghan MU, Davis J, et al. Focusing in on use of pharmacokinetic profiles in routine hemophilia care. Res Pract Thromb Haemost, 2018, 2(3): 607-614.
34. Srichumpuang C, Rakmanotham A, Moonla C, et al. Moderate- to vigorous-intensity physical activities for hemophilia A patients during low-dose pharmacokinetic-guided extended half-life factor VIII prophylaxis. Orphanet J Rare Dis, 2024, 19(1): 135.
35. Stemberger M, Kallenbach F, Schmit E, et al. Impact of adopting population pharmacokinetics for tailoring prophylaxis in haemophilia A patients: a historically controlled observational study. Thromb Haemost, 2019, 119(3): 368-376.

West China Medical Journal

Pharmacokinetics-guided individualized management of physical activity in people with hemophilia

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