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Impact of a Standardized, Moderate-Intensity Aerobic Exercise Regimen on Hemostasis in Adolescent Hemophilia A Carriers: A Pilot Investigation

1Dana Farber/Boston Children's Hospital, Cancer and Blood Disorders Center, Boston, United States, 2Harvard Medical School, Department of Pediatrics, Boston, United States, 3Hospital for Sick Children, University of Toronto, Pediatric Hematology/Oncology, Toronto, Canada, 4Research Institute, University of Toronto, Child Health Evaluative Sciences, Toronto, Canada, 5Nationwide Children's Hospital, Pediatric Hematology/Oncology, Columbus, United States, 6The Ohio State University School of Medicine, Department of Pediatrics, Columbus, United States, 7Abigail Wexner Research Institute, Center for Clinical and Translational Research, Columbus, United States, 8Research Institute, University of Toronto, Child Health Evaluative Services, Toronto, Canada, 9Queens University, Department of Pathology and Molecular Medicine, Kingston, Canada

Abstract Number: PB1242

Meeting: ISTH 2020 Congress

Theme: Pediatrics » Bleeding in Neonates and Children

Background: In a previous study (Kumar et al. Thromb Haemost; 2016), we documented a 2.3 fold increase in FVIII activity (FVIII:C) in adolescent males with mild hemophilia A (n=8) performing moderate-intensity aerobic-exercise
(MIA-exercise).

Aims: In this pilot-study, we investigated the impact of MIA-exercise on hemostasis in adolescent, hemophilia A carriers.

Methods: The study (clinicaltrials.gov: NCT03379974) was approved by the research ethics committee. 5 females who met eligibility criteria were invited to participate. Written consent/assent was obtained from parent/participant. After baseline (T0) blood work was drawn, participants were instructed to exercise on a cycle-ergometer using the previously-validated, progressively incremental Godfrey protocol, until they completed 3-minutes of cycling at 85 % of their predicted maximum heart-rate. Blood work was repeated at 30 (T1), 75 (T3) and 135 (T4) minutes from the start of exercise. Specimens were assessed for multiple coagulation labs including global hemostatic assays.

Results: Baseline demographic data are summarized in Table 1. All participants successfully completed the study protocol. Median (range) duration of exercise was 11 (10-15) minutes. MIA-exercise was associated with a 1.06
(1.0-1.9) fold change in FVIII:C (T1 compared to baseline), 0.94 (0.8-1.4) fold change in von Willebrand antigen (VWF:Ag), 1.03 (0.8-1.6) fold change in VWF activity, 1 (0.8-1.8) fold change in platelet count and 1.06 (1.01-1.14) fold change in endogenous-thrombin-potential. We additionally compared the FVIII:C and VWF:Ag changes associated with MIA-exercise to the participant’s historic desmopressin-challenge (Figure 1). FVIII:C and VWF:Ag changes associated with exercise were observed to be inferior to desmopressin.

Conclusions: This is the first study to investigate the impact of aerobic-exercise on hemostasis in carriers of hemophilia A. Despite exercising for a similar duration and intensity as males with mild hemophilia A, females did not show a significant increase in FVIII:C, VWF:Ag or platelet counts. Future directions include confirmation of this gender-based discrepancy and further investigation of its etiology.

Characteristics Participant 1 Participant 2 Participant 3 Participant 4 Participant 5
Age (years) 16 13 15 15 16
Body mass index (kg/m2) 18.7 26.7 20.7 23.5 19.2
Baseline FVIII:C (%) 57 24 54 60 52
F8 variant identified c.3808insA c.1910A>G c.1034T>C c.1034T>C c.6445G>T
Severity of hemophilia reported with F8 mutation Severe Mild/Severe Moderate Moderate Mild
Historic desmopressin response Responder Responder Responder Responder Responder
Baseline Physical Activity (measured using IPAQ) High High High High Moderate
Duration of exercise (min) 15 12 10 11 11

[Table 1: Baseline characteristics of study cohort]


[Figure 1: Comparison of FVIII:C and VWF:Ag change with exercise and desmopressin]

To cite this abstract in AMA style:

Kumar R, Carcao M, Gonzales A, Lischak J, Widener P, Stanek J, Waller A, Kerlin B, Kahr W, Rand M, Lillicrap D, Dunn A. Impact of a Standardized, Moderate-Intensity Aerobic Exercise Regimen on Hemostasis in Adolescent Hemophilia A Carriers: A Pilot Investigation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/impact-of-a-standardized-moderate-intensity-aerobic-exercise-regimen-on-hemostasis-in-adolescent-hemophilia-a-carriers-a-pilot-investigation/. Accessed November 28, 2023.

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