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Moderate Intensity Aerobic Exercise and Intranasal Desmopressin Additively Increase Factor VIII and von Willebrand Factor (VWF) Levels in Adolescent Males with Mild Hemophilia A – Principal Findings from a Randomized Trial

R. Kumar1,2, A. Dunn3,4, J. Scneiderman5,6, A. Gonzales3, V. Bouskill7, H. Ziegler3, P. Widener3, J. Stanek3, S. Bai8, F. Pluthero9, A. Waller3, C. Tarango10, S. Ahuja11, B. Kerlin3,4,12, W. Kahr7,9, M. Rand7,13, D. Lillicrap14, M. Carcao7,15

1Boston Children's Hospital, Pediatric Hematology/Oncology, Boston, United States, 2Harvard Medical School, Department of Pediatrics, Boston, United States, 3Nationwide Children's Hospital, Pediatric Hematology/Oncology, Columbus, United States, 4The Ohio State University School of Medicine, Department of Pediatrics, Columbus, United States, 5The Hospital for Sick Children, Physiology and Experimental Medicine, Toronto, Canada, 6University of Toronto, Kinesiology and Physical Education, Toronto, Canada, 7Hospital for Sick Children, University of Toronto, Pediatric Hematology/Oncology, Toronto, Canada, 8The Ohio State University Wexner Medical Center, Center for Biostatistics, Columbus, United States, 9Research Institute, The Hospital for Sick Children, Cell Biology Program, Toronto, Canada, 10Cincinnati Children's Hospital Medical Center, Hematology, Cincinnati, United States, 11Rainbow Babies and Children's Hospital, Pediatric Hematology/Oncology, Cleveland, United States, 12Abigail Wexner Research Institute, Center for Clinical and Translational Research, Columbus, United States, 13Research Institute, The Hospital for Sick Children, Center for Translational Medicine, Toronto, Canada, 14Queens University, Department of Pathology and Molecular Medicine, Kingston, Canada, 15Research Institute, The Hospital for Sick Children, Child Health Evaluative Sciences, Toronto, Canada

Abstract Number: PB1243

Meeting: ISTH 2020 Congress

Theme: Pediatrics » Bleeding in Neonates and Children

Background: Persons with mild-hemophilia A (MHA) may use intranasal desmopressin prior to sports. In a previous study we documented a 2.3-fold increase in FVIII activity (FVIII:C) in adolescents with MHA after moderate-intensity aerobic exercise (MIA-exercise).

Aims: We performed a randomized-trial of MIA-exercise versus intranasal desmopressin in adolescents with MHA. Our primary-objective was to compare the increase in FVIII:C with MIA-exercise versus desmopressin. We also examined changes in hemostatic parameters with the sequential administration of these interventions.

Methods: The study (clinicaltrials.gov: NCT03379974/NCT03136003) was conducted simultaneously at SickKids and Nationwide Children’s Hospital with research ethics approval. Written consent was obtained from 32-participants meeting eligibility criteria. Participants were randomized to one of four study arms (Figure 1). Blood work was obtained at baseline and three subsequent time-points. Participants randomized to exercise, cycled on an ergometer till they completed 3-minutes of cycling at 85% of their predicted maximum heart-rate. Standard weight-based dosing of desmopressin was used. Primary analysis was performed using a non-inferiority t-test. Secondary analyses were done using t-test and linear mixed-models.

Results: Mean age (±SD) at participation was 16.1 (±2.6) years, and mean baseline FVIII:C was 27.9 (±18.4)%. FVIII:C increased by 1.73 fold with MIA-exercise versus 2.24 fold with desmopressin (non-inferiority p=0.04) (Figure 2A). The change in VWF antigen, activity (Figure 2B) and endogenous thrombin potential were similar with both interventions. MIA-exercise, but not desmopressin was associated with a significant increase in platelet count. Sequential administration of MIA-exercise and desmopressin was associated with an additive increase in FVIII:C and VWF activity (Figure 2C,2D), though the impact of exercise alone was short-lived.

Conclusions: While MIA-exercise (compared to desmopressin) was associated with a similar increase in FVIII:C and VWF levels, its impact on hemostasis was brief. Combination of MIA-exercise and desmopressin resulted in an additive increase in multiple hemostatic parameters. These findings have significant implications for persons with MHA.


[Figure 1: Study design]


[Figure 2: Change in FVIII:C (2A) and VWF:GPIbM (2B) from baseline to T1. Change in FVIII:C (2C) and VWF:GPIbM (2D) across the 4 study arms]

To cite this abstract in AMA style:

Kumar R, Dunn A, Scneiderman J, Gonzales A, Bouskill V, Ziegler H, Widener P, Stanek J, Bai S, Pluthero F, Waller A, Tarango C, Ahuja S, Kerlin B, Kahr W, Rand M, Lillicrap D, Carcao M. Moderate Intensity Aerobic Exercise and Intranasal Desmopressin Additively Increase Factor VIII and von Willebrand Factor (VWF) Levels in Adolescent Males with Mild Hemophilia A – Principal Findings from a Randomized Trial [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/moderate-intensity-aerobic-exercise-and-intranasal-desmopressin-additively-increase-factor-viii-and-von-willebrand-factor-vwf-levels-in-adolescent-males-with-mild-hemophilia-a-principal-findings-f/. Accessed May 16, 2022.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/moderate-intensity-aerobic-exercise-and-intranasal-desmopressin-additively-increase-factor-viii-and-von-willebrand-factor-vwf-levels-in-adolescent-males-with-mild-hemophilia-a-principal-findings-f/

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