Papers of the Week

Persons with mild hemophilia A (HA) may use intranasal desmopressin prior to sports participation. Desmopressin is expensive, and can cause vomiting, headache, palpitation and occasionally seizures. Our group has previously documented a 2.3-fold increase in FVIII activity (FVIII:C) in adolescents with mild HA after moderate-intensity aerobic exercise. Herein, we report principal findings of a randomized trial of intranasal desmopressin versus a standardized, moderate-intensity aerobic exercise regimen in adolescents with mild HA. Our primary objective was to compare the change in FVIII:C associated with these two interventions. We also examined changes in hemostatic parameters arising from their sequential administration. The study was conducted simultaneously at the Hospital for Sick Children, Canada and Nationwide Children's Hospital, USA. Thirty-two eligible male adolescents [mean age (±SD): 16.1 (±2.6) years] with mild HA [mean baseline FVIII:C: 27.9 (±18.4)%] were randomized to one of four study arms (desmopressin followed by exercise, desmopressin alone, exercise followed by desmopressin, and exercise alone). Blood work was obtained at baseline, and at three subsequent time-points. Participants randomized to exercise cycled on an ergometer for approximately 12-minutes, with the final 3-minutes at 85% of their predicted maximum heart-rate. Standard weight-based dosing of desmopressin was used. Mean immediate increase in FVIII:C was 1.7-fold with exercise, compared to 1.9-fold with desmopressin (non-inferiority p=0.04). Exercise-induced improvement in hemostatic parameters including FVIII:C was brief, compared to more sustained improvements seen with desmopressin. More than 60% of participants randomized to receive both exercise and desmopressin achieved normal (>50%) FVIII:C, 75- and 135-minutes into the study protocol. Clinicaltrials.gov NCT03379974; NCT03136003.