Paper Details

ABSTRACT

Introduction: Current treatment guidelines for von Willebrand disease (VWD) recommend long-term prophylaxis for selected patients with severe or recurrent bleeding manifestations. While regular prophylaxis remains the standard approach for most bleeding phenotypes, intermittent prophylaxis is increasingly used as a therapeutic option for females with VWD who experience heavy menstrual bleeding (HMB), although optimal timing and dosing strategy remain undefined. Real-world evidence regarding the implementation of phenotype-directed prophylactic strategies in pediatric patients remains limited. This retrospective case series describes a pediatric center’s experience with individualized prophylaxis using a plasma-derived von Willebrand Factor/Factor VIII (pdVWF/FVIII, 1:1 activity ratio) concentrate, tailored to the predominant bleeding phenotype.

Methods: We retrospectively reviewed de-identified records of pediatric patients with VWD receiving prophylactic pdVWF/FVIII concentrate at a Mexico City hematology center from 2020 to 2026. Prophylaxis was defined as ≥3 months of treatment, administered at least weekly for regular prophylaxis or once per menstrual cycle for HMB. Treatment regimens were individualized by the treating physician according to bleeding phenotype and clinical course. Data collected included demographic and clinical characteristics, VWD subtype, prophylaxis indication and regimen, treatment duration, bleeding outcomes, healthcare utilization and adverse events. Outcomes were summarized descriptively.

Results: Twelve patients (type 1, n=7 [58.3%]; type 2, n=4 [33.3%]; type 3, n=1 [8.3%]) initiated phenotype-directed prophylaxis at a median age of 12.5 years (range, 1-15). Indications included HMB in nine adolescents and severe epistaxis in three children.  No thromboembolic events, infusion-related reactions, or other treatment-related serious adverse events were observed during follow-up.

Among the nine adolescents with HMB (median [range] age 13 [11–15] years), seven initiated intermittent prophylaxis because of persistent HMB despite conventional therapy, including tranexamic acid alone (n=4) or combined with oral hormonal therapy (n=3), whereas two received prophylaxis as first-line therapy. All patients received 30 IU/kg pdVWF/FVIII per infusion. Regimens consisted of one infusion per menstrual cycle in six patients and two infusions per cycle in three, administered either on the first day of their menstruation (n=3), or on the day of heaviest menstrual bleeding (n=6). Patients received treatment over a mean of 10.8 menstrual cycles (median [range)] 8 [5–24]). Median (range) PBAC score decreased from 210 (105–300) before prophylaxis to 40 (0–55) during prophylaxis, representing a median (range) reduction of 78% (57.1–100%). Aggregate annualized HMB-related emergency department (ED) visits decreased from 24 to 6 (75% reduction), hospitalizations from 6 to 1 (83% reduction), and transfusions from 4 to 0 (100% reduction).

Among the three children with severe epistaxis (median [range] age 9 [1–10] years), individualized regular prophylaxis was initiated due to recurrent episodes requiring ED visits or hospitalizations. Initial regimens consisted of 20 IU/kg pdVWF/FVIII once weekly (n=1), 25 IU/kg twice weekly (n=1), and 30 IU/kg three times weekly (n=1). Aggregate annualized ED visits decreased from 15 to 5 (67% reduction) and hospitalizations from 10 to 3 (70% reduction). One patient initially treated with 20 IU/kg pdVWF/FVIII once weekly required escalation to 30 IU/kg, resulting in improved bleeding control.

Conclusions: In this single-center case series, phenotype-directed prophylaxis with a pdVWF/FVIII concentrate (1:1 activity ratio) was associated with clinically meaningful improvements in bleeding control, reduced healthcare utilization and a favorable safety profile in children and adolescents with VWD. These findings support the feasibility of tailoring prophylactic regimens according to the predominant bleeding phenotype, including intermittent prophylaxis for HMB. The need for regimen intensification in one patient further highlights that prophylactic strategies may require dynamic adjustment according to clinical response. Prospective multicenter studies are warranted to define optimal patient selection, timing of prophylaxis initiation, dosing strategies, and long-term outcomes, particularly for intermittent prophylaxis in HMB.