Cedric Hermans, Robert F. Sidonio
We read with great interest the publication by Horvais et al.[ 1 ] (Semin Thromb Hemost 2026; doi: 10.1055/a-2779-9176), which provides valuable real-world data from the Hopscotch Will II study comparing recombinant von Willebrand factor (rVWF) with plasma-derived VWF (pdVWF) concentrates during hospitalization. The authors should be congratulated for providing important real-world data on inpatient management of von Willebrand disease (VWD). Such real-world data on product utilization and dosing patterns in VWD remain limited, making observational multicenter analyses particularly valuable for informing everyday clinical practice. However, we would like to comment on a key methodological aspect of the primary analysis that is central to interpretation of the results: the aggregation of all plasma-derived VWF products into a single “pdVWF” comparator group. Plasma-derived VWF concentrates do not represent a homogeneous therapeutic category. They differ substantially in their Factor VIII (FVIII):VWF ratio, multimer composition, pharmacokinetic (PK) behavior, and consequently in dosing considerations and monitoring strategies.[ 2 ] [ 3 ] For a study focused on product utilization and consumption, such aggregation of FVIII/VWF concentrates (including highly purified pdVWF concentrates and with ratios such as 1:1 or 1:2.4) into single analytical category may obscure clinically meaningful differences between individual pdVWF products. This concern is reinforced by the product-specific data presented in Supplementary Material 4. Among treated adults, mean annual VWF consumption per patient was 29.58 IU/kg for the 1:1 FVIII/VWF concentrate, 34.04 IU/kg for highly purified pdVWF concentrate, 61.87 IU/kg for the 1:2.4 FVIII/VWF concentrate, and 39.15 IU/kg for rVWF. These data clearly demonstrate substantial heterogeneity within the pooled pdVWF category. Notably, the lowest mean annual VWF consumption in this cohort was observed with the 1:1 pdFVIII/VWF concentrate, rather than with rVWF. In that context, class-level interpretation should be approached with caution. The suggestion that “pdVWF” as a class may require higher dosing than rVWF may be misleading without consideration of intraclass variability. Differences in consumption appear largely driven by product-specific characteristics rather than by an intrinsic superiority of one therapeutic class over another (i.e., rVWF vs “pdVWF” concentrates). From a clinical standpoint, this distinction is critical. VWF concentrates are not interchangeable, and dosing should be individualized according to product composition, PK, treatment setting, and clinical context (including bleeding severity, type of procedure, baseline FVIII levels, and patient-specific risk factors). Broad comparisons between a single rVWF product and a heterogenous pdVWF comparator group without acknowledging intraclass variability may inadvertently promote underdosing when switching between products, with potentially serious consequences for patient safety. We believe that product-to-product comparisons, rather than comparisons of one single product against a heterogeneous group, provide a more accurate and clinically relevant framework for interpreting real-world unitization data in VWD. In summary, the work presented by Horvais et al.[ 1 ] represents an important contribution to the field. At the same time, careful interpretation of the product-specific data indicates that pdVWF concentrates differ substantially in dosing requirements, and that 1:1 FVIII/VWF product demonstrated VWF consumption comparable to, or lower than, rVWF in this cohort. Recognition of these differences is essential to support optimal, individualized patient care. Publication History Received: 29 April 2026 Accepted: 05 May 2026 Article published online: 22 May 2026 © 2026. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA