Mouse models to study von Willebrand Factor in hemostasis: a scoping review.

BACKGROUND: VWF and its primary molecular regulator, ADAMTS13, play an important role in hemostasis. Their dysfunction has been increasingly linked to numerous bleeding, thrombotic, and inflammatory conditions. Murine bleeding models are widely used to study their role and assess therapeutic efficacy of targeted agents. Despite this, no review has systematically identified and compared bleeding models proven to involve VWF or ADAMTS13 in vivo. This scoping review addresses this gap by identifying models, associated outcomes, and evaluating methodological inconsistencies that may impact translatability. METHODS: A comprehensive literature search was conducted to identify studies using murine models of hemostasis from inception to October 2024. Two reviewers independently screened articles and extracted data on mouse characteristics, bleeding induction methods, and VWF or ADAMTS13-related findings. RESULTS: 35 studies published between 1997 and 2024 were included; 40.0% utilized C57BL/6J mice and 40.0% of models used both sexes. Fourteen (40.0%) studies did not report the mouse supplier, and 20.0% and 80.0% did not report the age and weight of mice, respectively. Most studies (91.4%) used the tail tip transection model, 5.7% employed saphenous vein bleed, and 5.7% performed tail vein transection. Key methodological variations pertained to bleeding quantification, maximum observation time, and length of tail tip removed. CONCLUSIONS: This review highlights that most studies assessing VWF-related hemostasis use a single model, but there is methodological variability, limiting reproducibility and translational relevance. Standardized protocols and collaborative efforts to establish consensus guidelines are urgently needed to improve cross-study comparisons to strengthen preclinical therapeutic testing.