Mouse models to study von Willebrand factor in thrombosis: a scoping review.

Background: von Willebrand factor (VWF) plays a significant role in blood coagulation and inflammation and is a key driver of many thrombotic conditions. Identifying appropriate mouse models is critical to developing effective and safe VWF-targeted therapies. Objectives: This scoping review aims to identify and evaluate all mouse models of thrombosis that have demonstrated functional involvement of VWF and/or its primary regulator, ADAMTS-13, followed by a critical review of common models. Methods: A comprehensive literature search was conducted to identify studies published from database inception to October 2024 that used mouse models of thrombosis. Two reviewers independently screened and extracted data on model methodology and outcomes, as well as secondary measures of thrombosis if they pertain directly to VWF or indirectly through ADAMTS-13. Results: A total of 143 studies published between 2000 and 2024 were included; 32.6% models used C57BL/6 mice, and 32.7% used male mice only. Mice age and weight were reported in 79.7% and 30.8% of studies, respectively. Ferric chloride models were used in 45 (31.5%) studies, and laser injury models in 14 (9.8%). The most common systemic thrombosis model was thrombotic thrombocytopenic purpura (21 studies, 14.7%), and there were 16 other diseases studied with secondary thrombosis outcomes pertaining to VWF. Conclusion: There is significant methodological heterogeneity across mouse models of thrombosis that have demonstrated involvement of VWF. Lack of standardization negatively impacts cross-study comparability and hinders the strength of preclinical studies of novel therapeutics. Standardization of model methodology is urgently needed, and in the future, researchers should consider the impact of methodology on VWF-related outcomes when designing their studies.