There is significant methodological heterogeneity across mouse models of thrombosis that have demonstrated involvement of VWF, and standardization of model methodology is urgently needed to improve cross-study comparability and strengthen preclinical studies of novel therapeutics.
Key Findings
Methods
A total of 143 studies published between 2000 and 2024 were included in this scoping review of mouse models of thrombosis involving VWF and/or ADAMTS-13.
Studies were identified through a comprehensive literature search from database inception to October 2024.
Two reviewers independently screened and extracted data on model methodology and outcomes.
Secondary measures of thrombosis were included if they pertained directly to VWF or indirectly through ADAMTS-13.
The publication range spanned from 2000 to 2024.
Results
C57BL/6 mice were the most commonly used mouse strain, used in 32.6% of included studies.
32.6% of models used C57BL/6 mice.
32.7% of studies used male mice only.
Mouse age was reported in 79.7% of studies.
Mouse weight was reported in only 30.8% of studies, indicating incomplete reporting of animal characteristics.
Results
Ferric chloride models were the most commonly used thrombosis model, appearing in 45 (31.5%) of studies.
Ferric chloride models were used in 45 studies, representing 31.5% of all included studies.
Laser injury models were the second most commonly used, appearing in 14 studies (9.8%).
Significant methodological heterogeneity was identified across these injury-based thrombosis models.
Results
Thrombotic thrombocytopenic purpura (TTP) was the most common systemic thrombosis model, appearing in 21 studies (14.7%).
TTP was studied in 21 studies, representing 14.7% of included studies.
There were 16 other diseases studied with secondary thrombosis outcomes pertaining to VWF.
This highlights the range of thrombotic conditions in which VWF functional involvement has been demonstrated in mouse models.
Results
Significant methodological heterogeneity exists across mouse models of thrombosis that have demonstrated involvement of VWF, negatively impacting cross-study comparability.
Lack of standardization was identified as a key limitation negatively impacting cross-study comparability.
Methodological heterogeneity was found in model methodology and outcome reporting.
The heterogeneity was deemed to hinder the strength of preclinical studies of novel therapeutics.
Standardization of model methodology was described as 'urgently needed.'
Results
Incomplete reporting of animal characteristics, particularly mouse weight, was identified as a widespread issue across included studies.
Mouse age was reported in 79.7% of studies, leaving approximately 20% of studies without this information.
Mouse weight was reported in only 30.8% of studies.
This incomplete reporting contributes to methodological heterogeneity and limits reproducibility.
Conclusions
The review concludes that researchers should consider the impact of methodology on VWF-related outcomes when designing future studies.
The authors call for consideration of how methodology choices affect VWF-related outcomes in study design.
Standardization is recommended to improve the translational value of preclinical thrombosis research.
The review covers both direct VWF models and models involving ADAMTS-13, VWF's primary regulator.
What This Means
This research systematically reviewed 143 scientific studies published between 2000 and 2024 that used mice to study a blood-clotting protein called von Willebrand factor (VWF) and its role in dangerous blood clot conditions (thrombosis). VWF is important in both blood clotting and inflammation, and it is regulated by another protein called ADAMTS-13. The researchers catalogued which types of mice were used, how experiments were designed, and what outcomes were measured, in order to assess the overall quality and consistency of this body of research.
The review found that there is a wide variety of methods being used across studies, with the most common mouse strain being C57BL/6 (used in about one-third of studies) and the most common clotting model being the ferric chloride injury model (used in nearly one-third of studies). Importantly, many studies failed to report basic details about their animals — for example, only about 31% of studies reported mouse weight, even though this can affect experimental results. The most commonly studied disease was thrombotic thrombocytopenic purpura (TTP), a rare but severe blood-clotting disorder, which appeared in about 15% of studies.
This research suggests that the lack of consistent methods across studies makes it difficult to compare results or build confidently on previous findings, which could slow the development of new VWF-targeted treatments. The authors argue that the field urgently needs standardized approaches so that scientists can more reliably translate findings from mouse experiments into effective therapies for humans with clotting disorders. They recommend that future researchers carefully consider how their experimental design choices may affect VWF-related outcomes.
DeYoung V, Masood H, Andrisani P, Kodeeswaran A, Sparring T, Arora J, et al.. (2026). Mouse models to study von Willebrand factor in thrombosis: a scoping review.. Research and practice in thrombosis and haemostasis. https://doi.org/10.1016/j.rpth.2026.106863