Firstly, since thrombin has also been shown to cleave platelet-bound VWF under flow so that excessive and sustained generation of thrombin would restrict the presence of VWF to its release point28, a greater overall ETP may explain why (in contrast to clinical experience with TTP in humans) no animal has ever demised or suffered from excessive bleeding, in any of the preclinical studies conducted in this model. This evidence concerns the gene VWF and thrombotic thrombocytopenic purpura.