Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 16, Issue 3, Pages 546-554Publisher
WILEY
DOI: 10.1111/jth.13934
Keywords
blood coagulation; platelet activation; von Willebrand disease; von Willebrand factor; von willebrand factor propolypeptide
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Funding
- National Institutes of Health [HL-081588]
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Background: Reduced plasma survival of von Willebrand factor (VWF) is characteristic of patients with type 1C von Willebrand disease (VWD). These subjects can be identified by an increased steady-state ratio of plasma VWF propeptide (VWFpp) to VWF antigen (VWF: Ag). A similar phenotype occurs in mice with the Mvwf1 allele. Objectives: To (i) determine if the VWFpp/VWF: Ag ratio can be used to identify a 'type 1C' phenotype in mice, (ii) determine the most reliable method for murine blood sampling, and (iii) identify the source of VWF released during problematic blood collection. Methods: 'Platelet-VWF' and 'endothelial-VWF' mice were generated by bone marrow transplantation between C57BL/6J and VWF-/- mice. Several blood sampling methods were used and murine VWFpp and VWF: Ag levels determined. Plasma and platelet VWF: Ag and VWFpp, VWF multimers and VWF halflife were examined in mouse strains with and without Mvwf1. Results: A single retro-orbital bleed and vena cava collection were found to be the optimal methods of blood collection. Problematic collection resulted in release of VWF from platelets and endothelium. The VWFpp/VWF: Ag ratio identified strains of mice with reduced VWF survival. Conclusion: Assay of murine VWFpp and VWF: Ag has utility in determining the acceptability of murine blood samples for coagulation testing and in identification of a reduced VWF survival phenotype in mice.
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