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von Willebrand factor propeptide to antigen ratio identifies platelet activation and reduced von Willebrand factor survival phenotype in mice
Author(s) -
Jacobi P. M.,
Kanaji S.,
Jakab D.,
Gehrand A. L.,
Johnsen J. M.,
Haberichter S. L.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13934
Subject(s) - von willebrand factor , von willebrand disease , platelet , coagulation , medicine , antigen , protein precursor , endocrinology , immunology , blood sampling , chemistry , microbiology and biotechnology , biology , biochemistry , gene
Essentials Reduced survival of von Willebrand factor (VWF) in plasma causes type 1C von Willebrand disease. Blood was collected from mouse strains by various methods and VWF propeptide and antigen assayed. VWF propeptide to antigen ratio identifies a reduced VWF survival phenotype in mice. This ratio validates the acceptability of murine blood samples for coagulation studies.Summary 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 ( VWF pp) to VWF antigen ( VWF :Ag). A similar phenotype occurs in mice with the Mvwf1 allele. Objectives To (i) determine if the VWF pp/ 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 C57 BL /6J and VWF ‐/‐ mice. Several blood sampling methods were used and murine VWF pp and VWF :Ag levels determined. Plasma and platelet VWF :Ag and VWF pp, VWF multimers and VWF half‐life 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 VWF pp/ VWF :Ag ratio identified strains of mice with reduced VWF survival. Conclusion Assay of murine VWF pp 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.