A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation
Issued Date
2023-05-09
Resource Type
ISSN
24739529
eISSN
24739537
Scopus ID
2-s2.0-85152391483
Pubmed ID
36583671
Journal Title
Blood Advances
Volume
7
Issue
9
Start Page
1915
End Page
1925
Rights Holder(s)
SCOPUS
Bibliographic Citation
Blood Advances Vol.7 No.9 (2023) , 1915-1925
Suggested Citation
Wan J., Tanratana P., Roest M., Gruber A., Pawlinski R., Wolberg A.S., Mackman N., Grover S.P. A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation. Blood Advances Vol.7 No.9 (2023) , 1915-1925. 1925. doi:10.1182/BLOODADVANCES.2022008720 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82968
Title
A novel mouse whole blood thrombin generation assay sensitive to FXI- and FIX-mediated amplification of coagulation
Author's Affiliation
Other Contributor(s)
Abstract
Thrombin generation (TG) assays serve as a valuable tool to study the amplifying roles of intrinsic pathway factors in human coagulation and provide functional insights into the increased bleeding observed in individuals deficient in factors (F) XI, IX, or VIII. Mice are used extensively in hemostasis research owing to the availability of coagulation factor-deficient mice. However, phenotypic differences between mouse and human TG have become apparent. In this study, we describe a novel, calibrated mouse whole blood (WB) TG assay used to assess the amplifying roles of intrinsic pathway factors in mouse coagulation. WB- and plasma-TG was triggered with either silica or tissue factor (TF) in samples from wild-type mice and mice deficient for FXII, FXI, or FIX. Expectedly, silica-triggered WB-TG and platelet-poor plasma (PPP)-TG were significantly reduced by deficiencies for FXII, FXI, or FIX. FXII deficiency had no effect on WB-TG or PPP-TG when triggered with TF. However, FXI deficiency resulted in significantly reduced WB-TG triggered by low concentrations of TF but had no effect on TF-triggered PPP-TG. FIX deficiency profoundly reduced WB-TG when triggered by low or high concentrations of TF whereas TG in PPP or platelet-rich plasma was only moderately reduced under these conditions. In conclusion, we have developed a novel mouse WB-TG assay with enhanced sensitivity to FXI- and FIX-dependent amplification of coagulation compared with an established plasma-TG assay. The enhanced sensitivity of WB-TG to FXI and FIX-dependent amplification of coagulation suggests an important role of blood cells in this process.