@article{153a2f619d094c4ab8e3b6724c87760b,
title = "Thromboelastometry assessment of hemostatic properties in various murine models with coagulopathy and the effect of factor VIII therapeutics",
abstract = "Background: Rotational thromboelastometry (ROTEM) has been commonly used to assess the viscoelastic properties of the blood clotting process in the clinic for patients with a hemostatic or prothrombotic disorder. Objective: To evaluate the capability of ROTEM in assessing hemostatic properties in whole blood from various mouse models with genetic bleeding or clotting disease and the effect of factor VIII (FVIII) therapeutics in FVIIInull mice. Methods: Mice with a genetic deficiency in either a coagulation factor or a platelet glycoprotein were used in this study. The properties of platelet- or plasma-FVIII were also assessed. Citrated blood from mice was recalcified and used for ROTEM analysis. Results: We found that blood collected from the vena cava could generate reliable results from ROTEM analysis, but not blood collected from the tail vein, retro-orbital plexus, or submandibular vein. Age and sex did not significantly affect the hemostatic properties determined by ROTEM analysis. Clotting time (CT) and clot formation time (CFT) were significantly prolonged in FVIIInull (5- and 9-fold, respectively) and FIXnull (4- and 5.7-fold, respectively) mice compared to wild-type (WT)-C57BL/6J mice. Platelet glycoprotein (GP)IIIanull mice had significantly prolonged CFT (8.4-fold) compared to WT-C57BL/6J mice. CT and CFT in factor V (FV) Leiden mice were significantly shortened with an increased α-angle compared to WT-C57BL/6J mice. Using ROTEM analysis, we showed that FVIII expressed in platelets or infused into whole blood restored hemostasis of FVIIInull mice in a dose-dependent manner. Conclusion: ROTEM is a reliable and sensitive assay for assessing therapeutics on hemostatic properties in mouse models with a bleeding or clotting disorder.",
keywords = "bleeding, clotting, mouse model, rotational thromboelastometry",
author = "Schroeder, {Jocelyn A.} and Kuether, {Erin A.} and Juan Fang and Weiqing Jing and Hartmut Weiler and Wilcox, {David A.} and Montgomery, {Robert R.} and Qizhen Shi",
note = "Funding Information: We thank H. Kazazian at the University of Pennsylvania School of Medicine (Philadelphia, Pennsylvania, USA) for the FVIII knockout mice. We thank J. Ware at the University of Arkansas for Medical Sciences (Little Rock, Arkansas, USA) for GPIbα knockout mice. We thank R. O. Hynes at the Howard Hughes Medical Institute (Cambridge, Massachusetts, USA) for β3-/- mice. This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health grants HL-102035 (QS), HL-139847 (RRM), and HL-081588 (RRM), and generous gifts from the Children{\textquoteright}s Wisconsin Foundation (QS), Midwest Athletes Against Childhood Cancer and Bleeding Disorder (MACC) Fund (QS), Versiti Blood Research Foundation (RRM), and John & Judith Gardetto and the Glanzmann Research Foundation (DAW). Funding Information: We thank H. Kazazian at the University of Pennsylvania School of Medicine (Philadelphia, Pennsylvania, USA) for the FVIII knockout mice. We thank J. Ware at the University of Arkansas for Medical Sciences (Little Rock, Arkansas, USA) for GPIbα knockout mice. We thank R. O. Hynes at the Howard Hughes Medical Institute (Cambridge, Massachusetts, USA) for β3 mice. This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health grants HL‐102035 (QS), HL‐139847 (RRM), and HL‐081588 (RRM), and generous gifts from the Children{\textquoteright}s Wisconsin Foundation (QS), Midwest Athletes Against Childhood Cancer and Bleeding Disorder (MACC) Fund (QS), Versiti Blood Research Foundation (RRM), and John & Judith Gardetto and the Glanzmann Research Foundation (DAW). ‐/‐ Publisher Copyright: {\textcopyright} 2021 International Society on Thrombosis and Haemostasis",
year = "2021",
month = oct,
doi = "10.1111/jth.15456",
language = "English (US)",
volume = "19",
pages = "2417--2427",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "10",
}