Factor XI promotes hemostasis in factor IX‐deficient mice
Author(s): ,
B. M. Mohammed
Affiliations:
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA. Department of Clinical Pharmacy, School of Pharmacy, Cairo University, Cairo, Egypt
,
Q. Cheng
Affiliations:
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA
,
A. Matafonov
Affiliations:
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA
,
D. M. Monroe
Affiliations:
Division of Hematology/Oncology, Department of Medicine, University of North Carolina‐Chapel Hill, Chapel Hill, USA
,
J. C. M. Meijers
Affiliations:
Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands. Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
D. Gailani
Affiliations:
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, USA
Correspondence: David Gailani, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 4918 TVC, 1301 Medical Center Drive, Nashville, TN 37232, USA|Tel.: +1 615 936 1505|E‐mail: dave.gailani@vanderbilt.edu
ISTH Academy. Gailani D. Oct 4, 2018; 234150
David Gailani
David Gailani

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Background
In humans, deficiency of coagulation factor XI may be associated with a bleeding disorder, but, until recently, FXI‐deficient mice did not appear to have a hemostatic abnormality. A recent study, however, indicated that FXI‐deficient mice show a moderate hemostatic defect in a saphenous vein bleeding (SVB) model.
Objectives
To study the effect of FXI on bleeding in mice with normal levels of the FXI substrate FIX and in mice lacking FIX (a murine model of hemophilia B).
Methods
Wild‐type mice and mice lacking either FIX (F9) or FXI (F11) were tested in the SVB model. The plasma levels of FXI in F11 mice were manipulated by infusion of FXI or its active form FXIa, or by overexpressing FXI by the use of hydrodynamic tail vein injection.
Results
F9 mice showed a significant defect in the SVB model, whereas F11 mice and wild‐type mice were indistinguishable. Intravenous infusion of FXI or FXIa into, or overexpression of FXI in, F9 mice improved hemostasis in the SVB model. Overexpression of a FXI variant lacking a FIX‐binding site also improved hemostasis in F9 mice.
Conclusions
Although we were unable to demonstrate a hemostatic defect in F11 mice in the SVB model, our results support the premise that supraphysiological levels of FXI improve hemostasis in F9 mice through FIX‐independent pathways.
Keyword(s)
bleeding, factor IX, factor XI, hemostasis, saphenous vein
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