Absence of hematopoietic tissue factor pathway inhibitor mitigates bleeding in mice with hemophilia.

Proceedings of the National Academy of Sciences of the United States of America
S A MaroneyA E Mast

Abstract

Tissue factor pathway inhibitor (TFPI) blocks thrombin generation via the extrinsic blood coagulation pathway. Because the severe bleeding in patients with hemophilia occurs from deficiency of intrinsic blood coagulation pathway factor VIII or IX, pharmacological agents that inactivate TFPI and, therefore, restore thrombin generation via the extrinsic pathway, are being developed for treatment of hemophilia. Murine models of combined TFPI and factor VIII deficiency were used to examine the impact of TFPI deficiency on bleeding and clotting in hemophilia. In breeding studies, Factor VIII null (F8(-/-)) did not rescue the embryonic death of TFPI null (Tfpi(-/-)) mice. Tfpi(+/-) did not alter the bleeding phenotype of F8(-/-) mice. However, total inhibition of intravascular TFPI through injection of anti-TFPI antibody mitigated tail vein bleeding. Interestingly, tail blood loss progressively decreased at doses greater than needed to totally inhibit plasma TFPI, suggesting that inhibition of a sequestered pool of TFPI released at the injury site mitigates bleeding. Because TFPI is sequestered within platelets and released following their activation, the function of platelet TFPI was examined in F8(-/-) mice lacking hematopoietic ce...Continue Reading

References

Oct 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D RepkeY Nemerson
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M S BajajS P Bajaj
Jul 1, 1995·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·E ErhardtsenO Nordfang
Mar 21, 1998·The Journal of Biological Chemistry·R J BaughS Krishnaswamy
Sep 18, 1964·Science·E W DAVIE, O D RATNOFF
May 9, 2009·Journal of Thrombosis and Haemostasis : JTH·S A MaroneyA E Mast
Feb 24, 2010·Thrombosis Research·Susan A MaroneyAlan E Mast
Aug 3, 2010·Nature Medicine·Steffen MassbergBernd Engelmann
Jan 15, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Susan A MaroneyAlan E Mast
Mar 12, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Brian C Cooley
Jan 1, 2010·Thrombosis·Isis S R CarterRoss T A Macgillivray

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Citations

Oct 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jeremy P WoodAlan E Mast
Oct 13, 2015·British Journal of Haematology·Mike Laffan
Apr 16, 2014·The Journal of Pediatrics·Alan D Rogol, Gregory F Hayden
May 2, 2013·Blood Reviews·Kristien WinckersTilman M Hackeng
Mar 5, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·P B JohansenT Knudsen
Mar 6, 2015·Journal of Atherosclerosis and Thrombosis·Hideo WadaNaoyuki Katayama
Apr 3, 2015·Thrombosis and Haemostasis·Florry E van den BoogaardTom van der Poll
Mar 14, 2013·Journal of Thrombosis and Haemostasis : JTH·S A MaroneyA E Mast
Jan 26, 2013·Journal of Thrombosis and Haemostasis : JTH·S PeraramelliM Dockal
Jun 15, 2013·Journal of Thrombosis and Haemostasis : JTH·M Escobar, S Sallah
Dec 19, 2014·Haemophilia : the Official Journal of the World Federation of Hemophilia·S Shetty, K Ghosh
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·S A Maroney, A E Mast
Mar 13, 2014·Blood·Jeremy P WoodAlan E Mast
May 22, 2016·Thrombosis Research·Cristina PuyOwen J T McCarty
May 22, 2016·Thrombosis Research·Julie A PetersonAlan E Mast
Jan 11, 2018·Blood·Raja PrinceAnne Angelillo-Scherrer
Dec 11, 2014·World Journal of Clinical Oncology·Shiro Koizume, Yohei Miyagi
May 18, 2018·Blood·Michael U CallaghanSteven W Pipe
Feb 14, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Steven P Grover, Nigel Mackman
Nov 26, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Alan E Mast
Nov 16, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Paul E R ElleryAlan E Mast
Jun 26, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Randal WestrickUNKNOWN Early Career Committee
Nov 20, 2018·Journal of Thrombosis and Haemostasis : JTH·T J GirardG J Broze
Dec 19, 2018·Blood·Angela C Weyand, Steven W Pipe
Mar 16, 2019·Current Protocols in Mouse Biology·Marisa A BrakeRandal J Westrick
Mar 31, 2019·Journal of Thrombosis and Haemostasis : JTH·Jose A DiazBrajesh K Lal
Jul 25, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Sunita Patel-HettDonald F Brophy
Oct 15, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Paul E R ElleryAlan E Mast
Jul 31, 2020·Journal of Thrombosis and Haemostasis : JTH·Amy E Siebert, Alan E Mast
Feb 23, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Jose A DiazBrajesh K Lal
Jan 23, 2018·Research and Practice in Thrombosis and Haemostasis·Paul E R ElleryAlan E Mast
Jul 28, 2019·Journal of Thrombosis and Haemostasis : JTH·James T B CrawleyIsabelle I Salles-Crawley
Feb 27, 2021·Seminars in Thrombosis and Hemostasis·Aisling M RehillUNKNOWN iPATH Study Group
Dec 18, 2019·Molecular Therapy : the Journal of the American Society of Gene Therapy·John S S ButterfieldRadoslaw Kaczmarek

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