Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking.

Blood
James R ByrnesAlisa S Wolberg

Abstract

Factor XIII(a) [FXIII(a)] stabilizes clots and increases resistance to fibrinolysis and mechanical disruption. FXIIIa also mediates red blood cell (RBC) retention in contracting clots and determines venous thrombus size, suggesting FXIII(a) is a potential target for reducing thrombosis. However, the mechanism by which FXIIIa retains RBCs in clots is unknown. We determined the effect of FXIII(a) on human and murine clot weight and composition. Real-time microscopy revealed extensive RBC loss from clots formed in the absence of FXIIIa activity, and RBCs exhibited transient deformation as they exited the clots. Fibrin band-shift assays and flow cytometry did not reveal crosslinking of fibrin or FXIIIa substrates to RBCs, suggesting FXIIIa does not crosslink RBCs directly to the clot. RBCs were retained in clots from mice deficient in α2-antiplasmin, thrombin-activatable fibrinolysis inhibitor, or fibronectin, indicating RBC retention does not depend on these FXIIIa substrates. RBC retention in clots was positively correlated with fibrin network density; however, FXIIIa inhibition reduced RBC retention at all network densities. FXIIIa inhibition reduced RBC retention in clots formed with fibrinogen that lacks γ-chain crosslinking s...Continue Reading

References

Dec 1, 1975·Biochemical and Biophysical Research Communications·L LorandT L Steck
Jul 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·A Dutton, S J Singer
Dec 8, 1972·Annals of the New York Academy of Sciences·L LorandA Gray
Aug 23, 1984·The New England Journal of Medicine·L WilhelmsenG Tibblin
Oct 16, 1999·British Journal of Haematology·M LakP M Mannucci
Nov 5, 1999·Biophysical Journal·E A RyanL Lorand
Jun 14, 2002·FEBS Letters·David Lominadze, William L Dean
Sep 10, 2003·Chembiochem : a European Journal of Chemical Biology·Ching-Hsuan TungRalph Weissleder
Oct 3, 2003·Journal of Thrombosis and Haemostasis : JTH·E A te VeldeJ C M Meijers
Jun 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jean-Philippe ColletJohn W Weisel
Dec 15, 2005·British Journal of Haematology·Alisa S WolbergMaureane Hoffman
Jan 9, 2007·Blood Reviews·Alisa S Wolberg
Apr 2, 2010·Lab on a Chip·Xin M LiangNathan J Sniadecki
Feb 18, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Susan T Lord
Jul 12, 2011·Physiological Reviews·László MuszbekÉva Katona
Jan 10, 2012·Biophysical Journal·Christine C HelmsMartin Guthold
Nov 2, 2012·American Journal of Hematology·Robert S FrancoRobert M Cohen
Jun 1, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Maria M AlemanAlisa S Wolberg
Aug 10, 2013·Seminars in Thrombosis and Hemostasis·Verena Schroeder, Hans P Kohler
Nov 23, 2013·Journal of Thrombosis and Haemostasis : JTH·E L HethershawH Philippou
Jan 17, 2014·Thrombosis and Haemostasis·Cédric DuvalRobert A S Ariëns
Jan 21, 2014·The Journal of Biological Chemistry·Camilla Lund NikolajsenCarsten Scavenius
Jul 2, 2014·The Journal of Clinical Investigation·Maria M AlemanAlisa S Wolberg
Aug 22, 2014·Journal of Thrombosis and Haemostasis : JTH·N A KurniawanG H Koenderink
Sep 3, 2014·The Journal of Clinical Investigation·Yiming WangHeyu Ni
Jan 1, 2015·Nature Reviews. Disease Primers·Alisa S WolbergNigel Mackman

❮ Previous
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Citations

Feb 6, 2016·Journal of Thrombosis and Haemostasis : JTH·Lawrence F Brass, Scott L Diamond
Feb 13, 2016·Current Opinion in Hematology·Yiming WangHeyu Ni
Aug 1, 2016·La Presse médicale·Richard O Francis, Steven L Spitalnik
Nov 4, 2016·Thrombosis and Haemostasis·Rolf P KreutzJeffrey A Breall
Nov 24, 2016·Hämostaseologie·James R Byrnes, Alisa S Wolberg
Feb 17, 2018·Blood·Nathan J White
Jul 15, 2018·Journal of Thrombosis and Haemostasis : JTH·D MajiM A Suster
Aug 5, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Michel W J SmeetsPeter L Hordijk
Feb 24, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Marcus LehmannKeith B Neeves
Aug 25, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Scott L Diamond
Feb 24, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Sravya KattulaAlisa S Wolberg
Nov 30, 2018·Journal of Thrombosis and Haemostasis : JTH·J L Mitchell, N J Mutch
Jan 9, 2019·Journal of Thrombosis and Haemostasis : JTH·J W Weisel, R I Litvinov
Feb 19, 2019·Journal of Thrombosis and Haemostasis : JTH·Anna D ProtopopovaJohn W Weisel
Aug 16, 2017·Blood·James R Byrnes, Alisa S Wolberg
Oct 4, 2019·Journal of Thrombosis and Haemostasis : JTH·Ralf PasternackMartin Hils
Jan 29, 2020·Journal of Thrombosis and Haemostasis : JTH·Sravya KattulaAlisa S Wolberg
Nov 7, 2019·Journal of Neurointerventional Surgery·Andrew DouglasKaren Doyle
Jun 26, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Lori A HolleAlisa S Wolberg
Nov 21, 2018·Current Medicinal Chemistry·Daniel K Afosah, Rami A Al-Horani
Jun 21, 2017·BioMed Research International·Nathan E Hudson
Apr 24, 2019·Research and Practice in Thrombosis and Haemostasis·Marlien Pieters, Alisa S Wolberg
Oct 3, 2019·Haemophilia : the Official Journal of the World Federation of Hemophilia·Joan D Beckman, Alisa S Wolberg
Jan 29, 2020·Research and Practice in Thrombosis and Haemostasis·Zhaoming TangAlisa S Wolberg
Oct 29, 2017·Journal of Thrombosis and Haemostasis : JTH·J D BeckmanA S Wolberg
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Camille FaesRafal Pawlinski
Jul 27, 2018·Research and Practice in Thrombosis and Haemostasis·Wolfgang BergmeierHartmut Weiler
Aug 26, 2018·Haemophilia : the Official Journal of the World Federation of Hemophilia·Joan D BeckmanAlice D Ma
Mar 25, 2019·British Journal of Haematology·Roger J S PrestonJames S O'Donnell
May 2, 2017·ISBT Science Series·Rustem I Litvinov, John W Weisel
Jan 28, 2021·International Journal of Molecular Sciences·Martina LeitnerGary W Moore
Jan 12, 2021·Frontiers in Cardiovascular Medicine·Satish SinghGuy L Reed
Oct 1, 2018·Advanced Biosystems·Erin P SproulAshley C Brown
Apr 27, 2020·Analytical Biochemistry·Thomas SchmitzDiana Imhof
Jun 6, 2020·European Journal of Medicinal Chemistry·Rami A Al-Horani, Srabani Kar
Nov 2, 2020·Thrombosis and Haemostasis·Matthew Locke, Colin Longstaff
Apr 4, 2021·International Journal of Molecular Sciences·Fahad S M AlshehriNicola J Mutch

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