A recombinant fragment of von Willebrand factor reduces fibrin-rich microthrombi formation in mice with endotoxemia.

Thrombosis Research
Trung C NguyenM A Cruz

Abstract

Disseminated fibrin deposition in the microvasculature such as in disseminated intravascular coagulation (DIC) arises from uninhibited activated coagulation secondary to sustained systemic inflammation. Currently there is no treatment for DIC. Treating the underlying trigger and supportive care are the current recommendations to manage DIC. This study aims at using recombinant von Willebrand factor (VWF) A2 domain polypeptide to inhibit VWF-mediated platelet adhesion to fibrin and prevent DIC. We use flow chamber assay to test the capacity of purified A2 protein to inhibit platelet adhesion to immobilized fibrin(ogen) and platelet-fibrin clot formation. We use a murine model of lipopolysaccharide-induced DIC to examine the effect of A2 protein on DIC. The A2 protein blocked flow-dependent platelet adhesion to fibrin, delayed fibrin polymerization, and inhibited platelet-fibrin clot formation in vitro. The infusion of the purified A2 protein to the endotoxin-treated mice prevented fibrin-rich microthrombi formation in brain, lung, kidney, and liver. It also attenuated levels of inflammatory mediators, and markedly reduced mortality rates at 96hours. The A2 protein inhibited platelet interaction with fibrin(ogen). Furthermore, A2...Continue Reading

References

Oct 1, 1986·The Journal of Clinical Investigation·J LoscalzoR I Handin
Mar 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·S A Olexa, A Z Budzynski
Feb 1, 1993·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·S C EndenburgJ J Zwaginga
May 20, 1999·Chest·F StéphanA Flahault
Jul 13, 2000·Critical Care Medicine·S VanderschuerenH Bobbaers
Aug 2, 2000·Critical Care Medicine·E RintalaP Kotilainen
Jul 4, 2002·International Journal of Hematology·Nobuo AokiUNKNOWN CTC-111-IM Clinical Research Group
Jul 10, 2003·JAMA : the Journal of the American Medical Association·Edward AbrahamUNKNOWN OPTIMIST Trial Study Group
Mar 14, 2007·Lancet·Simon NadelUNKNOWN REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group
Dec 20, 2007·Critical Care Medicine·Satoshi GandoUNKNOWN Japanese Association for Acute Medicine Disseminated Intravascular Coagulation (JAAM DIC) Study Group
Sep 20, 2008·Intensive Care Medicine·Robinder G KhemaniChristopher J L Newth
Feb 27, 2009·Critical Care Medicine·Fabián JaimesAlvaro Muñoz
Apr 12, 2012·Blood·Yan-Feng ZhouTimothy A Springer
May 24, 2012·The New England Journal of Medicine·V Marco RanieriUNKNOWN PROWESS-SHOCK Study Group
Sep 28, 2012·Internal and Emergency Medicine·Marcel Levi, Tom van der Poll
Jan 11, 2013·Scientific Reports·Nirit Mor-VakninDavid M Markovitz

❮ Previous
Next ❯

Citations

Sep 28, 2015·Critical Care Clinics·Trung C NguyenJoseph A Carcillo
Sep 14, 2019·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·Jamie S PenkHeidi J Dalton
Sep 4, 2018·Frontiers in Medicine·Christian ValladolidMiguel A Cruz
Mar 17, 2020·Critical Care Clinics·Trung C Nguyen
May 27, 2020·Translational Research : the Journal of Laboratory and Clinical Medicine·Monica A BrayRolando E Rumbaut

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Related Papers

The American Journal of Medicine
R W ColmanJ D Minna
Nihon Ketsueki Gakkai zasshi : journal of Japan Haematological Society
T Itakura
Nihon rinsho. Japanese journal of clinical medicine
T Matsuda
Nihon rinsho. Japanese journal of clinical medicine
M Maki
© 2021 Meta ULC. All rights reserved