Abstract
Acquired thrombotic thrombocytopenic purpura (TTP) is caused by an autoantibody-mediated deficiency of the von Willebrand factor-cleaving protease ADAMTS-13. Acute episodes of the disease are treated with a combination of immunosuppression and repeated cycles of plasma exchange to remove anti-ADAMTS-13 autoantibodies and, at the same time, replenish functional ADAMTS-13. Although this is often effective, the mortality rate has remained between 10% and 20%, highlighting the need for safer treatment options. We previously showed that, in vitro, human recombinant ADAMTS-13 (rADAMTS-13) is able to override neutralizing antibodies and restore ADAMTS-13 activity in plasma from patients with acquired TTP. In the present study, we assessed the in vivo feasibility of this strategy by using a rat model. Wild-type rats were adjusted to an ADAMTS-13 inhibitor (inhibitor) titer of ~ 10 BU mL(-1) with goat anti-ADAMTS-13 IgG, and treated with increasing doses of rADAMTS-13. Blood samples were drawn and analyzed for ADAMTS-13-specific parameters, including FRETS-VWF73 activity, inhibitor, and ADAMTS-13-specific immune complexes (ICs). The pharmacokinetics of ADAMTS-13 activity and inhibitors were evaluated. Administration of inhibitor titer-a...Continue Reading
References
Aug 8, 1991·The New England Journal of Medicine·G A RockR A Spasoff
Dec 1, 1986·The Journal of Clinical Investigation·J L MoakeJ D Hellums
Nov 26, 1998·The New England Journal of Medicine·H M Tsai, E C Lian
Oct 5, 2001·Nature·G G LevyH M Tsai
Nov 7, 2001·Inhalation Toxicology·P E NewtonW E Rinehart
Jan 31, 2002·Annual Review of Medicine·Joel L Moake
Oct 24, 2002·Blood·Barbara PlaimauerFriedrich Scheiflinger
Jul 12, 2003·Blood·Friedrich ScheiflingerManfred Rieger
Jan 17, 2004·Seminars in Hematology·Koichi Kokame, Toshiyuki Miyata
Nov 4, 2004·British Journal of Haematology·Flora PeyvandiPier Mannuccio Mannucci
Apr 2, 2005·British Journal of Haematology·Koichi KokameToshiyuki Miyata
May 14, 2005·Blood·Manfred RiegerFriedrich Scheiflinger
Oct 4, 2005·The Journal of Clinical Investigation·David G MottoDavid Ginsburg
Dec 22, 2005·Blood·Fumiaki BannoToshiyuki Miyata
Aug 2, 2006·Journal of Thrombosis and Haemostasis : JTH·S G ShelatX L Zheng
Aug 13, 2008·Current Opinion in Hematology·Johanna A Kremer Hovinga, Sara C Meyer
May 14, 2009·Arthritis Research & Therapy·Louise E FullClaudia Monaco
Oct 23, 2009·Human Mutation·Luca A LottaFlora Peyvandi
Jun 17, 2010·Blood·Hendrik B FeysKaren Vanhoorelbeke
Aug 6, 2010·Blood·James N George
Feb 8, 2011·Journal of Thrombosis and Haemostasis : JTH·B PlaimauerF Scheiflinger
Apr 25, 2012·Blood·Alexandra SchivizEva-Maria Muchitsch
Mar 16, 2013·The Journal of Pharmacy and Pharmacology·Xue-Xi WangYong-Jie Wu
Nov 19, 2013·Haematologica·Silvia FerrariFriedrich Scheiflinger
Feb 18, 2014·Haematologica·Rana GrillbergerFriedrich Scheiflinger
Citations
Jul 3, 2016·Journal of Thrombosis and Haemostasis : JTH·A KopićW Höllriegl
Sep 16, 2017·Blood·Marie ScullyBruce Ewenstein
Jul 27, 2018·Research and Practice in Thrombosis and Haemostasis·Camila Masias, Spero R Cataland
Jul 15, 2018·Blood·Camila Masias, Spero R Cataland
Jul 31, 2019·Expert Opinion on Biological Therapy·Maëlle le BesneraisPaul Coppo
Aug 2, 2017·Current Opinion in Hematology·Yvette C TanhehcoAra Metjian
Sep 3, 2020·Expert Review of Hematology·Inés Gómez-SeguíJavier de la Rubia
May 10, 2017·Blood Advances·Liang ZhengX Long Zheng
Apr 7, 2017·Nature Reviews. Disease Primers·Johanna A Kremer HovingaKaren Vanhoorelbeke
Apr 4, 2020·Expert Review of Hematology·Andrés Gómez-De LeónDavid Gómez-Almaguer
Dec 19, 2020·Intensive Care Medicine Experimental·Mathijs R WirtzNicole P Juffermans
Jul 20, 2021·Expert Review of Hematology·Inés Gómez-SeguíJavier de la Rubia Comos
Sep 1, 2021·Transfusion clinique et biologique : journal de la Société française de transfusion sanguine·P Poullin