THROMBOSIS AND HEMOSTASIS Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide
نویسندگان
چکیده
Henrik Østergaard,1 Jais R. Bjelke,2 Lene Hansen,3 Lars Christian Petersen,1 Anette A. Pedersen,2 Torben Elm,3 Flemming Møller,3 Mette B. Hermit,3 Pernille K. Holm,1 Thomas N. Krogh,2 Jørn M. Petersen,2 Mirella Ezban,3 Brit B. Sørensen,1 Mette D. Andersen,2 Henrik Agersø,3 Haleh Ahmadian,2 Kristoffer W. Balling,1 Marie Louise S. Christiansen,1 Karin Knobe,4 Timothy C. Nichols,5 Søren E. Bjørn,1 and Mikael Tranholm3
منابع مشابه
LIM kinase-1 selectively promotes glycoprotein Ib-IX-mediated TXA2 synthesis, platelet activation, and thrombosis.
Current antithrombotic drugs have an adverse effect on bleeding, highlighting the need for new molecular targets for developing antithrombotic drugs that minimally affect hemostasis. Here we show that LIMK1(-/-) mice have defective arterial thrombosis in vivo but do not differ from wild-type mice with respect to bleeding time. LIMK1(-/-) mice show a selective defect in platelet activation induc...
متن کاملTHROMBOSIS AND HEMOSTASIS Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment
A long-acting factor VIII (FVIII) as a replacement therapy for hemophilia A would significantly improve treatment options for patients with hemophilia A. To develop a FVIII with an extended circulating half-life, but without a reduction in activity, we have engineered 23 FVIII variants with introduced surface-exposed cysteines to which a polyethylene glycol (PEG) polymer was specifically conjug...
متن کاملEvaluation of Normal Range of Bleeding Scores in Healthy Iranian Adults using the International Society on Thrombosis and Hemostasis Bleeding Assessment Tool
Background: Bleeding assessment tools are key components in the evaluation of patients suspicious for bleeding disorders. The exact determination of the normal ranges of ISTH-BAT (International Society on Thrombosis and Hemostasis –Bleeding Assessment Tool) in the healthy population is a crucial step for determining who needs to be referred for further coagulation laboratory examinations. We ai...
متن کاملFactor IXa-factor VIIIa-cell surface complex does not contribute to the basal activation of the coagulation mechanism in vivo.
We have infused recombinant factor VIIa into patients with hereditary factor VII deficiency with marked reductions in plasma concentrations of factor IX activation peptide (FIXP), factor X activation peptide (FXP), and prothrombin activation fragment F1+2. These investigations show substantial elevations in these markers of coagulation activation and thereby demonstrate that the factor VII-tiss...
متن کاملRituximab for Treatment of Hemophilia A with High-Responder Inhibitors
Background: The development of inhibitors is a complication factor replacement therapy in hereditary factor VIII deficiency. Several management options are available for the treatment of inhibitor. Rituximab, a monoclonal antibody against CD20, reduces inhibitor level in rare bleeding disorders. The aim of this study was to evaluate the effectiveness of rituximab in lowering or eliminating the ...
متن کامل