Document Detail


Inhibition of tissue factor pathway inhibitor (TFPI) by the aptamer BAX499 improves clotting of hemophiliac blood and plasma.
MedLine Citation:
PMID:  22632032     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI. Objectives: The aim of the study was to examine the concentration-dependent augmentation of clotting by BAX499. Methods: Whole blood clot formation was quantified by rotational thromboelastometry (ROTEM) and thromboelastography (TEG), thrombin generation in platelet poor plasma was assessed by the calibrated automated thrombogram (CAT) in samples from patients with congenital hemophilia A (N=55) and B (N=11), acquired hemophilia A (N=1), and healthy controls (N=37). Results: BAX499 significantly improved clotting of hemophilia patients in a concentration-dependent manner, resulting in clotting profiles in samples from severe hemophilia patients comparable to those of healthy controls. Conclusion: BAX499 improved ex vivo clotting parameters in blood and plasma from hemophilia A and B patients with different severity of disease and also in an acquired hemophilia patient. These results further support the contention that BAX499 may be an effective treatment for hemophilia patients, which is currently under investigation in clinical trials. © 2012 International Society on Thrombosis and Haemostasis.
Authors:
M E Gorczyca; S C Nair; B Jilma; S Priya; C Male; S Reitter; P Knoebl; J C Gilbert; R G Schaub; K E McGinness; I Pabinger; A Srivastava
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-26
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Affiliation:
Department of Clinical Pharmacology Department of Pediatrics and Adolescent Medicine Department of Medicine I, Clinical Division of Hematology and Hemostaseology, Medical University of Vienna Archemix Corporation, Cambridge, MA Baxter Healthcare Corporation, Cambridge, MA Department of Transfusion Medicine and Immuno-Hematology and Department of Hematology, Christian Medical College, Vellore, India.
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