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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1356-1363. Prepublished online as a Blood First Edition Paper on October 30, 2003October 23, 2003; DOI 10.1182/blood-2003-07-2334. This Article Full Text (PDF) All Versions of this Article: 2003-07-2334v1 2003-07-2334v2 103/4/1356    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schick, B. P Articles by San Antonio, J. D Search for Related Content PubMed PubMed Citation Articles by Schick, B. P Articles by San Antonio, J. D Social Bookmarking                   What's this? Submitted July 10, 2003 Accepted October 16, 2003 Novel concatameric heparin-binding peptides reverse heparin and low molecular weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo Barbara P Schick*, David Maslow, Adrianna Moshinksi, and James D San Antonio Department of Medicine/Cardeza Foundation for Hematologic Research, Thomas Jefferson University, Philadelphia, PA, USA * Corresponding author; email: barbara.schick{at}jefferson.edu. Patients given unfractionated heparin (UFH) or low molecular weight heparin (LMWH) for prophylaxis or treatment of thrombosis sometimes suffer serious bleeding. We showed previously that peptides containing three or more tandem repeats of heparin-binding consensus sequences have high affinity for LMWH and neutralize LMWH (enoxaparin) in vivo in rats and in vitro in citrate. We have now modified the (ARKKAAKA)n tandem repeat peptides by cyclization or by inclusion of hydrophobic tails or cysteines to promote multimerization. These peptides exhibit high affinity binding to LMWH (Kds approx.50nM), similar potencies in neutralizing anti-Factor Xa activity of UFH and enoxaparin added to normal plasma in vitro, and equivalent or greater efficacy than Protamine. The peptide (ARKKAAKA)3VLVLVLVL was most effective in all plasmas from enoxaparin-treated patients, and was 4-20-fold more effective than Protamine. Several other peptide structures were effective in some patients' plasmas. All high-affinnity peptides reversed inhibition of thrombin-induced clot formation by UFH. These peptides (1 mg/300 gm rat) neutralized 1U/ml anti-Factor Xa activity of enoxaparin in rats within 1-2 min. Direct blood pressure and heart rate measurements showed little or no hemodynamic effect. These heparin-binding peptides, singly or in combination, are potential candidates for clinical reversal of UFH and LMWH in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Schuksz, M. M. Fuster, J. R. Brown, B. E. Crawford, D. P. Ditto, R. Lawrence, C. A. Glass, L. Wang, Y. Tor, and J. D. Esko Surfen, a small molecule antagonist of heparan sulfate PNAS, September 2, 2008; 105(35): 13075 - 13080. [Abstract] [Full Text] [PDF]

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