title: Novel design of peptides to reverse the anticoagulant activities of heparin and other glycosaminoglycans.
abstract: Patients undergoing anticoagulation with unfractionated heparin, low molecular weight heparin, or danaparoid may experience excess bleeding which requires reversal of the anticoagulant agent. Protamine is at present the only agent available for reversal of unfractionated heparin. Protamine is not effective in patients who have received low molecular weight heparin or danaparoid. We have developed a series of peptides based on consensus heparin binding sequences (Verrecchio et al., J Biol Chem 2000; 275: 7701-7707) that are capable of neutralizing the anti-thrombin activity of unfractionated heparin in vitro, the antifactor Xa activity of unfractionated heparin, Enoxaparin (Lovenox) and danaparoid (Orgaran) in vitro and the anti-Factor Xa activity of Enoxaparin in vivo in rats. These peptides may serve as alternatives for Protamine reversal of UFH and may be useful for neutralization of enoxaparin and danaparoid in humans.
authors: Cardeza Foundation for Hematologic Research, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA. barbara.schick@mail.tju.edu
authors: B P
authors: BP
authors: Schick
authors: J F
authors: JF
authors: Gradowski
authors: J D
authors: JD
authors: San Antonio
authors: J
authors: J
authors: Martinez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D001665:Binding Sites; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D016384:Consensus Sequence; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D015195:Drug Design; D017984:Enoxaparin / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D005170:Factor X / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D006493:Heparin / Q000008:administration & dosage; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D017984:Enoxaparin; D005170:Factor X; D006025:Glycosaminoglycans; D006493:Heparin; D006494:Heparin Antagonists; D006497:Heparan Sulfate; D010455:Peptides; D013917:Thrombin; C035838:danaparoid