title: Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs.
abstract: Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations.
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Ana M F
authors.initials: AM
authors.lastname: Tovar
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Gustavo R C
authors.initials: GR
authors.lastname: Santos
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Nina V
authors.initials: NV
authors.lastname: Capillé
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Piquet
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Bianca F
authors.initials: BF
authors.lastname: Glauser
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Mariana S
authors.initials: MS
authors.lastname: Pereira
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vilanova
authors.affiliation: Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-913, Brazil.
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Mourão
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D002417:Cattle; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005944:Glucosamine / Q000031:analogs & derivatives / Q000737:chemistry*; D006487:Hemostasis; D006493:Heparin / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013552:Swine
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006493:Heparin; D005944:Glucosamine