title: Depolymerized holothurian glycosaminoglycan (DHG), a novel alternative anticoagulant for hemodialysis, is safe and effective in a dog renal failure model.
abstract: BACKGROUND
  Depolymerized holothurian glycosaminoglycan (DHG) is a new agent with anticoagulant properties quite different from those of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in terms of antithrombin III-dependency, and exerts an antithrombotic effect with less bleeding than UFH and LMWH in vivo. In this study, the anticoagulant and hemorrhagic effects of DHG were investigated on hemodialysis in a dog model of renal failure and compared with those of UFH, LMWH, and nafamostat mesilate (FUT).
  
  
  METHODS
  The dog renal failure model was prepared by 7/8 renal artery ligation. Effectiveness was based on completion of 3-hour hemodialysis, no marked clot deposition in the extracorporeal circuit, and permeability of blood urea nitrogen (BUN) and creatinine. Template bleeding was measured by determining the hemoglobin content of the blood from the wound.
  
  
  RESULTS
  DHG induced no major bleeding or clot formation during 3-hour hemodialysis, in contrast to UFH and LMWH, each of which induced marked bleeding. These glycosaminoglycans (GAGs) were equally effective in decreasing plasma levels of BUN and creatinine. On the other hand, dogs treated with FUT failed to complete 3-hour hemodialysis. These anticoagulants prolonged activated partial thromboplastin time (APTT) to different extents and GAGs prolonged thrombin clotting time markedly but FUT did not.
  
  
  CONCLUSIONS
  Our findings suggest that thrombin clotting time prolongation can contribute to prevention of clot formation in extracorporeal circuits, and the non-antithrombin III-dependent activities of DHG may be related to its low risk of hemorrhage for hemodialysis. DHG appears to be promising as an alternative anticoagulant with low risk of hemorrhage for hemodialysis.
authors.affiliation: Microbial Chemistry Research Foundation, Institute for Chemotherapy, Numazu, Shizuoka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Minamiguchi
authors.forename: Keiko T
authors.initials: KT
authors.lastname: Kitazato
authors.forename: Hideki
authors.initials: H
authors.lastname: Nagase
authors.forename: Eiji
authors.initials: E
authors.lastname: Sasaki
authors.forename: Katsuo
authors.initials: K
authors.lastname: Ohwada
authors.forename: Kenji
authors.initials: K
authors.lastname: Kitazato
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001772:Blood Cell Count; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006025:Glycosaminoglycans / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010314:Partial Thromboplastin Time; D006435:Renal Dialysis / Q000379:methods*; D051437:Renal Insufficiency / Q000628:therapy*; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D005230:Fatty Acids, Nonesterified; D006025:Glycosaminoglycans; C106156:depolymerized holothurian glucosaminoglycan