PMID- 12631372 OWN - NLM STAT- MEDLINE DCOM- 20031217 LR - 20101118 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 63 IP - 4 DP - 2003 Apr TI - Depolymerized holothurian glycosaminoglycan (DHG), a novel alternative anticoagulant for hemodialysis, is safe and effective in a dog renal failure model. PG - 1548-55 AB - 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. CONCLUSION: 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. FAU - Minamiguchi, Kazuhisa AU - Minamiguchi K AD - Microbial Chemistry Research Foundation, Institute for Chemotherapy, Numazu, Shizuoka, Japan. FAU - Kitazato, Keiko T AU - Kitazato KT FAU - Nagase, Hideki AU - Nagase H FAU - Sasaki, Eiji AU - Sasaki E FAU - Ohwada, Katsuo AU - Ohwada K FAU - Kitazato, Kenji AU - Kitazato K LA - eng PT - Journal Article PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Anticoagulants) RN - 0 (Fatty Acids, Nonesterified) RN - 0 (Glycosaminoglycans) RN - 0 (depolymerized holothurian glucosaminoglycan) SB - IM MH - Animals MH - Anticoagulants/*pharmacology MH - Blood Cell Count MH - Blood Coagulation/drug effects MH - Disease Models, Animal MH - Dogs MH - Fatty Acids, Nonesterified/blood MH - Glycosaminoglycans/blood/*pharmacology MH - Male MH - Partial Thromboplastin Time MH - Renal Dialysis/*methods MH - Renal Insufficiency/*therapy MH - Thrombin Time EDAT- 2003/03/13 04:00 MHDA- 2003/12/18 05:00 CRDT- 2003/03/13 04:00 PHST- 2003/03/13 04:00 [pubmed] PHST- 2003/12/18 05:00 [medline] PHST- 2003/03/13 04:00 [entrez] AID - S0085-2538(15)49034-9 [pii] AID - 10.1046/j.1523-1755.2003.00879.x [doi] PST - ppublish SO - Kidney Int. 2003 Apr;63(4):1548-55. doi: 10.1046/j.1523-1755.2003.00879.x.