PMID- 15013278
OWN - NLM
STAT- MEDLINE
DCOM- 20040603
LR  - 20061115
IS  - 0049-3848 (Print)
IS  - 0049-3848 (Linking)
VI  - 112
IP  - 1-2
DP  - 2003
TI  - Prolonged bleeding time induced by anticoagulant glycosaminoglycans in dogs is 
      associated with the inhibition of thrombin-induced platelet aggregation.
PG  - 83-91
AB  - INTRODUCTION: The clinical use of unfractionated heparin (UFH) is complicated by 
      hemorrhage. This has led to a search for safer alternatives, one of which, the 
      recently identified depolymerized holothurian glycosaminoglycan (DHG), causes 
      less bleeding and exhibits a better antithrombotic-hemorrhagic ratio in rats and 
      dogs than UFH and low-molecular-weight heparin (LMWH). In contrast to UFH and 
      LMWH, which exert their anticoagulant effects by inhibiting thrombin in the 
      presence of antithrombin III (AT), DHG exerts its anticoagulant effect by 
      inhibiting the intrinsic factor Xase complex and thrombin in the presence of 
      heparin cofactor II (HCII). MATERIALS AND METHODS: The hemorrhagic effect of DHG 
      was compared with those of UFH and LMWH in healthy dogs, and the mechanism 
      responsible for prolonging bleeding time was examined both in dogs and with human 
      platelets. RESULTS: DHG prolonged template-bleeding time in dogs less than UFH 
      and LMWH do. Although the maximum noneffective concentrations of each 
      glycosaminoglycan (GAG) that prolong the bleeding time are almost the same as the 
      concentrations that inhibit thrombin-induced platelet aggregation, they are not 
      related to those that inhibit ADP-induced platelet aggregation. Results of 
      experiments on gel-filtered platelets from humans indicate that the inhibition of 
      thrombin-induced platelet aggregation caused by UFH and LMWH in the presence of 
      AT is more prominent than that caused by DHG with HCII. CONCLUSIONS: These 
      results suggest that the prolongation of bleeding time caused by GAGs are 
      associated with the inhibition of thrombin-induced platelet aggregation, and DHG 
      may cause less bleeding than UFH and LMWH because of its different thrombin 
      inhibition mechanism in platelet-rich plasma (PRP).
FAU - Kitazato, Kenji
AU  - Kitazato K
AD  - Cancer Research Laboratory, Hannno Research Center, Taiho Pharmaceutical, 1-27, 
      Misugidai, Hanno, Saitama, 357-8527, Japan. taiho.kitazato@nifty.ne.jp
FAU - Kitazato, Keiko T
AU  - Kitazato KT
FAU - Sasaki, Eiji
AU  - Sasaki E
FAU - Minamiguchi, Kazuhisa
AU  - Minamiguchi K
FAU - Nagase, Hideki
AU  - Nagase H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Anticoagulants)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 9005-49-6 (Heparin)
RN  - EC 3.4.21.5 (Thrombin)
SB  - IM
MH  - Animals
MH  - Anticoagulants/*pharmacology
MH  - Bleeding Time/*methods
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Glycosaminoglycans/*blood/*pharmacology
MH  - Heparin/*blood/*pharmacology
MH  - Heparin, Low-Molecular-Weight/pharmacology
MH  - Humans
MH  - Male
MH  - Platelet Aggregation/*drug effects
MH  - Thrombin/antagonists & inhibitors/*metabolism/pharmacology
EDAT- 2004/03/12 05:00
MHDA- 2004/06/04 05:00
CRDT- 2004/03/12 05:00
PHST- 2003/10/08 00:00 [received]
PHST- 2003/10/08 00:00 [revised]
PHST- 2003/10/09 00:00 [accepted]
PHST- 2004/03/12 05:00 [pubmed]
PHST- 2004/06/04 05:00 [medline]
PHST- 2004/03/12 05:00 [entrez]
AID - S0049384803005334 [pii]
AID - 10.1016/j.thromres.2003.10.005 [doi]
PST - ppublish
SO  - Thromb Res. 2003;112(1-2):83-91. doi: 10.1016/j.thromres.2003.10.005.