PMID- 9483172 OWN - NLM STAT- MEDLINE DCOM- 19980304 LR - 20180216 IS - 0301-0147 (Print) IS - 0301-0147 (Linking) VI - 27 IP - 4 DP - 1997 Jul-Aug TI - Neutralization of DHG, a new depolymerized holothurian glycosaminoglycan, by protamine sulfate and platelet factor 4. PG - 174-83 AB - The neutralization of depolymerized holothurian glycosaminoglycan (DHG), unfractionated heparin (UFH), and low-molecular-weight heparin (LMWH) by protamine sulfate (PS) or platelet factor 4 (PF4) was studied. In in vitro studies, the prolongation of thrombin clotting time (TCT) by these glycosaminoglycans was completely neutralized by PS, whereas activated partial thromboplastin time (APTT) was relatively resistant to neutralization. In rats, prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT ex vivo. Heparin-cofactor-II-dependent antithrombin activity of DHG or UFH was neutralized by PF4 at a high concentration to the same extent; however, prolongation of the APTT by DHG was more resistant to neutralization by PF4 at a physiological plasma level than that by UFH. In conclusion, since the prolongation of bleeding time by DHG was neutralized by PS with concomitant normalization of TCT, and since PF4 neutralized the antithrombin activity of DHG, these proteins may be useful as antidotes for DHG to prevent bleeding in case of an overdose. FAU - Sasaki, E AU - Sasaki E AD - Taiho Pharmaceutical Co., Ltd., Tokushima, Japan. FAU - Minamiguchi, K AU - Minamiguchi K FAU - Kitazato, K T AU - Kitazato KT FAU - Nagase, H AU - Nagase H FAU - Kitazato, K AU - Kitazato K LA - eng PT - Journal Article PL - Switzerland TA - Haemostasis JT - Haemostasis JID - 0371574 RN - 0 (Glycosaminoglycans) RN - 0 (Heparin Antagonists) RN - 0 (Heparin, Low-Molecular-Weight) RN - 0 (Protamines) RN - 0 (depolymerized holothurian glucosaminoglycan) RN - 37270-94-3 (Platelet Factor 4) RN - 81604-65-1 (Heparin Cofactor II) SB - IM MH - Animals MH - Bleeding Time MH - Drug Interactions MH - Glycosaminoglycans/*antagonists & inhibitors MH - Heparin Antagonists/pharmacology MH - Heparin Cofactor II/antagonists & inhibitors MH - Heparin, Low-Molecular-Weight/antagonists & inhibitors MH - Humans MH - Male MH - Partial Thromboplastin Time MH - Platelet Factor 4/*pharmacology MH - Protamines/*pharmacology MH - Rats MH - Rats, Wistar MH - Thrombin Time EDAT- 1997/07/01 00:00 MHDA- 1998/03/04 00:01 CRDT- 1997/07/01 00:00 PHST- 1997/07/01 00:00 [pubmed] PHST- 1998/03/04 00:01 [medline] PHST- 1997/07/01 00:00 [entrez] AID - 10.1159/000217453 [doi] PST - ppublish SO - Haemostasis. 1997 Jul-Aug;27(4):174-83. doi: 10.1159/000217453.