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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2001-3-27
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pubmed:abstractText |
In buffer systems, heparin and low molecular weight heparin (LMWH) directly inhibit the intrinsic factor X-activating complex (intrinsic tenase) but have no effect on the prothrombin-activating complex (prothrombinase). Although chemical modification of LMWH, to lower its affinity for antithrombin (LA-LMWH) has no effect on its ability to inhibit intrinsic tenase, N-desulfation of LMWH reduces its activity 12-fold. To further explore the role of sulfation, hypersulfated LA-LMWH was synthesized (sLA-LMWH). sLA-LMWH is not only a 32-fold more potent inhibitor of intrinsic tenase than LA-LMWH; it also acquires prothrombinase inhibitory activity. A direct correlation between the extent of sulfation of LA-LMWH and its inhibitory activity against intrinsic tenase and prothrombinase is observed. In plasma-based assays of tenase and prothrombinase, sLA-LMWH produces similar prolongation of clotting times in plasma depleted of antithrombin and/or heparin cofactor II as it does in control plasma. In contrast, heparin has no effect in antithrombin-depleted plasma. When the effect of sLA-LMWH on various components of tenase and prothrombinase was examined, its inhibitory activity was found to be cofactor-dependent (factors Va and VIIIa) and phospholipid-independent. These studies reveal that sLA-LMWH acts as a potent antithrombin-independent inhibitor of coagulation by attenuating intrinsic tenase and prothrombinase.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anticoagulants,
http://linkedlifedata.com/resource/pubmed/chemical/Antithrombins,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Factor Xa,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosaminoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Periodic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfur,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboplastin,
http://linkedlifedata.com/resource/pubmed/chemical/cancer procoagulant,
http://linkedlifedata.com/resource/pubmed/chemical/metaperiodate
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9755-61
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11134031-Anticoagulants,
pubmed-meshheading:11134031-Antithrombins,
pubmed-meshheading:11134031-Binding Sites,
pubmed-meshheading:11134031-Blood Coagulation,
pubmed-meshheading:11134031-Buffers,
pubmed-meshheading:11134031-Cysteine Endopeptidases,
pubmed-meshheading:11134031-Cysteine Proteinase Inhibitors,
pubmed-meshheading:11134031-Dose-Response Relationship, Drug,
pubmed-meshheading:11134031-Factor Xa,
pubmed-meshheading:11134031-Glycosaminoglycans,
pubmed-meshheading:11134031-Heparin,
pubmed-meshheading:11134031-Humans,
pubmed-meshheading:11134031-Inhibitory Concentration 50,
pubmed-meshheading:11134031-Kinetics,
pubmed-meshheading:11134031-Neoplasm Proteins,
pubmed-meshheading:11134031-Partial Thromboplastin Time,
pubmed-meshheading:11134031-Periodic Acid,
pubmed-meshheading:11134031-Phospholipids,
pubmed-meshheading:11134031-Protein Binding,
pubmed-meshheading:11134031-Sulfur,
pubmed-meshheading:11134031-Thromboplastin,
pubmed-meshheading:11134031-Time Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Hypersulfated low molecular weight heparin with reduced affinity for antithrombin acts as an anticoagulant by inhibiting intrinsic tenase and prothrombinase.
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pubmed:affiliation |
Hamilton Civic Hospitals Research Centre and Department of Medicine, McMaster University, Hamilton, Ontario L8V 1C3, Canada.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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