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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
43
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pubmed:dateCreated |
1994-11-23
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pubmed:abstractText |
The effect of heparin and other glycosaminoglycans on the activation of factor X by the phospholipid membrane-bound human factor IXa-factor VIIIa complex (intrinsic fXase) was studied. Standard heparin inhibited purified intrinsic fXase by 50% at approximately 0.08 unit/ml (0.4 microgram/ml), which is below the normal range of heparin concentrations achieved during antithrombotic therapy (0.2-0.7 unit/ml). Kinetic and binding experiments revealed that heparin behaves as a partial noncompetitive inhibitor. The inhibition constant of heparin with low affinity for antithrombin was indistinguishable from heparin with high affinity for antithrombin (Ki = 20 nM). Additionally, "low molecular weight" heparin, which also is used as an antithrombotic drug, was a potent inhibitor of intrinsic fXase (Ki = 60 nM). Dermatan sulfate inhibited intrinsic fXase much more weakly than standard heparin (IC50 = 80 micrograms/ml). The IC50 of the other mammalian glycosaminoglycans, chondroitin sulfate, keratan sulfate, and hyaluronic acid, were greater than 100 micrograms/ml. Purified prothrombinase and extrinsic fXase were not inhibited by heparin. We propose that part of the antithrombotic action of heparin and low molecular weight heparin is due to anti-thrombin-independent inhibition of intrinsic fXase and that heparin with low affinity for antithrombin may be useful as an antithrombotic agent.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Blood Coagulation Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Factor IXa,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIIIa,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thromboplastin,
http://linkedlifedata.com/resource/pubmed/chemical/cancer procoagulant
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
269
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26796-800
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7929416-Blood Coagulation,
pubmed-meshheading:7929416-Blood Coagulation Factors,
pubmed-meshheading:7929416-Cysteine Endopeptidases,
pubmed-meshheading:7929416-Dose-Response Relationship, Drug,
pubmed-meshheading:7929416-Factor IXa,
pubmed-meshheading:7929416-Factor VIIIa,
pubmed-meshheading:7929416-Heparin,
pubmed-meshheading:7929416-Humans,
pubmed-meshheading:7929416-Models, Chemical,
pubmed-meshheading:7929416-Neoplasm Proteins,
pubmed-meshheading:7929416-Thromboplastin
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pubmed:year |
1994
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pubmed:articleTitle |
Inhibition by heparin of the human blood coagulation intrinsic pathway factor X activator.
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pubmed:affiliation |
Department of Medicine, Emory University, Atlanta, Georgia 30322.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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