title: Soluble, cross-linked fibrin(ogen) hybrid oligomers do not stimulate t-PA conversion of plasminogen.
abstract: Cross-linked hybrid oligomers of fibrinogen and fibrin are found in plasma from fibrinaemic patients and normal individuals as well as in preparations of purified human fibrinogen. The present study was undertaken to see if such hybrid oligomers have the same stimulatory effect on tissue plasminogen activator (t-PA) conversion of plasminogen as do polymeric and monomeric fibrin. Hybrid oligomeric fibrin(ogen) material was provided by subjecting purified human fibrinogen to gel filtration in urea-containing buffer at pH 5.6. Well separated fractions of hybrid oligomeric material and monomeric fibrinogen were thus obtained. Some of this material was converted to soluble polymeric or monomeric fibrin using insolubilized thrombin. Hybrid polymeric fibrin, polymeric fibrin or monomeric fibrin were then added to citrated, normal plasma to 2.5 or 5 per cent of the plasma fibrinogen concentration. The added material was kept in solution by plasma fibrinogen. The "COA-SET Fibrin Monomer Test" (Kabi,Stocholm,Sweden), based on the ability of fibrin monomers to enhance t-PA mediated plasminogen-plasmin conversion, was used to compare the potential stimulatory effect of the preparations above. The results led to the following conclusions: 1) Cross-linked, soluble fibrin(ogen) hybrid polymers in a concentration of 5 per cent of plasma fibrinogen concentration (w/w) do not stimulate t-PA. 2) Thrombin conversion of the fibrin-fibrinogen hybrid material resulted in an increase in the rate of t-PA mediated plasminogen conversion, corresponding to the one observed with equivalent (w/w) amounts of fibrin monomers. Compared on a mole to mole basis, fibrin oligomers are more powerful than fibrin monomers as stimulators of t-PA activity.
authors.affiliation: Research Institute for Internal Medicine, University of Oslo, Rikshospitalet, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Grøn
authors.forename: A
authors.initials: A
authors.lastname: Bennick
authors.forename: C
authors.initials: C
authors.lastname: Filion-Myklebust
authors.forename: G R
authors.initials: GR
authors.lastname: Matsueda
authors.forename: W
authors.initials: W
authors.lastname: Nieuwenhuizen
authors.forename: F
authors.initials: F
authors.lastname: Brosstad
mesh_terms: D002850:Chromatography, Gel; D004347:Drug Interactions; D005176:Factor XIII / Q000378:metabolism; D005337:Fibrin / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D005341:Fibrinolysin / Q000096:biosynthesis; D006801:Humans; D010958:Plasminogen / Q000378:metabolism*; D011108:Polymers; D013917:Thrombin / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D011108:Polymers; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005176:Factor XIII; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin