Effects of low molecular weight heparins on fibrin polymerization and clot sensitivity to t-PA-induced lysis.
We have previously demonstrated that therapeutic concentrations of unfractionated heparin (UFH) impair fibrin polymerization leading to the formation of clots which are more sensitive to lysis induced by tissue plasminogen activator (t-PA). The aim of this study was to compare the effect of UFH with that of three different low molecular weight heparins (LMWHs) on clot sensitivity to t-PA-induced lysis. Labelled fibrin clots, prepared from plasma containing UFH, Fraxiparine, Reviparine, Enoxaparine or saline, were incubated in phosphate buffer containing t-PA (0.1 and 0.5 microgram/ml) and plasminogen (20 micrograms/ml). The extent of clot lysis was quantified by counting the residual radioactivity of the clots and by measuring D-dimer levels released into the medium. Fibrin polymerization and clot structure were evaluated by means of a turbidimetric assay and by electron microscopic scanning. Pre-incubation of plasma with 0.5 or 1.0 U/ml UFH resulted in a marked dose-dependent acceleration of lysis induced by 0.1 or 0.5 microgram/ml t-PA. In contrast, lysis rates induced by 0.5 microgram/ml t-PA were not modified by pre-incubation of plasma with LMWHs. When exposed to 0.1 microgram/ml t-PA clots formed from plasma containing 0.5-2 IU/ml of Fraxiparine, Reviparine and Enoxaparine showed only a minor increase in lysis rates compared to control clots. There was not a clear dose-response curve with LMWHs. Furthermore, lysis rates obtained with UFH-treated clots were always significantly higher than those seen with LMWHs-treated clots.(ABSTRACT TRUNCATED AT 250 WORDS)
Parise
P
P
Institute of Internal and Vascular Medicine, University of Perugia, Italy.
Morini
M
M
Agnelli
G
G
Ascani
A
A
Nenci
G G
GG
D001777:Blood Coagulation / Q000187:drug effects*; D017984:Enoxaparin / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D017762:Nadroparin / Q000494:pharmacology; D009391:Nephelometry and Turbidimetry; D011108:Polymers / Q000737:chemistry*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D017984:Enoxaparin; D005338:Fibrin Fibrinogen Degradation Products; D017762:Nadroparin; D011108:Polymers; C036309:fibrin fragment D; D005337:Fibrin; D006493:Heparin; D010959:Tissue Plasminogen Activator