Fibrin clots obtained from plasma containing heparin show a higher sensitivity to t-PA-induced lysis.
Although heparin is currently used in concomitance with thrombolytic agents to improve their efficacy, its effect on fibrinolysis is controversial. We have evaluated the sensitivity to t-PA-induced lysis of clots prepared from plasma preincubated in vitro with therapeutic concentrations of heparin. The extent of t-PA-induced lysis was significantly increased by preincubation of plasma with 0.5 and 1.0 U/ml heparin. The concentration of t-PA required to give similar lysis rates were reduced by up to five times after adding 1.0 U/ml heparin to plasma prior to clot formation. Heparin added to the t-PA-containing medium after clot formation did not exert any significant effect. The effect of heparin was not mediated by the inhibition of thrombin as preincubation of plasma with hirudin did not modify clot sensitivity to t-PA. We also found that heparin significantly modified fibrin assembly and clot structure as assessed by a turbidimetric assay. Pre-incubation of fibrinogen with heparin caused an increase in the speed of fibrin fibre polymerization and in the turbidity of the final fibrin gel; changes known to be associated with the formation of thicker fibrin fibres. Thus the effect of heparin on clot sensitivity to lysis appears to be due to an increased permeability of these clots to fibrinolytic components. This may contribute to the antithrombotic activity and to the haemorrhagic risk of heparin. These findings could be particularly important for clinical thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Nenci
G G
GG
Institute of Internal and Vascular Medicine, University of Perugia, Italy.
Parise
P
P
Morini
M
M
Rossini
A
A
Agnelli
G
G
D004357:Drug Synergism; D005337:Fibrin / Q000187:drug effects* / Q000302:isolation & purification; D005342:Fibrinolysis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D010949:Plasma / Q000187:drug effects; D013927:Thrombosis / Q000517:prevention & control; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D005337:Fibrin; D006493:Heparin; D010959:Tissue Plasminogen Activator