Influence of soluble fibrin on reaction kinetics of plasmin type 1 and type 2 with alpha2-antiplasmin.
This study investigates, by slow binding kinetics methods, reaction kinetics of both plasmin types 1 and 2 with alpha -antiplasmin in the presence of increasing concentrations of either epsilon-amino-caproic acid (EACA) or soluble fibrin. All curves of plasmin-alpha -antiplasmin interaction followed the same pattern, indicating reversible slow binding inhibition with an initial loose complex and a following tight complex. Without soluble fibrin or EACA, differences between plasmin types 1 and 2 could be seen in the initial loose complex formation. The presence of increasing concentrations of EACA slowed down the first step of the reaction (without any effect on the second step), resulting in increasing values for K. Plasmin type 1 demonstrated a steep slope of K at an EACA concentration of 1 mmol/l. In plasmin type 2, the increase of K started at higher EACA concentrations. The value for K at a high EACA concentration (100 mmol/l) was the same for both plasmin types. In contrast to EACA, increasing concentrations of soluble fibrin slowed down both reaction steps. At high concentrations of soluble fibrin, the inhibitory effect of alpha -antiplasmin was almost completely abolished. Our data demonstrate that the effect of soluble fibrin and the lysine analogue EACA on plasmin-antiplasmin reactions are different and that the use of lysine analogues does not mimic fibrin in laboratory analyses of plasmin inhibition. In addition, our data indicate theoretical differences between plasmin type 1 and plasmin type 2, when used for local thrombolytic therapy.(2) (2) (i initial) (i initial) (i initial) (i initial) (2)
Ries
Martin
M
Clinic for Paediatric and Adolescent Medicine, Memmingen, Germany. dr.ries@kinderklinik-memmingen.de
Zenker
Martin
M
D000328:Adult; D015119:Aminocaproic Acid / Q000494:pharmacology; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000494:pharmacology*; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011485:Protein Binding / Q000187:drug effects; D012995:Solubility; D000979:alpha-2-Antiplasmin / Q000378:metabolism* / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism
D000979:alpha-2-Antiplasmin; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D005337:Fibrin; D005341:Fibrinolysin; D015119:Aminocaproic Acid