In vitro fibrinolysis after adding low doses of plasminogen activators and plasmin generation with and without oxidative inactivation of plasmin inhibitors in newborns and adults.
OBJECTIVE
The aim of this study was to investigate in vitro fibrinolysis after adding low doses of plasminogen activators and to determine the functional role of plasmin inhibitors in newborns and adults.


METHODS
We have studied the kinetics of in vitro fibrinolysis after adding low doses of urokinase (UK) and recombinant tissue plasminogen activator (rt-PA) by use of a microtiter clot lysis assay. Additionally, we have determined plasmin generation with and without oxidative inactivation of plasmin inhibitors in newborns and adults.


RESULTS
The 50% lysis time in the clot lysis assay correlated with the activator dose and was significantly shorter in newborns at rt-PA concentrations of < 0.21 microgram/ml. When UK was used as an activator, the 50% lysis time was slightly but significantly prolonged in newborns at concentrations of 140-200 IU/ml, whereas we could find lower values (non-significant) at 110 and 80 IU/ml. Plasmin generation after oxidative inactivation of plasmin inhibitors was significantly lower in newborns, even when compared with adult plasma, which was diluted 50%. However, in a physiological plasma milieu (containing natural inhibitors), there were no differences in plasmin generation when streptokinase (SK) was used as an activator and only minor differences when UK was used.


CONCLUSIONS
Our data indicate a more rapid clot lysis at low UK and rt-PA concentrations in newborns despite significantly reduced plasminogen levels. The results of the plasmin generation experiments suggest a diminished effect of plasmin inhibitors towards fetal plasmin, which raises an explanation for the concentration-related differences in the clot lysis assay. The experience with thrombolytic agents in newborns is limited. Most dosage regimens for thrombolytic therapy in children or adults consist of an initial bolus infusion, followed by low-dose continuous treatment. Based on the results of our clot lysis experiments, we think that especially the continuous infusion of plasminogen activators after bolus administration should not be enhanced in newborns compared to older children or adults.
Ries
M
M
Klinik mit Poliklinik für Kinder und Jugendliche, Universität Erlangen-Nürnberg, Germany.
Klinge
J
J
Rauch
R
R
Trusen
B
B
Zenker
M
M
Keuper
H
H
Harms
D
D
D000328:Adult; D002700:Chloramines / Q000737:chemistry; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis; D006801:Humans; D007231:Infant, Newborn; D010084:Oxidation-Reduction; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000008:administration & dosage*; D014105:Tosyl Compounds / Q000737:chemistry; D000979:alpha-2-Antiplasmin / Q000378:metabolism
D002700:Chloramines; D017395:Plasminogen Activator Inhibitor 1; D014105:Tosyl Compounds; D000979:alpha-2-Antiplasmin; C016300:chloramine-T; D010960:Plasminogen Activators; D005341:Fibrinolysin