Age-Related Differences in a Clot Lysis Assay After Adding Different Plasminogen Activators in a Plasma Milieu in Vitro

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Abstract
Purpose The fibrinolytic system is involved in a wide variety of biological phenomena and differs physiologically in newborns compared to older children or adults. Because the new born has hypoplasminogenemia and a possible existence of a dysfunctional plasminogen with normal adult levels of plasminogen activator inhibitor type 1 and α2-antiplasmin and elevated levels of plasminogen activator inhibitor type 2, it could be expected that the response to standard concentrations and doses of plasmonogen activators would be reduced. Patients and Methods We have studied the Kinetics of in vitro fibrinolysis after adding different concentrations of streptokinase(SK), urokinase (UK), and recombinant tissue plasminogen activator(rt-PA) by use of a microtiter clot lysis assay. Results Geometrical dilution rows showed characteristic dose response curves. After clot formation, a rapid lysis was seen with all plasminogen activators. The 50% lysis time correlated to the plasminogen activator dose and showed no diferences among normal adults, children aged 1–6 years, and children aged 7–14 years. Newborns demonstrated a significantly prolonged 50% lysis time with all urokinase concentrations. The 50% lysis time with recombinant tissue plasminogen activator and streptokinase was significantly prolonged only at high concentrations, whereas we could not see any differences at lower concentrations. Conclusion The experience with thrombolytic agents in newborns is limited, and no controlled investigations have been reported. Our results of the fibrinolytic potential in a plasma milieu in vitro after adding different plasminogen activators can be helpful to establish dosage guidelines for thrombolytic therapy in newborns and older children.

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