The Influence of Age on in vitro Plasmin Generation in the Presence of Fibrin Monomer

Abstract

Background and Objectives: The components of the fibrinolytic system interact to generate plasmin from its zymogen form, plasminogen. At birth, all the components of the fibrinolytic system are present but with differing plasma concentrations. The present study was undertaken to explore the effect of physiological, age-dependent factors of the fibrinolytic system during childhood on the capacity to generate plasmin. Design and Methods: Total plasmin generation was measured in venous plasma from umbilical cords and adults, on plastic and cell surfaces, in the presence of fibrin monomer, Desafib. Plasminogen, its inhibitors α₂-antiplasmin and plasminogen activator inhibitor type 1, and plasmin-α₂-antiplasmin complex in the time samples were assayed by enzyme-linked immunosorbent assay. The effect of addition of plasminogen on the plasmin generation in cord plasma and the effect of lipoprotein on adult and cord plasmin generation were measured. Results: On the surface of human umbilical vein endothelial cells, onset of plasmin generation was earlier (40 min) compared to plastic (60 min) but total plasmin generation was similar on both surfaces. The addition of plasminogen to cord plasma increased plasmin generation. Supplementation of lipoprotein in adult plasma had an inhibitory effect, but there was no significant effect in cord plasma. Interpretations and Conclusions: Plasmin generation is reduced in newborn compared to adult plasma. Decreased plasmin generation in cord plasma is likely due to decreased plasminogen concentration. The antifibrinolytic effect of lipoprotein is more pronounced in adults as compared to newborns due to the presence of higher plasminogen concentration.

Coagulation Testing in Pediatric Patients: The Young Are Not Just Miniature Adults

“…The antifibrinolytic effect of lipoproteins is also less pronounced in newborns compared with adults, due to the presence of lower plasminogen concentration. 37 When compared with adult reference ranges, children aged 1 to 5 years might display significantly higher values of soluble thrombomodulin, thrombin-antithrombin complex, and D-dimer. 38 Finally, although platelet function might be reduced in newborns, 39 the global primary hemostasis system, as assessed by the platelet function analyzer (PFA-100; Dade Behring, Marburg, Germany), might be enhanced because of the increased VWF-mediated platelet adhesion.…”

Engineering Ecotin for Identifying Proteins with a Trypsin Fold

“…Serine proteases possessing a trypsin fold are involved in many biological processes, including blood coagulation [1], metastasis of cancer cells [2], fibrinolysis [3], mammary gland involution [4], and the envenomation process [5]. These enzymes may be inhibited by ecotin, a periplasmic Escherichia coli-derived protein and a "fold-specific" inhibitor that has an unusually broad specificity to proteases such as trypsin, chymotrypsin, elastase, factor Xa, kallikrein, and factor XIIa [6,7].…”

Evaluation and Treatment of Neonatal Thrombus Formation in 17 Patients

“…8 Recently, it was shown that plasmin generation induced by r-tPA in vitro was lower in newborn than in adult plasma, which could explain the clinical finding that the elimination of thrombi in newborns is more challenging than in adults. 5 During the neonatal period, thrombin formation, endothelial activation, and procoagulant activity are increased. In our patients, catheter usage was 76.4%, but pathologies that increase the risk of thrombosis and lead to clinical deterioration, such as sepsis, hypoxia, polycythemia, and mutations in thrombosis markers, were also present.…”

“…In children, these systems exhibit agedependent differences, including a lower plasminogen concentration than in adults and thus reduced plasmin generation. 5 The varying risks of thrombus formation resulting from the above-described situations highlight the requirement for a patient-specific thrombolytic therapy in neonates and infants.…”