Lyse von Plasmagerinnseln nach Zugabe verschiedener Plasminogenaktivatoren in vitro

Zusammenfassung

Während bei Erwachsenen zahlreiche Studien zur Durchführung einer thrombo-lytischen Therapie publiziert wurden, gibt es für das Neugeborenenalter ver-gleichsweise wenig Daten. Intrauterin und in der Neonatalperiode zeigen sich sowohl bei der Gerinnung als auch bei der Fibrinolyse Unterschiede in der Konzen-tration und Funktion mehrerer Faktoren. Neben den Methoden zur Bestimmung von Einzelfaktoren haben globale Tests, z.B. zur Erfassung des gesamten fibri-nolytischen Potentials, nach wie vor große Bedeutung.

Wir berichten über die Befunde von Gerinnsel-Lysetests bei Neugeborenen verglichen mit Erwachsenen und diskutieren mögliche Auswirkungen dieser Befun-de auf Dosierungsrichtlinien einer thrombolytischen Therapie im Neugeborenen-alter.

Schlüsselwörter

Gerinnsel-Lysetest - Fibrinolyse - thrombolytische Therapie - Neugeborene

• LITERATUR

• 1 Anderson BJ, Keeley SR, Johnson ND. Ca-val thrombolysis in neonates using low doses of recombinant tissue-type plasminogen activator. Anaesth Intensive Care 1991; 19: 22-7.
• 2 Ambrus CM, Ambrus JL, Choi TS. et al. The fibrinolysin system and its relationship to disease in the newborn. Am J Pediatr Hema-tol Oncol 1979; 1: 251-60.
• 3 Andrew M, Brooker L, Leaker M. et al. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68: 325-30.
• 4 Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant. Am J Pediatr Hema-tol Oncol 1990; 12: 95-104.
• 5 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72: 1651-7.
• 6 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full term infant. Blood 1987; 70: 165-72.
• 7 Benavent A, Estellés A, Aznar J. et al. Dysfunctional plasminogen in full term newborn - Study of active site of plasmin. Thromb Haemost 1984; 51: 67-70.
• 8 Berger C, Francoise M, Durand C. et al. Utilisation de l'activateur tissulaire du plas-minogène (tPA) dans le traitement des thromboses aortiques du nouveau-né. Arch Pédiatr 1994; 1: 1014-8.
• 9 Brüster H, Pfitzner W. Untersuchungen über das fibrinolytische Potential bei reifgeborenen und jungen Säuglingen. Monatsschr Kinderheilkd 1964; 113: 476-81.
• 10 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-24.
• 11 Corrigan JJ. Neonatal thrombosis and the thrombolytic system: Pathophysiology and therapy. Am J Pediatr Hematol Oncol 1988; 10: 83-91.
• 12 Corrigan JJ, Sleeth JJ, Jeter MA, Lox CD. Newborn's fibrinolytic mechanism: Components and plasmin generation. Am J Hematol 1989; 32: 273-8.
• 13 Dillon PW, Fox PS, Berg CJ. et al. Recombinant tissue plasminogen activator for neonatal and pediatric vascular thrombolytic therapy. J Pediatr Surg 1993; 28: 1264-9.
• 14 Doyle E, Britto J, Freeman J. et al. Thrombolysis with low dose tissue plasminogen activator. Arch Dis Child 1992; 67: 1483-4.
• 15 Edelberg JM, Enghild JJ, Pizzo SV, Gonza-les-Gronow M. Neonatal plasminogen displays altered cell surface binding and activation kinetics. Correlation with increased gly-cosylation of the protein. J Clin Invest 1990; 86: 106-12.
• 16 Ekelund H. Fibrinolysis in the first year of life. Acta Paediatr Scand 1972; 61: 5-10.
• 17 Ekelund H, Hedner U, Astedt B. Fibrinolysis in human foetuses. Acta Paediatr Scand 1970; 59: 369-76.
• 18 Ekelund H, Hedner U, Nilsson IM. Fibrinolysis in newborns. Acta Paediatr Scand 1970; 59: 33-43.
• 19 Ekelund H, Finnström O. Fibrinolysis in preterm infants and in infants small for gestational age. Acta Paediatr Scand 1972; 61: 185-96.
• 20 Estelles A, Aznar J, Gilabert J, Parrilla JJ. Dysfunctional plasminogen in full-term newborn. Pediatr Res 1980; 14: 1180-5.
• 21 Guérin V, Boisseau MR. Efficiency of alte-plase in the treatment of venous and arterial thrombosis in neonates. Am J Hematol 1993; 42: 236-7.
• 22 Ishii A, Yamada S, Yamada R. et al. t-PA activity and antigen in the newborn and infant. J Perinat Med 1992; 20: 465-9.
• 23 Lecander I, Astedt B. Specific plasminogen activator inhibitor of placental type PAI 2 occurring in amniotic fluid and cord blood. J Lab Clin Med 1987; 110: 602-5.
• 24 Levi M, Roem D, Kamp AM. et al. Assessment of the relative contribution of different protease inhibitors to the inhibition of plasmin in vivo. Thromb Haemost 1993; 69: 141-6.
• 25 Ling X, Delorme M, Berry L. et al. Alpha 2-macroglobulin remains as important as anti-thrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces. Pediatr Res 1995; 37: 373-8.
• 26 Mackinnon S, Walker ID, Davidson JF, Walker JJ. Fibrinolytic activity in the healthy newborn infant at term. Fibrinolysis 1987; 1: 117-20.
• 27 Niederhoff H, Künzer W. Physiologie der Hämostase der Neugeborenen. Teil I. Monatsschr Kinderheilkd 1985; 133: 130-6.
• 28 Phillips LL, Skrodelis V. A comparison of the fibrinolytic enzyme system in maternal and umbilical cord blood. Pediatrics 1958; 20: 715-26.
• 29 Ries M, Klinge J, Rauch R. et al. 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. J Pediatr Hematol/Oncol 1996: 18 (im Druck)
• 30 Ries M, Klinge J, Rauch R. et al. Plasmin generation under physiological conditions and after oxidative inactivation of inhibitors. Evidence for a variation in kinetic behaviour between plasmin and alpha 2-antiplasmin in newborn infants. Thromb Haemost 1995; 73: 1296
• 31 Ries M, Singer H, Hofbeck M. Thrombolysis of a modified Blalock-Taussig shunt with recombinant tissue plasminogen activator in a newborn infant with pulmonary atresia and ventricular septal defect. Br Heart J 1994; 72: 201-2.
• 32 Ries M, Zenker M, Klinge J. et al. Age related differences in a clot lysis assay after adding different plasminogen activators in a plasma milieu in vitro. J Pediatr Hematol/ Oncol 1995; 17: 260-4.
• 33 Saleh AA, Hirokawa S, Stowers MA. et al. Effect of mode of delivery on certain parameters of neonatal hemostasis. Thromb Haemost 1993; 69: 1020
• 34 Seifried E, Transwell P, Ellbrück D. et al. Pharmacokinetics and haemostatic status during consecutive infusions of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction. Thromb Haemost 1989; 61: 497-501.
• 35 Seifried E, Transwell P, Rijken DC. et al. Pharmacokinetics of antigen and activity of recombinant tissue-type plasminogen activator after infusion in healthy volunteers. Drug Res 1988; 38: 418-22.
• 36 Ströder J, Künzer W. Gerinnungsstudien bei Kindern. VIII. Mitteilung. Ann paediat (Basel) 1957; 189: 198-204.
• 37 Suarez CR, Walenga J, Mangogna LC, Fareed J. Neonatal and maternal fibrinolysis: Activation at time of birth. Am J Hema-tol 1985; 19: 365-72.
• 38 Van Overmeire B, Van Reempts PJ, Van Acker KJ. Intracardiac thrombus formation with rapidly progressive heart failure in the neonate: treatment with tissue type plasminogen activator. Arch Dis Child 1992; 67: 443-5.