Thrombolytic Therapy in Children- Clinical Experiences with Recombinant Tissue-Plasminogen Activator

ABSTRACT

For the improvement of thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA) in children, more clinical data are needed. We retrospectively analyzed the clinical course of 20 patients (age ranging from 1 day to 16 years) with venous thrombosis (n = 16), arterial thrombosis (n = 2), and purpura fulminans by meningococcosis (n = 2). The venous thromboses were localized in the iliac-femoral veins (n = 9), brachiocephalic-jugular-subclavian veins (n = 6), and the superior caval vein (n = 1). The arterial occlusions were localized in the abdominal aorta and in the left pulmonary artery. Central venous catheters were of pathogenetic importance in seven cases. The patients were treated with rt-PA for 3 hours to 13 days. The dose ranged between 0.2 and 0.5 mg/kg for the initial bolus and 1.0 to 2.0 mg/kg/d for the continuous infusion. Nineteen patients received simultaneously low-dose unfractionated heparin. Complete clot lysis was detected in 11 cases, a partial lysis in 1, and in 8 patients thrombolytic therapy was not successful. An episode of hematemesis in one patient represented the only serious side effect observed in our study. A systemic decrease in fibrinogen concentration was also rare. In conclusion, thrombolysis with rt-PA represents an effective and safe therapy for children at the dosage used.

KEYWORD

Thrombosis - meningococcosis - thrombolysis - rt-PA - children

REFERENCES

• 1 Nowak-Göttl U, Auberger K, Halimeh S. Thrombolysis in newborns and infants.  Thromb Haemost . 1999;  112-116 (112-116)
• 2 Chalmers E A, Gibson B ES. Thrombolytic therapy in the management of paediatric thromboembolic disease.  Br J Haematol . 1999;  104 14-21
• 3 Collen D, Lijnen H R. Recent developments in thrombolytic therapy.  Fibrinolysis Proteolysis . 2000;  14 66-72
• 4 Leaker M, Massicotte M P, Brooker L A, Andrew M. Thrombolytic therapy in paediatric patients.  Thromb Haemost . 1996;  76 132-134
• 5 Manco-Johnson M J, Nuss R, Hays T. Combined thrombolytic and anticoagulant therapy for venous thrombosis in children.  J Pediatr . 2000;  136 446-453
• 6 Wever M LG, Liem K D, Geven W B, Tanke R B. Urokinase therapy in neonates with catheter related central venous thrombosis.  Thromb Haemost . 1995;  73 180-185
• 7 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry.  Pediatrics . 1995;  96 939-943
• 8 Wermes C, von Depka Prondzinski M, Lichtinghagen R. Clinical relevance of genetic risk factors for thrombosis in paediatric oncology patients with central venous catheters.  Eur J Pediatr . 1999;  S143-S146 (S143-S146)
• 9 Knöfler R, Siegert E, Lauterbach I. Clinical importance of prothrombotic risk factors in pediatric patients with malignancy-impact of central venous lines.  Eur J Pediatr . 1999;  S147-S150 (S147-S150)
• 10 De Mattia D, Penza R, Giordano P. Thromboembolic risk in children with nephrotic syndrome.  Haemostasis . 1991;  21 300-304
• 11 Citak A, Emre S, Sairin A, Bilge I, Nayir A. Hemostatic problems and thromboembolic complications in nephrotic children.  Pediatr Nephrol . 2000;  14 138-142
• 12 Zenz W, Bodo Z, Zobel G, Fanconi S, Rettenbacher A. Recombinant tissue plasminogen activator restores perfusion in meningococcal purpura fulminans.  Crit Care Med . 1998;  26 969-971
• 13 Veldman A, Ehrenberg A, Jager G. Is recombinant tissue plasminogen activator an option in the treatment of meningococcus-induced purpura?.  Crit Care Med . 2000;  28 598-600
• 14 Nowak-Göttl U, Kreuz W D, Schwabe D, Linde R, Kornhuber B. Thrombolysis with rt-PA in children suffering from arterial or venous thrombosis.  Klin Pädiatr . 1991;  203 359-362
• 15 Dillon P W, Fox P S, Berg C J, Cardella J F, Krummel T M. Recombinant tissue plasminogen activator for neonatal and pediatric vascular thrombolytic therapy.  J Pediatr Surg . 1993;  28 1264-1269
• 16 Anderson B J, Keeley S R, Johnson D. Caval thrombolysis in neonates using low doses of recombinant human tissue-type plasminogen activator.  Anaesth Intensive Care . 1991;  19 22-27
• 17 Varnholt V, Ringe H, Nietsch L, Gaedicke G. Hematothorax under thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in a 16-year-old girl.  Eur J Pediatr . 1999;  S140-S142 (S140-S142)
• 18 Zenz W, Arlt F, Sodia S, Berghold A. Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the literature of the last thirty years.  Semin Thromb Hemost . 1997;  23 321-332