Thrombolysis in Newborns and Infants

U. Nowak-Göttl; K. Auberger; S. Halimeh; R. Junker; J. Klinge; W. D. Kreuz; M. Ries; N. Schlegel

doi:10.1055/s-0037-1615566

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(S 01): 112-116
DOI: 10.1055/s-0037-1615566

Commentaries

Schattauer GmbH

Thrombolysis in Newborns and Infants

Authors

U. Nowak-Göttl

¹From the Departments of Paediatrics, University Children Hospital Münster
K. Auberger

²From the Departments of Paediatrics, University Children Hospital Munich
S. Halimeh

³From the Departments of Paediatrics, University Children Hospital Hanover
R. Junker

⁴Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, Germany
J. Klinge

⁵From the Departments of Paediatrics, University Children Hospital Erlangen
W. D. Kreuz

⁶From the Departments of Paediatrics, University Children Hospital Frankfurt
M. Ries

⁵From the Departments of Paediatrics, University Children Hospital Erlangen
N. Schlegel

⁷Biological Haematological Department, Hopital Robert Debré, Paris, France

Abstract

Summary

This review analyses literature reports from 1970 to 1998 assessing the use of streptokinase (SK), urokinase (UK) or recombinant tissuetype plasminogen activator (rt-PA) for thrombolytic therapy in neonates and infants. From 1970 to 1998 182 infants were reported to have received SK (n = 54; 29.5%), UK (n = 41; 22.5%) or rt-PA (n = 87; 48%). During thrombolytic therapy no concomitant heparin administration or low dose heparin therapy (5 U/kg/h) were recorded. To perform reocclusion prophylactics heparin was reinitiated at the end of thrombolytic therapy usually in the recommended dosage of 20 U/kg/h. The overall thrombolytic patency rate in neonates varied from 39% to 86%. Besides bleeding from local puncture sites or recent catheterisation sites (10.4%), pulmonary embolism was reported in 1.1% of the 182 infants. Major bleeding complications, i.e. pulmonary bleeding (0.6%), gastrointestinal bleeding (0.6%) or intraventricular haemorrhage (IVH 2.7%) are rarely reported side effects and only 2 thrombolysis related deaths due to haemorrhage were mentioned. Bleedings reported in the central nervous system (n = 4) mainly occurred in preterm infants (n = 3). In conclusion, data of this preliminary analysis suggest that there is no big difference (p = 0.09; χ²-test) in the efficacy rate between the 3 thrombolytic agents used in the first year of life. In each case an assessment must be made with respect to the relative benefit conferred by thrombolytic therapy in preventing organ or limb damage versus the potential side effects, costs and inconvenience for the childhood patient. Controlled prospective multicentre studies on thrombolytic therapy in neonates and infants are recommended to evaluate patency rates and adverse effects for the different thrombolytic agents used.

Key words

Thrombolysis - heparin - infancy - intracranial haemorrhage

Full Text

References

References
1 Andrew M. Developmental hemostasis: Relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74: 415-25.
2 Schmidt B, Andrew M. Neonatal thrombosis: Report of a prospective Canadian and International registry. Pediatrics 1995; 96: 939-43.
3 Nowak-Gottl U, Kries von R, Gobel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch Dis Child 1997; 76: F163-7.
4 Nowak-Gottl U, Koch HG, Aschka I, Kohlhase B, Vielhaber H, Kurle-mann G, Oleszuk-Raschke K, Kehl HG, Jurgens H, Schneppenheim R. Resistance to activated protein C (APCR) in children with venous or arterial thromboembolism. Brit J Haematol 1996; 92: 992-6.
5 Nowak-Gottl U, Dubbers A, Kececioglu D, Koch HG, Kotthoff S, Runde J, Vielhaber H. Factor V Leiden, protein C and lipoprotein (a) in catheter related thrombosis in childhood - a prospective study. J Pediatr 1997; 131: 608-12.
6 Andrew M, David M, Adams M, Ali K, Anderson R, Barnard D, Bernstein M, Brisson L, Cairney B, DeSai D, Grant R, Israels S, Jardine L, Luke B, Massicotte P, Silva M. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian registry of VTE. Blood 1994; 83: 1251-57.
7 Jobin J, O'Regan S, Demay G, Mongeau JG, Robitaille P. Neonatal renal vein thrombosis-long-term follow-up after conservative management. Clin Nephrol 1982; 17: 36-40.
8 Mocan H, Beattie TJ, Murphy AV. Renal venous thrombosis in infancy: long-term follow-up. Pediatr Nephrol 1991; 5: 45-9.
9 Keidan I, Lotan D, Gazit G, Boichis H, Reichman B, Linder N. Early neonatal renal venous thrombosis: long-term outcome. Acta Padiatr 1994; 83: 1225-7.
10 Nuss R, Hays T, Manco-Johnson M. Efficacy and safety of heparin anti-coagulation for neonatal renal vein thrombosis. J Ped Hematol Oncol 1994; 16: 127-31.
11 Prichard SL, Culham JAG, Rogers PJC. Low-dose fibrinolytic therapy in infants. J Pediatr 1985; 106: 594-8.
12 Wessel DL, Keane JF, Fellows KE, Robichand H, Lock JE. Fibrinolytic therapy for femoral arterial thrombosis after cardiac catherisation in infants and children. Am J Cardiol 1986; 58: 347-51.
13 Ino T, Benson LN, Freedom RM, Barker GA, Aipursky A, Rowe RD. Thrombolytic therapy for femoral artery thrombosis after pediatric cardiac catheterisation. Am Heart J 1988; 115: 633-9.
14 Brus F, Witsenburg M, Hofhuis WJD, Hazelzet JA, Hess J. Streptokinase treatment for femoral artery thrombosis after cardiac catheterisation in infants and children. Br Heart J 1990; 63: 291-4.
15 Zenz W, Muntean W, Beitzke A, Zobel G, Riccabona M, Gamillscheg A. Tissue plasminogen activator (alteplase) treatment for femoral artery thrombosis after cardiac catheterisation in infants and children. Br Heart J 1993; 70: 382-5.
16 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.
17 Ries M, Singer H, Hofbeck M, Klinge J, Wild F, Vogel P. Systemische und lokale Thrombolyse bei Kindern mit angeborenen Herzfehlern. Monatsschr Kinderheilkd 1994; 142: 205-8.
18 Vielhaber H, Kohlhase B, Koch HG, Kehl HG, Fliedner M, Kececioglu D, Kehrel B, Veltmann H, Vogt J, Nowak-Gottl U. Flush heparin during cardiac catheterization prevents long-term coagulations activation in children without APC-Resistance - preliminary results. Thromb Res 1996; 81: 651-6.
19 Delaplane D, Scott JP, Riggs TW, Silverman BL, Hunt CK. Urokinase therapy for a catheter-related right atrial thrombus. J Pediatr 1982; 100: 149-52.
20 Pongiglione G, Marasini M, Ribaldone D, Silvestri G, Tuo P, Garello-Cantoni L. Right atrial thrombosis in two premature infants: sucessful treatment with urokinase and heparin. Eur Heart J 1986; 7: 1086-9.
21 Zureikat GY, Martin GR, Silverman NH, Newth CJ. Urokinase therapy for a catheter-related right atrial thrombus and pulmonary embolism in a 2-month-old infant. Pediatr Pulmonol 1986; 2: 303-6.
22 Suarez CR, Ow EP, Lambert GH, Anderson CL, Purewal NS. Urokinase therapy for a central venous catheter thrombosis. Am J Hematol 1989; 31: 269-72.
23 Jolly N, Kaul UA, Khallilullah M. Right atrial thrombus over eustachian valves - sucessful lysis with streptokinase. Int J Cardiol 1991; 30: 354-6.
24 Overmeire van B, Reempts van PJ, Acker van 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.
25 Kehl HG, Kececioglu D, Vielhaber H, Kotthoff S, Weyand M, Jorch G, Vogt J, Nowak-Gottl U. Left atrial thrombus in a 10-month-old boy - successful thrombolysis with recombinant tissue-type plasminogen activator after open-heart surgery: review of the literature. Intensive Care Med 1996; 22: 968-71.
26 Bhat R, Fischer E, Doshi U, Raza S, Sepehri B, Flangigan P, Vidyasagar D. Neonatal abdominal aortic thrombosis. Crit Care Med 1981; 9: 858-61.
27 Rao S, Chow-Thug E, Flangigan D. Urokinase therapy in newborn infants with aortoiliac thrombosis. In: Mannucci DM, Dangelo A. eds. Urokinase: Basic and clinical aspects. Orlando, Fla: Academic Press 1982. p 215-21.
28 Corrigan Jr. JJ, Jeter M, Allen HD, Malone JM. Aortic thrombosis in a neonate: failure of urokinase thrombolytic therapy. Am J Pediatr Hematol Oncol 1982; 4: 243-7.
29 Le Blanc JG, Culham JA, Chan KW, Patterson MW, Tipple M, Sandor GG. Treatment of grafts and major vessel thrombosis with low dose strepto-kinase in children. Ann Thorac Surg 1986; 41: 630-5.
30 Vailas GN, Brouillette RT, Scott JP, Shkolnik A, Conway J, Wiringa K. Neonatal aortic thrombosis: Recent experience. J Pediatr 1986; 109: 101-8.
31 Emami A, Saidanha R, Knupp C, Kodroff M. Failure of systemic thrombolytic and heparin therapy in treatment of neonatal aortic thrombosis. Pediatrics 1987; 79: 773-7.
32 Kirk CR, Bhrolchain NC, Quereshi SA. Streptokinase for aortic thrombosis. Arch Dis Child 1988; 65: 1086-7.
33 Strife JL, Ball WS, Towbin R, Keller MS, Dillon T. Arterial occlusion in neonates: useof fibrinolytic therapy. Radiology 1988; 166: 395-00.
34 Reznik VM, Anderson J, Griswold WR, Segall ML, Murphy JL, Mendoza SA. Successful fibrinolytic treatment of arterial thrombosis and hypertension in a cocaine-exposed neonate. Pediatrics 1989; 84: 735-8.
35 Kennedy LA, Drummond WH, Knight ME, Millsaps MM, Williams JL. Successful treatment of neonatal aortic thrombosis with tissue plasminogen activator. J Pediatr 1990; 116: 798-801.
36 Ahluwalia JS, Kelsall AWR, Diederich S, Rennie JM. Successful treatment of aortic thrombosis after umbilical catheterization with tissue plasminogen activator. Acta Paediatr 1994; 83: 1215-7.
37 Berger C, Francoise M, Durand C, Sandre D, Gouyon JB. Utilisation de r activateur du plasminogene dans le traitment des thromboses aortiques du nouveau-ne. Arch Pediatr 1994; 1: 1014-8.
38 Deeg KH, Wolfel D, Rupprecht TH. Diagnosis of neonatal aortic thrombosis by colour coded Doppler sonography. Pediatr Radiol 1992; 22: 62-3.
39 Demarquez JL, Tavernier J, Babin JP. Thrombose de la veine renale chez le nouveau-ne. Arch Fr Pediatr 1975; 32: 381-8.
40 Velin P, Dupont D, Messa J, Kubar J. Thrombose veineuse renale bilate-rale neonatale et infection a Salmonella ibadan. Arch Fr Pediatr 1987; 44: 287-9.
41 Griffin MP, Casta A. Successful urokinase therapy for superior vena cava syndromes in a premature infant. Am J Dis Child 1986; 142: 267-8.
42 Rogers PCJ, Silva MP, Carter JEJ, Wadsworth LD. Renal vein thrombosis and response to therapy in a newborn due to protein C deficiency. Eur J Pediatr 1989; 149: 124-5.
43 Duncan BW, Adzick NS, Longaker MT, Edwards JR, Nelson RM, Koerper MA. In tero arterial embolism from renal vein thrombosis with successful postnatal thrombolytic therapy. J Ped Surg 1991; 26: 741-3.
44 Nowak-Gottl U, Schwabe D, Schneider W, Schlosser R, Kreuz W. Thrombolysis with recombinant tissue-type plasminogen activator in renal venous thrombosis. Lancet. 1992 340. 1105.
45 Farnoux C, Camard O, Pinquier D, Hurtaud-Roux MF, Sebag G, Schlegel N, Beaufils F. Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates. J Pediatr 1998; 133: 137-4.
46 Schmidt B, Wais U, Furste HO, Pringesheim W. Successful non-surgical treatment with urokinase and low-dose heparin. Helv Paediat Acta 1982; 37: 483-8.
47 Breviere GM, Vaksmann G, Francart C, Rey C, Dupuis C. Traitement par l'urokinase des thromboses arterielles systemiques du nouveau-ne. Arch Mal Coeur 1989; 82: 771-7.
48 Levy M, Benson LN, Burrows PS, Bentur Y, Strong DK, Smith J, Johnson D, Jacobson S, Koren G. Tissue plasminogen activator for the treatment of thromboembolism in infants and children. J Pediatr 1991; 118: 467-72.
49 Nowak-Gottl U, Kreuz WD, Schwabe D, Linde R, Kornhuber B. Thrombolysis with rt-PA in children suffering from arterial or venous thrombosis. Klin Padiatr 1991; 203: 359-62.
50 Doyle E, Britto J, Freemann J, Munro D, Morton NS. Thrombolysis with low dose tissue plasminogen activator. Arch Dis Child 1992; 67: 1483-4.
51 Rayan CA, Andrew M. Failure of thrombolytic therapy in four children with extensive thromboses. AJDC 1992; 146: 187-93.
52 Rehan VK, Cronin CMG, Bowman JM. Neonatal portal vein thrombosis successfully treated by regional streptokinase infusion. Eur J Pediatr 1994; 153: 456-9.
53 Gebara BM, Goetting MG, Wang AM. Dural sinus thrombosis complicating subclavian vein catheterization: treatment with local thrombolysis. Pediatrics 1995; 95: 138-40.
54 Wever MLG, Liem KD, Geven WB, Tank RB. Urokinase therapy in nenates with catheter related central venous thrombosis. Thromb Haemost 1995; 73: 180-5.
55 Schwabe D, Schlosser R, Auberger K, Kries von R, Nowak-Gottl U. Thrombolyse bei Neugeborenen und Sauglingen. Eine multizentrische Pilotstudie. Hamostaseologie 1996; 16: 236-8.
56 Weiner GM, Castle VP, DiPietro MA, Faix RG. Successful treatment of neonatal arterial thromboses with recombinant tissue plasminogen activator. J Pediatr 1998; 133: 133-6.
57 Andrew M, Michelson AD, Bovill E, Leaker M, Massicotte MP. Guidelines for antithrombotic therapy in pediatric patients. J Pediatr 1998; 123: 575-88.
58 Corrigan Jr. JJ, Sluth J, Jeter M, Lox C. Newborn's fibrinolytic mechanism: components and plasmin generation. Am J Hematol 1989; 32: 237-8.
59 Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68: 325-30.