Zusammenfassung
Thrombembolien im Neugeborenenalter sind selten und werden vor allem im Zusammenhang
mit schweren Erkrankungen bzw. als Komplikation zentralvenöser oder arterieller Zugänge
beschrieben. Thrombosen der Arteria femoralis und der Arteria iliaca treten bei Kindern
als Komplikation nach Herzkatheteruntersuchung bzw. invasiver Blutdruckmessung über
die Arteria femoralis auf. Singuläre Nabelschnurarterien sind mit einer erhöhten Rate
chromosomaler Abberationen assoziiert, ein erhöhtes Risiko für thrombembolische Ereignisse
im Neugeborenen- und Säuglingsalter ist nicht beschrieben. Die Lysetherapie unter
Einsatz von rt-PA hat sich in kleineren Studien und bei Einzelpatienten bewährt, ist
aber für die Pädiatrie bisher nicht durch entsprechende Studien abgesichert.
Ein hypotrophes Frühgeborenes (29 + 6 Schwangerschaftswochen) erlitt am 5. postnatalen
Lebenstag einen arteriellen Verschluss der Beckenachse. Als Risikofaktoren wurden
ein hypoplastisches Gefäßbett bei aus der pränatalen Diagnostik bekannter gleichseitig
fehlender Arteria umbilicalis und Heterozygotie für die Prothrombin-G20210A-Mutation
gefunden. Nach Einsatz von rt-PA konnte eine Wiedereröffnung erreicht werden.
Im Falle eines drohenden Extremitäten- oder Organverlustes und Fehlen von absoluten
Kontraindikationen ist der Versuch einer Lysetherapie auch bei Früh- und Neugeborenen
gerechtfertigt. Da sich derartige Therapieversuche gegenwärtig noch von Erfahrungen
aus der Erwachsenenmedizin ableiten, wären weitere Studien zur Erforschung der Pharmakokinetik
und Dynamik von rt-PA im Neugeborenen- und Säuglingsalter wünschenswert.
Abstract
Thromboembolic events in neonates are very rare. They are often associated with severe
disease affecting the newborn or are secondary to central venous lines or arterial
catheters. Most of the described cases of thromboses of the iliac or femoral arteries
are associated with cardiac catheterisation or femoral invasive blood pressure monitoring.
The relationship between single umbilical arteries and an increased incidence of structural
and chromosomal anomalies is well known, but a higher rate of thromboembolic disease
in infants with single umbilical arteries has not been described. Rt-PA (recombinant
tissue plasminogen activator) has been successfully used in small studies and numerous
case reports. To date controlled clinical trials giving guidelines for antithrombotic
therapy using rt-PA are still lacking.
We report the clinical course of a 700 g premature male, who was born by Caesarean
section at 29 + 6 gestational weeks. On the fifth day the baby suffered from arterial
thrombosis of the right pelvis axis. Antenatally a single umbilical artery was identified.
Iliac arteries on the involved site appeared hypoplastic. Additionally, the prothrombin
G20210A mutation was found. The patient was treated successfully using recombinant
tissue plasminogen activator.
In the case of a high risk of limb or organ loss due to arterial thrombosis, thrombolysis
using rt-PA is justified. Appropriate rt-PA treatment has been studied for the adult
but not the paediatric population. Hence, well-designed clinical trials are necessary
to determine the pharmacokinetics and dynamics of thrombolytic agents in children.
Schlüsselwörter
Neonatologie - Thrombose - rt-PA - Lysetherapie - singuläre Nabelschnurarterie - Prothrombin-G20210A-Mutation
Key words
Neonatology - thrombosis - rt-PA - fibrinolysis - single umbilical artery - prothrombin
G20210A mutation
1 Andrew M E, Monagle P, deVeber G, Chan A K. Thromboembolic disease and antithrombotic
therapy in newborns. Hematology. Am Soc Hematol Educ Program 2001: 358-374
2
Kothari S S, Varma S, Wasir H S.
Thrombolytic therapy in infants and children.
Am Heart J.
1994;
127
651-657
3
Knofler R, Dinger J, Kabus M, Muller D, Lauterbach I, Rupprecht E, Taut-Sack H, Weissbach G.
Thrombolytic therapy in children - clinical experiences with recombinant tissue-plasminogen
activator.
Semin Thromb Hemost.
2001;
27
69-174
4
Torres-Valdivieso M J, Cobas J, Barrio C, Munoz C, Pascual M, Orbea C, Rodriguez E,
Gutierrez F.
Successful use of tissue plasminogen activator in catheter-related intracardiac thrombus
of a premature infant.
Am J Perinatol.
2003;
20
91-96
5
Richardson R, Applebaum H, Touran T, Franceschini R E, Robbie P A, Wirtschafter D D,
Taber P.
Effective thrombolytic therapy of aortic thrombosis in the small premature infant.
J Pediatr Surg.
1988;
23
1198-1200
6
Nowak-Göttl U, Auberger K, Halimeh S, Junker R, Klinge J, Kreuz W D, Ries M, Schlegel N.
Thrombolysis in newborns and infants.
Thromb Haemost.
1999;
82(Suppl1)
12-116
7
Michelson A D, Bovill E, Monagle P, Andrew M.
Antithrombotic therapy in children.
Chest.
1998;
114(Suppl)
748S-769S
8
Nowak-Göttl U, von Kries R, Gobel U.
Neonatal symptomatic thromboembolism in Germany: two year survey.
Arch Dis Child Fetal Neonatal Ed.
1997;
76
F163-F167
9
White R H.
The epidemiology of venous thromboembolism.
Circulation.
2003;
107(Suppl)
I4-18
10
Rosendaal F R, Doggen C J, Zivelin A, Arruda V R, Aiach M, Siscovick D S, Hillarp A,
Watzke H H, Bernardi F, Cumming A M, Preston F E, Reitsma P H.
Geographic distribution of the 20 210 G to A prothrombin variant.
Thromb Haemost.
1998;
79
706-708
11
Young G, Manco-Johnson M, Gill J C, Dimichele D M, Tarantino M D, Abshire T, Nugent D J.
Clinical manifestations of the prothrombin G20210A mutation in children: a pediatric
coagulation consortium study.
J Thromb Haemost.
2003;
1
958-962
12
Tripodi A, Chantarangkul V, Mannucci P M.
Hyperprothrombinemia may result in acquired activated protein C resistance [letter].
Blood.
2000;
96
3295-3296
13
Heifetz S A.
Single umbilical artery: a statistical analysis of 237 autopsy cases and review of
literature.
Perspect Pediatr Pathol.
1984;
8
345-378
14
Meyer W W, Lind J.
Iliac arteries in children with a single umbilical artery. Structure, calcifications,
and early atherosclerotic lesions.
Arch Dis Child.
1974;
49
671-679
15
Abuhamad A Z, Shaffer W, Mari G, Copel J A, Hobbins J C, Evans A T.
Single umbilical artery: does it matter which artery is missing?.
Am J Obstet Gynecol.
1995;
173
728-732
16
Geipel A, Germer U, Welp T, Schwinger E, Gembruch U.
Prenatal diagnosis of single umbilical artery: determination of the absent side, associated
anomalies, Doppler findings and perinatal outcome.
Ultrasound Obstet Gynecol.
2000;
15
114-117
17
Beverly J, Vincent R N.
Iliofemoral arterial malformation associated with single umbilical artery: implications
for interventional catheterization?.
Catheter Cardiovasc Interv.
2003;
59
268-270
18
De Catte L, Burrini D, Mares C, Waterschoot T.
Single umbilical artery: analysis of Doppler flow indices and arterial diameters in
normal and small-for-gestational age fetuses.
Ultrasound Obstet Gynecol.
1996;
8
27-30
19
Saller DN J r, Keene C L, Sun C C, Schwartz S.
The association of single umbilical artery with cytogenetically abnormal pregnancies.
Am J Obstet Gynecol.
1990;
163
922-925
20
Sepulveda W, Bower S, Flack N J, Fisk N M.
Discordant iliac and femoral artery flow velocity waveforms in fetuses with single
umbilical artery.
Am J Obstet Gynecol.
1994;
171
521-525
21
Berry C L, Gosling R G, Laogun A A, Bryan E.
Anomalous iliac compliance in children with a single umbilical artery.
Br Heart J.
1976;
38
510-515
22
Nowak-Göttl U, Kreuz W D, Schwabe D, Linde R, Kornhuber B.
Thrombolyse mit rt-PA bei Kindern mit arteriellen und venösen Thrombosen - ein neuer
Therapieansatz.
Klin Pädiatr.
1991;
203
359-362
23
Seibert J J, Northington F J, Miers J F, Taylor B J.
Aortic thrombosis after umbilical artery catheterization in neonates: prevalence of
complications on long term follow up.
Am J Roentgenol.
1991;
156
567-575
24
Hartmann J, Hussein A, Trowitzsch E, Becker J, Hennecke K H.
Treatment of neonatal thrombus formation with recombinant tissue plasminogen activator:
six years experience and review of the literature.
Arch Dis Child Fetal Neonatal Ed.
2001;
85
F18-22
25
Manco-Johnson M J, Grabowski E F, Hellgreen M, Kemahli A S, Massicotte M P, Muntean W,
Peters M, Schlegel N, Wang M, Nowak-Gottl U.
Recommendations for tPA thrombolysis in children. On behalf of the Scientific Subcommittee
on Perinatal and Pediatric Thrombosis of the Scientific and Standardization Committee
of the International Society of Thrombosis and Haemostasis.
Thromb Haemost.
2002;
88
157-158
26
Farnoux C, Camard O, Pinquier D, Hurtaud-Roux M F, Sebag G, Schlegel N, Beaufils F.
Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates.
J Pediatr.
1998;
133
137-140
27
Weiner G M, Castle V P, DiPietro M A, Faix R G.
Successful treatment of neonatal arterial thromboses with recombinant tissue plasminogen
activator.
J Pediatr.
1998;
133
133-136
28
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
Dr. Roland Haase
Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin
Martin-Luther-Universität Halle-Wittenberg
06097 Halle/Saale
Phone: 0345-5572500
Fax: 0345-5572389
Email: roland.haase@medizin.uni-halle.de