Neonatal Aortic Thrombosis: A Comprehensive Review

Abstract

Background: Neonatal aortic thrombosis is a rare occurrence, but can be fatal. Treatment of this condition is hampered by the lack of large studies involving this pediatric population. Reporting of this condition is also not standardized.

Methods: The purpose of this review is to collate available literature on the incidence, risk factors, presentation, treatment and outcome of neonatal aortic thrombosis as well as suggest a treatment model.

Results: A Medline search of PubMed, OVID and Cochrane databases was undertaken using the key words “neonatal”, “infant”, “aorta”, “aortic”, “thrombosis”, “thrombus” and “clot”. Limits were set for articles that were English language only and published between 1980 and September 2009. Following review of all articles using predetermined search words and criteria, 38 were found with sufficient data for our purpose. The reported total number of neonatal patients with aortic thrombosis was 148 and 78% of the aortic thromboses in this review were related to arterial umbilical catheterization.

Conclusions: We have suggested a classification system to standardize reporting of neonatal aortic thrombosis, as well as a treatment decision tree, and a clinical guide for the treatment of thrombosis in children. As always, clinicians should balance the risks and benefits of their decision to treat with the level of local expertise. This guide may specifically serve the neonatal population with line-related aortic thrombosis.

Zusammenfassung

Hintergrund: Neugeborenen-Aortenthrombosen sind seltenen, im klinischen Verlauf aber häufig tödlich. Die Behandlung dieser seltenen Erkrankung erfolgt individualisiert, da Studien fehlen.

Methoden: Der Zweck dieses Überblickes ist es, vorhandene Literatur zu sichten, Risikofaktoren zu evaluieren und ein Behandlungsmodell vorzustellen.

Ergebnisse: Eine Medline-Suche der Daten-banken PubMed, OVID und Cochrane wurde unter Verwendung der folgenden Schlüsselwörter aufgenommen; „neonatal”, „infant”, „aorta”, „aortic”, „thrombosis”, „thrombus” und „clot”. Artikel sollten in englische Sprache publiziert und zwischen 1980 und September 2009 veröffentlicht worden sein. Nach unseren Suchkriterien wurden 38 Fallberichte zu dieser Erkrankung gefunden. Die Gesamtzahl der neugeborenen Patienten mit Aortenthrombose betrug 148, und 78% der Aortenthrombosen in dieser Übersicht waren mit Nabelarterienkathetern assoziiert.

Zusammenfassungen: Wir haben ein Klassifizierungsverfahren entwickelt, um retrospektiv Fallberichte neonataler Aortenthrombosen sowie Behandlungskriterien zu standardisieren. Ziel war es, unter Abwägung von Nutzen und Risiko eine Behandlungsrichtlinie für diese Erkrankung der katheterassoziierten Aortenthrombose zur Verfügung zu stellen.

Key words

catheter associated thrombosis - neonatal aortic thrombosis - therapy - risk factors

Schlüsselwörter

katheterassoziierte Thrombose - neonatale Aortenthrombose - Therapie - Risikofaktoren

References

• 1 Alpert J, O’Donnell JA, Parsonnet V. et al . Clinically recognized limb ischemia in the neonate after umbilical artery catheterization.  Am J Surg. 1980 Sep;  140 413-418
• 2 Boo NY, Wong MC, Zulkifli SS. et al . Risk factors associated with umbilical vascular catheter-associated thrombosis in newborn infants.  J Pediatr Child Health. 1999;  35 460-465
• 3 Cheah FC, Boo NY, Rohana J. et al . Successful clot lysis using low dose of streptokinase in 22 neonates with aortic thromboses.  J Pediatr Child Health. 2001;  37 479-482
• 4 CHEST . Antithrombotic and thrombolytic therapy: American College of Chest Physicians evidence-based clinical practice guidelines (8^th edition).  2008;  133 67S-968S
• 5 Colburn M, Gelabert JA, Quinones-Baldrich W. Neonatal aortic thrombosis.  Surgery. 1992;  111 21-28
• 6 Corrigan JJ, Allen HD, Jeter M. et al . Aortic thrombosis in a neonate: failure of urokinase thrombolytic therapy.  Am J Pediatr Hematol Oncol. 1982;  4 243-247
• 7 DeGodoy JMP, DeMarchi CH, Silva MGF. et al . Thrombosis of the abdominal aorta in a newborn: case report and review of literature.  J Pediatr Surg. 2003;  38 E11-E12
• 8 Emami S, Saldanha R, Knupp C. et al . Failure of systemic thrombolytic and heparin therapy in the treatment of neonatal aortic thrombosis.  Pediatrics. 2007;  79 773-776
• 9 Giacoia GP. High-dose urokinase therapy in newborn infants with major vessel thrombosis.  Clin Pediatr (Phila). 1993;  32 231-237
• 10 Greenberg SB, Bhutta ST, Buchmann RF. Gadolinium-enhanced magnetic resonance angiography in neonates and infants suspected of caval or aortic thrombosis.  Pediatr Radiol. 2004;  34 948-951
• 11 Gupta AA. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children.  J Pediatr. 2001;  139 682-688
• 12 Hartmann J, Hussein A, Trowitzsch E. et al . 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-F22
• 13 Horgan MJ, Bartoletti A, Polansky S. et al . Effect of heparin infusates in arterial umbilical artery catheters on frequency of thrombotic complications.  J Pediatr. 1987;  111 774-778
• 14 Janssen DR, Ohmstede DP, Liske MR. et al . Thromboses in the native aorta in patients with hypoplastic left heart syndrome.  Congen Heart Dis. 2007;  2 74-78
• 15 Kawahira Y, Kishimoto H, Iio M. et al . Spontaneous aortic thrombosis in a neonate with multiple thrombi in the main branches of the abdominal aorta.  Cardiovasc Surg. 1995;  3 219-221
• 16 Kdeeg KH, Wolfel D, Rupprecht T. Diagnosis of neonatal aortic thrombosis by color coded Doppler sonography.  Pediatr Radiol. 1992;  22 62-63
• 17 Kennedy LA, Drummond WH, Knight ME. et al . Successful treatment of neonatal aortic thrombosis with tissue plasminogen activator.  Clin Lab Observ. 1990;  116 798-801
• 18 Klinger G, Hellmann J, Daneman A. Severe aortic thrombosis in the neonate-successful treatment with low-molecular-weight heparin: two case reports and review of the literature.  Am J Perinat. 2000;  17 151-158
• 19 Kohli U, Lodha R. Idiopathic neonatal aortic thrombosis.  Indian Journal of Pediatrics. 2006;  73 1127-1128
• 20 Lanari M, Lazzarotto R, Papa I. et al . Neonatal aortic arch thrombosis as a result of congenital cytomegalovirus infection.  Pediatrics. 2001;  108 E114-E117
• 21 Malin SW, Baumgart S, Rosenberg HK. et al . Nonsurgical management of obstructive aortic thrombosis complicated by renovascular hypertension in the neonate.  J Pediatr. 1985;  106 630-634
• 22 Malowany JI, Monagle P, Knoppert DC. et al . Enoxaparin for neonatal thrombosis: a call for higher dose for neonates.  Thromb Res. 2008;  122 826-830
• 23 Marcu CB, Donohue TJ, Ghantous AE. Spontaneous aortic thrombosis and embolization: antithrombin deficiency and the work-up of hypercoagulable states.  CMAJ. 2005;  173 1027-1029
• 24 Massicotte P, David M. Thrombolytic therapy in children. 2004.  (http://www.tigc.org/eguidelines/thrombolyticchild04.htm) Viewed October 2, 2009; 
• 25 Metsvaht T, Hermlin T, Kern H. et al . Aortic arch thrombosis in a neonate with heterozygous carrier status of Factor V Leiden mutation.  Congen Heart Dis. 2006;  1 40-45
• 26 Monagle P, Chalmers E, Chan AK. et al . Antithrombotic therapy in children: Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  CHEST. 2004;  126 S645-S687
• 27 Monagle P, Chan AK, deVeber G. et al . Pediatric Thromboembolism and Stroke.  3rd edition, BC Decker Inc. Hamilton, Ontario 2006; 
• 28 Monagle P, Newall F, Barnes C. et al . Arterial thromboembolic disease: a single-centre case series study.  J Pediatr Child Health. 2008;  44 28-32
• 29 Monagle P, Chalmers E, Chan AK. et al . CHEST suppl. 2008;  133 S887-S954
• 30 Morales JP, Sabharwal R, Tibby SM. et al . Successful thrombolysis of a symptomatic neonatal aortic thrombosis associated with hypernatraemic dehydration case report and literature review.  Int J Clin Pract. 2008;  62 500-507
• 31 Muñoz-Arizpe R, Walsh RF, Edge W. Obstructive aortic and renal thrombosis in the newborn – spontaneous recovery.  Pediatr Nephrol. 1992;  6 190-191
• 32 Newall F, Browne M, Savoia H. et al . Assessing the outcome of systemic tissue plasminogen activator for the management of venous and arterial thrombosis in pediatrics.  J Pediatr Hematol Oncol. 2007;  29 269-273
• 33 Newman RS, Spear GS, Kirschbaum N. Postmortem DNA diagnosis of factor V Leiden in a neonate with systemic thrombosis and probable antithrombin deficiency.  Obstet Gynecol. 1998;  92 702-705
• 34 Nowak-Gottl U, von Kries R, Gobel U. Neonatal symptomatic thromboembolism in Germany: two-year survey.  Arch Dis Child. 1997;  76 F163-F167
• 35 Olinsky A, Aitken FG, Isdale JM. Thrombus formation after umbilical arterial catheterization. An angiographic study.  S Afr Med J. 1975;  49 1467-1470
• 36 O’Neill JA, Neblett WW, Born ML. Management of major thromboembolic complications of umbilical artery catheters.  J Pediatr Surg. 1981;  16 972-997
• 37 Oppenheimer DA, Carroll BA, Garth KE. Ultrasonic detection of complications following umbilical arterial catheterization in the neonate.  Radiology. 1982;  145 667-672
• 38 Pritchard SL, Culham JAG, Rogers PCJ. Low dose fibrinolytic therapy in infants.  J Pediatr. 1985;  106 594-598
• 39 Richardson R, Applebaum H, Touran T. et al . Effective thrombolytic therapy of aortic thrombosis in the small premature infant.  J Pediatr Surg. 1988 Dec;  23 1198-1200
• 40 Rodriguez M, Sosenko I. Catheter-induced aortic thrombus masquerading as coarctation of the aorta.  Clin Pediatr (Phila). 1989 Dec;  28 581-584
• 41 Rohana J, Boo NY, Zarina A. et al . Delayed diagnosis and treatment of umbilical arterial catheter-associated aortic thrombus.  J Paediatr Child Health. 2001Oct;  37 526-527
• 42 Sahoo S, Das PK. A neonate with complete thrombosis of the aorta.  Indian J Pediatr. 2009;  76 563-564
• 43 Sanchez J, Velasco F, Alvarez R. et al . Aortic thrombosis in a neonate with hereditary antithrombin III deficiency: successful outcome with thrombolytic and replacement treatment.  Acta Paediatr. 1996;  85 245-247
• 44 Saracco P, Parodi E, Fabris C. et al . Management and investigation of neonatal thromboembolic events: genetic and acquired risk factors.  Thromb Res. 2009;  123 805-809
• 45 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry.  Pediatrics. 1995;  96 939-943
• 46 Seibert JJ, Taylor BJ, Williamson SL. et al . Sonographic detection of neonatal umbilical artery thrombosis: clinical correlation.  Am J Roent. 1987;  148 965-968
• 47 Sharathkumar AA, LaMear N, Pipe S. et al . Management of neonatal aortic arch thrombosis with low-molecular weight heparin. A case series.  J Pediatr Hem Onc. 2009;  31 516-521
• 48 Sheridan-Pereira M, Porreco RP, Hays T. et al . Neonatal aortic thrombosis associated with the lupus anticoagulant.  Obstet Gynecol. 1988;  71 1016-1018
• 49 Sherman GG, Munster M, Govendrageloo K. et al . Low molecular weight heparin in the successful treatment of a spontaneous aortic thrombosis in a neonate.  Pediatr Hematol Oncol. 2000;  17 409-413
• 50 Streif W, Ball WS, Towbin R. et al . Antithrombotic therapy in children.  Curr Opin Pediatr. 1999;  11 56-64
• 51 Strife JL, Bal WS, Towbin R. et al . Arterial occlusions in neonates: use of fibrinolytic therapy.  Radiology. 1988;  166 395-400
• 52 Torkington J, Hitchcock R, Wilkinson K. et al . Successful use of recombinant tissue plasminogen activator in the treatment of aortic thrombosis in a premature neonate.  Euro J Vasc Endovasc Surg. 1997;  13 515-516
• 53 Traivaree C, Brandao L, Chan AK. et al . Outcomes of thrombolysis for repeated courses of systemic tissue plasminogen activator for intravascular thrombosis in children.  J Thromb Haemost. 2007;  5 (S 01) P-W-413
• 54 Tuohy J, Harrison A. Prenatal transfer of anticardiolipin antibodies associated with fatal neonatal aortic thrombosis.  Aust N Z J Obstet Gynaecol. 2005;  45 175-176
• 55 Turebylu R, Salis R, Erbe R. et al . Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis.  J Perinatol. 2007;  27 490-495
• 56 Vailas GN, Brouillette RT, Scott JP. et al . Neonatal aortic thrombosis: recent experience.  J Pediatr. 1986;  109 101-108
• 57 Wang M, Hays T, Balasa V. et al . Low-dose tissue plasminogen activator thrombolysis in children.  J Pediatr Hematol Oncol. 2003;  25 379-386
• 58 Yee DL, Chan AK, Williams S. et al . Varied opinions on thrombolysis for venous thromboembolism in infants and children: findings from a survey of pediatric hematology-oncology specialists.  Pediatr Blood Cancer. 2009;  53 960-966
• 59 Zenz W, Arlt F, Sodia S. et al . Intracerebral hemorrhage during fibrinolytic therapy in children: a review of the literature of the last thirty years.  Semin Thromb Hemost. 1997;  23 321-332

Correspondence