A Avaliação e Manejo da
Trombose Pós-natal
M A Saxonhouse and D J Burchfield
Apresentação:Antenor Couto Neto, Márcio Teixeira
de Campos, Ciro Mendes Vargas, Leonardo Alves
Coordenação: Paulo R. Margotto
www.paulomargotto.com.br
Escola Superior de Ciências da Saúde
(ESCS)/SES/DF
8/7/2009
The evaluation and
management of postnatal
thromboses
M A Saxonhouse and D J Burchfield
Division of Neonatology, Department of
Pediatrics, University of Florida College of
Medicine, Gainesville, FL, USA
. E-mail: [email protected]
Journal of Perinatology 2009: 29, 467–478
Ddos Márcio, Antenor, Leonardo e Ciro
Estudo de Caso

Um RN a termo, masculino, nascido por parto vaginal, foi admitido
em uma UTI neonatal devido a baixos valores de APGAR e
desconforto respiratório necessitando de ventilação mecânica. A
gestação foi complicada devido à diabetes, tratado com Glyburide*,
e corioamnionite evidenciado no momento do parto. Paciente iniciou
com ampicilina e gentamicina, e reposição volêmica. Paciente
melhorou nos dias posteriores e foi capaz de ser desmamado do
ventilador. O paciente tinha um cateter umbilical arterial que foi
removido no terceiro dia de vida. No quarto dia, as pernas do
paciente tinham um aspecto pálido. Ao exame físico, os MMII
estavam frios e com marcado decréscimo de pulsos nos pés. Nas
24 horas subseqüentes, houve um decréscimo significativo de
volume urinário. O US cardíaco e de grandes vasos demonstraram
um grande trombo na Aorta descendente, com muito pouco fluxo
renal e artérias ilíacas. A procura na literatura não revelou nenhum
guideline nível I para trombose em pacientes neonatais, e a
consideração atualmente é dada para trombectomia cirúrgica,
terapia anticoagulante ou terapia fibrinolítica.
Incidência da doença
tromboembólica neonatal

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Apesar do maior risco em neonatos, a
incidência varia quanto ao tipo e quanto a
intensidade da investigação.
Todos os três registros (instituições
internacionais) mostraram acometimento em
pré-termos e a termos, em sexo masculino e
feminino, 90% estavam relacionados com
cateteres venosos centrais.
A recorrência de tromboembolismo seguindo
eventos pós-natais sintomáticos varia entre 3,3
a 7%.
O sistema hemostático neonatal

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Os sistemas pró-coagulantes, anticoagulantes e
fibrinolítico são únicos e diferentes de outras
faixas etárias.
Estão em um relativo estado pró-trombólico,
balanceados com fatores que previnem eventos
tromboembólicos em neonatos a termo e
prematuros “relativamente bem”.
Quando esse balanço é desfeito o neonato
permanece com alto risco de desenvolver
tromboses. Infecções e cateteres aumentam o
risco.
Locais de
tromboembolismo no pósnatal, exames de imagem e
manejo
Trombose arterial
Trombose arterial iatrogênica:
 A maioria das tromboses arteriais são de origem
iatrogênica, por cateteres arteriais umbilicais,
cateteres periféricos e femurais arteriais.
 Um estudo recente evidenciou tromboses
arterial em 23,4% de 47 neonatos com
cateteres umbilicais. A maioria assintomáticos,
com diagnóstico através de USG Doppler.
 As complicações incluem isquemia mesentérica,
hipertensão, disfunção renal, falha cardíaca
congestiva.
 O estudo Cochrane recomenda posicionamento
alto do cateter umbilical.
Trombose arterial
Estudos evidenciam outros fatores
responsáveis pela formação de trombos.
 Infusão continua de heparina 1,0 U/ml.
 Retirar cateter se suspeita ou confirmação
de trombose.
 Melhor método diagnostico é angiografia
contrastada.
 USG subdiagnostifica
 Tipos específicos de tratamento: heparina,
fibrinolítico e cirurgia

Trombose arterial
Trombose arterial iatrogênica:
 Condição extremamente rara, geralmente
envolve a aorta e mimetiza uma doença
cardíaca congênita.
 Atentar para redução de pulso e
extremidades frias se ECOCARDIOGRAMA
não evidenciar lesão cardíaca e coactação
da aorta.
Trombose venosa
Trombose venosa relacionada a cateter (não
cardíaco)
 Trombose venosa sintomática tem incidência de
0,24/ 10000 admissões na UTI, a maioria está
relacionada a CV.
 Mecanismos: lesão de endotélio, alteração do
fluxo, infusão de substâncias e materiais
trombogênicos.
 Cateter umbilical geralmente substituído na 1ª
semana, risco de trombose de V. porta.
Trombose venosa
Quanto menor o tempo de permanência
do cateter menor o risco de trombose.
 Padrão ouro é o venograma, porém o
mais usado é o US ( falso negativos).
 Complicações da trombose venosa:
obstrução venosa crônica, quilo tórax,
hipertensão portal e embolismo.
 Manejo requer retirada do cateter( 3-5
dias de terapia anticoagulante).

Trombose venosa
Trombose intracardíaca e trombose em
crianças com doença cardíaca congênita
 Ceteter no AD leva a dano endocárdico,
tamponamento e/ou trombo intracardíaco.
 Cateter no AD deve ser evitado (usar rt-PA)
 Trombose é uma complicação comum em
crianças que sofreram reparo de doenças
cardíacas complexas.
 Diagnóstico por ECO.
Trombose venosa
Trombose venosa renal
 Incidência de 0,5/ 1000 admissões na UTI, (mais
comum das tromboses espôntaneas)
 70% unilateral, 64% Rim E, mais comum no sexo
masculino.
 Achados: hematúria macroscópica, massa
abdominal e/ou trobocitopenia.
 Complicação aguda mais comum é a hemorragia
adrenal e extensão do coagulo para VCI.
 Monitorização, terapia anticoagulante e
fibrinolítica.
Trombose venosa
Trombose venosa portal
 Tende a ser clinicamente silenciosa
 Principais fatores de risco são cateter
venoso umbilical e sepse/onfalite.
 A resolução espontânea é relativamente
comum.
 10 anos depois pode manifestar por
hipertensão porta sem doença hepática.
Trombose venosa
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Trombose de seios venosos cerebrais
Incidência de 0.67/100.000 por ano.
30% dos casos tem infarto e hemorragia
subsequente.
Os principais achados são febre, convulsões e
letargia.
Tratamento: Anticoagulação de 6 semanas a 3
mêses. Terapia fibrinolítica e cirurgia.
Monitorização radiológica.
Fatores de risco para
trombose pós natal
Fatores Adquiridos
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A presença de
cateter venoso
central e cateteres
arteriais são os
maiores riscos
adquirido para
trombose pós-natal.
Outros fatores de
riscos: Vários fatores
coexistentes.
Fatores de risco para o tromboembolismo
Fatores genéticos
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Os estudos genéticos
enfatizam mutações que
resultam em falta ou
deficência severa de
fatores inibidores de
hemostase.
Desordens homozigóticas
protrombóticas (proteína
C, S ou antitrombina)
Desordens
heterozigóticas
protrombóticas
Avaliação laboratorial para distúrbio protrombótico
Avaliação da trombose pós-natal
clinicamente sintomática
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É confuso devido limitado
número de estudos
Recomendado:
Detalhada história
familiar (desordens,
história gestacional, etc)
Extensiva pesquisa
laboratorial de desordem
protrombótica.
Avaliação laboratorial para distúrbio protrombótico
Manejo da trombose

A complicação mais temida na terapia antitrombótica é a hemorragia
intracraniana.

Contraindicações absolutas para a terapia antitrombótica: Cirurgias do
SNC, asfixia( nos primeiros 10 dias) sangramento ativo, procedimentos
invasivos dentro de 3 dias, convulsões
Contraindicações:plaquetopenia(abaixo de 50 mil/mm3), fibrinogênio
<100mg%, INR >2, deficiência severa de coagulação, alergia ao
agente entitrombótico
Monitorização laboratorial: vide tabela
Monitorização laboratorial durante a terapia
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antitrombótica
Terapia anticoagulante
HFH (heparina ultra-fracionada) X LMWH
(heparina de baixo peso molecular)


HFN:
Meia vida curta( ajuste e descontinuação),
afetada por baixos níveis de antitrombina e
clearence de heparina faz com que o recémnascido fique resistente.
Necessita de acesso IV.
Terapia anticoagulante
HFN X LMWH

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LMWH: heparina de baixo peso molecular
Ideal para uso neonatal
Risco reduzido de hemorragia
Não necessita acesso IV
Recomenda utilizar HFN apenas a curto prazo,
especialmente se a cirurgia é indicada nas
próximas 72h.
Se anticoagulação a longo prazo é desejada,
então LMWH é a escolha mais prática na UTI.
HFN
Uso em neonatos é recomendado para
grandes tromboses fatais ou não e
clinicamente significativas, com o objetivo
prevenir expansão do coagulo ou
embolismo.
 Independentemente da dose utilizada, a
meta de tratamento é manter um anti-fator
Xa (anti-FXa) no nível de 0,3 a 0,7 U/ml
(corresponde a TTPA de 60 a 85 s).

LMWH

Apesar das várias preparações todas
apresentam atividade contra FXa.

Sua administração pode ser através de
cateteres subcutâneos.
Agentes Trombolíticos
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Trombólise deve ser considerada apenas para
tratamento trombose arterial aguda.
O trombolítico de escolha deve ser o rt-PA
Possui meia-vida curta, pouca antigenicidade e
localizada ação fibrinolítica.
Terapia recomendada e doses dos agentes antitrombóticos neonatais
Futuro
A falta de estudos clínicos randomizados.
 A aplicação retrospectiva de dados e
relatórios para pode não ser reflexo da
população que está sendo cuidadas.
 Espera-se que as complicações possam
ser minimizados e os resultados posssam
ser melhorados.
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Abstract
In the pediatric population, neonates have the highest risk for
thromboembolism (TE), most likely due to the frequent use of
intravascular catheters. This increased risk is attributed to multiple
risk factors. Randomized clinical trials dealing with management of
postnatal thromboses do not exist, thus, opinions differ regarding
optimal diagnostic and therapeutic interventions. This review begins
with an actual case study illustrating the complexity and severity of
these types of cases, and then evaluates the neonatal hemostatic
system with discussion of the common sites of postnatal thrombosis,
perinatal and prothrombotic risk factors, and potential treatment
options. A proposed step-wise evaluation of neonates with
symptomatic postnatal thromboses will be suggested, as well as
future research and registry directions. Owing to the complexity of
ischemic perinatal stroke, this topic will not be reviewed.
Keywords:
postnatal thrombosis, anticoagulation, thrombolysis,
thromboembolism
Referências (em forma de links)















Kenet G, Nowak-Gottl U. Fetal and neonatal thrombophilia. Obstet Gynecol Clin North Am 2006; 33:
457–466. | Article | PubMed |
van Ommen CH, Heijboer H, Buller HR, Hirasing RA, Heijmans HS, Peters M. Venous thromboembolism
in childhood: a prospective two-year registry in the Netherlands. J Pediatr 2001; 139: 676–
681. | Article | PubMed | ChemPort |
Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry.
Pediatrics 1995; 96: 939–943. | PubMed | ISI | ChemPort |
Nowak-Gottl U, von Kries R, Gobel U. Neonatal symptomatic thromboembolism in Germany: two year
survey. Arch Dis Child Fetal Neonatal Ed 1997; 76: F163–F167. | Article | PubMed | ChemPort |
Kurnik K, Kosch A, Strater R, Schobess R, Heller C, Nowak-Gottl U. Recurrent thromboembolism in
infants and children suffering from symptomatic neonatal arterial stroke: a prospective follow-up study.
Stroke 2003; 34: 2887–2892. | Article | PubMed |
Nowak-Gottl U, Duering C, Kempf-Bielack B, Strater R. Thromboembolic diseases in neonates and
children. Pathophysiol Haemost Thromb 2003; 33: 269–274. | Article | PubMed |
Thornburg C, Pipe S. Neonatal thromboembolic emergencies. Semin Fetal Neonatal Med 2006; 11: 198–
206. | Article | PubMed |
Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM et al. Development of the human
coagulation system in the healthy premature infant. Blood 1988; 72: 1651–1657. | PubMed | ChemPort |
Manco-Johnson MJ. Development of hemostasis in the fetus. Thromb Res 2005; 115(Suppl 1): 55–
63. | PubMed |
Ramasethu J. Management of vascular thrombosis and spasm in the newborn. Neoreviews 2005; 6:
e298–e311. | Article |
Saxonhouse M, Sola-Visner M. Current issues in the pathogenesis, diagnosis, and treatment of neonatal
thrombocytopenia. In: Ohls R, Yoder M (eds). Hematology, Immunology and Infectious Disease:
Neonatology Questions and Controversies, vol 1 Saunders Elsevier: Philadelphia, 2008, pp 11–32.
Kettner SC, Pollak A, Zimpfer M, Seybold T, Prusa AR, Herkner K et al. Heparinase-modified
thrombelastography in term and preterm neonates. Anesth Analg 2004; 98: 1650–1652, table of
contents. | Article | PubMed | ChemPort |
Andrew M, Paes B, Johnston M. Development of the hemostatic system in the neonate and young infant.
Am J Pediatr Hematol Oncol 1990; 12: 95–104. | Article | PubMed | ChemPort |
Manco-Johnson MJ. Etiopathogenesis of pediatric thrombosis. Hematology 2005; 10(Suppl 1): 167–
170. | Article | PubMed |
Journeycake JM, Manco-Johnson MJ. Thrombosis during infancy and childhood: what we know and what
we do not know. Hematol Oncol Clin North Am 2004; 18: 1315–1338, viii–ix. | Article | PubMed |















Manco-Johnson MJ. Controversies in neonatal thrombotic disorders. In: Ohls R, MC Y (eds).
Hematology, Immunology, and Infectious Disease: Neonatology Questions and Controversies, vol
1 Saunders Elsevier: Philadelphia, 2008, pp 58–74.
Turebylu R, Salis R, Erbe R, Martin D, Lakshminrusimha S, Ryan RM. Genetic prothrombotic
mutations are common in neonates but are not associated with umbilical catheter-associated
thrombosis. J Perinatol 2007; 27: 490–495. | Article | PubMed | ChemPort |
Greenway A, Massicotte MP, Monagle P. Neonatal thrombosis and its treatment. Blood Rev 2004;
18: 75–84. | Article | PubMed | ChemPort |
Vailas GN, Brouillette RT, Scott JP, Shkolnik A, Conway J, Wiringa K. Neonatal aortic thrombosis:
recent experience. J Pediatr 1986; 109: 101–108. | Article | PubMed | ChemPort |
Tanke RB, van Megen R, Daniels O. Thrombus detection on central venous catheters in the
neonatal intensive care unit. Angiology 1994; 45: 477–480. | Article | PubMed | ChemPort |
Schmidt B, Zipursky A. Thrombotic disease in newborn infants. Clin Perinatol 1984; 11: 461–
488. | PubMed | ChemPort |
Lau KK, Stoffman JM, Williams S, McCusker P, Brandao L, Patel S et al. Neonatal renal vein
thrombosis: review of the English-language literature between 1992 and 2006. Pediatrics 2007;
120: e1278–e1284. | Article | PubMed |
Kosch A, Kuwertz-Broking E, Heller C, Kurnik K, Schobess R, Nowak-Gottl U. Renal venous
thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood 2004; 104:
1356–1360. | Article | PubMed | ISI | ChemPort |
Marks SD, Massicotte MP, Steele BT, Matsell DG, Filler G, Shah PS et al. Neonatal renal venous
thrombosis: clinical outcomes and prevalence of prothrombotic disorders. J Pediatr 2005; 146:
811–816. | Article | PubMed |
deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ et al. Cerebral sinovenous
thrombosis in children. N Engl J Med 2001; 345: 417–423. | Article | PubMed | ISI | ChemPort |
Wasay M, Dai AI, Ansari M, Shaikh Z, Roach ES. Cerebral venous sinus thrombosis in children: a
multicenter cohort from the United States. J Child Neurol 2008; 23: 26–31. | Article | PubMed |
Shroff M, deVeber G. Sinovenous thrombosis in children. Neuroimaging Clin N Am 2003; 13:
115–138. | Article | PubMed |
de Veber G, Adams M, Andrew M. Cerebral thromboembolism in neonates: clinical and
radiographic features. Blood 1998; 92: 2959. | PubMed |
Beardsley DS. Venous thromboembolism in the neonatal period. Semin Perinatol 2007; 31: 250–
253. | Article | PubMed |
Rosendaal FR. Venous thrombosis: the role of genes, environment, and behavior. Hematology
(Am Soc Hematol Educ Program) 2005; 1–12.















Seligsohn U, Zivelin A. Thrombophilia as a multigenic disorder. Thromb Haemost 1997; 78: 297–
301. | PubMed | ChemPort |
Nowak-Gottl U, Junker R, Kreuz W, von Eckardstein A, Kosch A, Nohe N et al. Risk of recurrent venous
thrombosis in children with combined prothrombotic risk factors. Blood 2001; 97: 858–
862. | Article | PubMed | ChemPort |
Nowak-Gottl U, Strater R, Heinecke A, Junker R, Koch HG, Schuierer G et al. Lipoprotein (a) and genetic
polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of
spontaneous ischemic stroke in childhood. Blood 1999; 94: 3678–3682. | PubMed | ChemPort |
Nowak-Gottl U, Junker R, Hartmeier M, Koch HG, Munchow N, Assmann G et al. Increased lipoprotein(a) is an
important risk factor for venous thromboembolism in childhood. Circulation 1999; 100: 743–
748. | PubMed | ChemPort |
Bucciarelli P, Rosendaal FR, Tripodi A, Mannucci PM, De Stefano V, Palareti G et al. Risk of venous
thromboembolism and clinical manifestations in carriers of antithrombin, protein C, protein S deficiency, or
activated protein C resistance: a multicenter collaborative family study. Arterioscler Thromb Vasc Biol 1999; 19:
1026–1033. | PubMed | ChemPort |
Brenner B. Thrombophilia and adverse pregnancy outcome. Obstet Gynecol Clin North Am 2006; 33: 443–456,
ix. | Article | PubMed |
Boffa MC, Lachassinne E. Infant perinatal thrombosis and antiphospholipid antibodies: a review. Lupus 2007; 16:
634–641. | Article | PubMed |
Manco-Johnson MJ, Grabowski EF, Hellgreen M, Kemahli AS, Massicotte MP, Muntean W et al. Laboratory
testing for thrombophilia in pediatric patients. On behalf of the Subcommittee for Perinatal and Pediatric
Thrombosis of the Scientific and Standardization Committee of the International Society of Thrombosis and
Haemostasis (ISTH). Thromb Haemost 2002; 88: 155–156. | PubMed | ChemPort |
Male C, Johnston M, Sparling C, Brooker L, Andrew M, Massicotte P. The influence of developmental
haemostasis on the laboratory diagnosis and management of haemostatic disorders during infancy and childhood.
Clin Lab Med 1999; 19: 39–69. | PubMed | ChemPort |
Wu YW, Lynch JK, Nelson KB. Perinatal arterial stroke: understanding mechanisms and outcomes. Semin Neurol
2005; 25: 424–434. | Article | PubMed |
Raju TN, Nelson KB, Ferriero D, Lynch JK. Ischemic perinatal stroke: summary of a workshop sponsored by the
National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and
Stroke. Pediatrics 2007; 120: 609–616. | Article | PubMed |
Martinelli I, Taioli E, Cetin I, Marinoni A, Gerosa S, Villa MV et al. Mutations in coagulation factors in women with
unexplained late fetal loss. N Engl J Med 2000; 343: 1015–1018. | Article | PubMed | ChemPort |
Manco-Johnson MJ, Abshire TC, Jacobson LJ, Marlar RA. Severe neonatal protein C deficiency: prevalence and
thrombotic risk. J Pediatr 1991; 119: 793–798. | Article | PubMed | ChemPort |
Lynch JK, Nelson KB. Epidemiology of perinatal stroke. Curr Opin Pediatr 2001; 13: 499–
505. | Article | PubMed | ChemPort |
Leistra-Leistra MJ, Timmer A, van Spronsen FJ, Geven WB, van der Meer J, Erwich JJ. Fetal thrombotic
vasculopathy in the placenta: a thrombophilic connection between pregnancy complications and neonatal
thrombosis? Placenta 2004; 25(Suppl A): S102–S105. | Article | PubMed | ChemPort |















Lee J, Croen LA, Backstrand KH, Yoshida CK, Henning LH, Lindan C et al. Maternal and infant
characteristics associated with perinatal arterial stroke in the infant. JAMA 2005; 293: 723–
729. | Article | PubMed | ChemPort |
Laugesaar R, Kolk A, Tomberg T, Metsvaht T, Lintrop M, Varendi H et al. Acutely and retrospectively
diagnosed perinatal stroke: a population-based study. Stroke 2007; 38: 2234–2240. | Article | PubMed |
Grandone E, Margaglione M, Colaizzo D, D'Andrea G, Cappucci G, Brancaccio V et al. Genetic
susceptibility to pregnancy-related venous thromboembolism: roles of factor V Leiden, prothrombin
G20210A, and methylenetetrahydrofolate reductase C677T mutations. Am J Obstet Gynecol 1998; 179:
1324–1328. | Article | PubMed | ChemPort |
den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH et al. Hyperhomocysteinemia as a risk
factor for deep-vein thrombosis. N Engl J Med 1996; 334: 759–762. | Article | PubMed | ChemPort |
de Veber G. Canadian pediatric iscaemic stroke registry. Pediatr Child Health 2000b; A17.
Saxonhouse M, Manco-Johnson M. The evaluation and management of neonatal coagulation disorders.
Semin Perinatol 2009; 33: 52–65. | Article | PubMed |
Ramasethu J. Complications of vascular catheters in the neonatal intensive care unit. Clin Perinatol
2008; 35: 199–222, x. | Article | PubMed |
Fletcher MA, Brown DR, Landers S, Seguin J. Umbilical arterial catheter use: report of an audit
conducted by the Study Group for Complications of Perinatal Care. Am J Perinatol 1994; 11: 94–
99. | Article | PubMed | ISI | ChemPort |
Seibert JJ, Northington FJ, Miers JF, Taylor BJ. Aortic thrombosis after umbilical artery catheterization in
neonates: prevalence of complications on long-term follow-up. AJR Am J Roentgenol 1991; 156: 567–
569. | PubMed | ChemPort |
Nouri S, Mahdhaoui N, Beizig S, Salem N, Methlouthi J, Ben Dhafer S et al. [Major neonatal aortic
thrombosis: a case report]. Arch Pediatr 2007; 14: 1097–1100. | Article | PubMed | ChemPort |
Joshi VV, Draper DA, Bates III RD. Neonatal necrotizing enterocolitis. Occurrence secondary to
thrombosis of abdominal aorta following umbilical arterial catheterization. Arch Pathol 1975; 99: 540–
543. | PubMed | ISI | ChemPort |
Greenberg R, Waldman D, Brooks C, Ouriel K, Pegoli W, Ryan R et al. Endovascular treatment of renal
artery thrombosis caused by umbilical artery catheterization. J Vasc Surg 1998; 28: 949–
953. | Article | PubMed | ISI | ChemPort |
Barrington KJ. Umbilical artery catheters in the newborn: effects of position of the catheter tip. Cochrane
Database Syst Rev 2000 CD000505.
Barrington K. Umbilical artery catheters in the newborn: effects of position of the catheter tip. Cochrane
Database Sys Rev 1999.
Barrington KJ. Umbilical artery catheters in the newborn: effects of heparin. Cochrane Database Syst
Rev 2000 CD000507.















Kenny D, Tsai-Goodman B. Neonatal arterial thrombus mimicking congenital heart disease. Arch Dis Child Fetal
Neonatal Ed 2007; 92: F59–F61. | Article | PubMed | ChemPort |
Alioglu B, Ozyurek E, Tarcan A, Atac FB, Gurakan B, Ozbek N. Heterozygous methylenetetrahydrofolate
reductase 677C-T gene mutation with mild hyperhomocysteinemia associated with intrauterine iliofemoral artery
thrombosis. Blood Coagul Fibrinolysis 2006; 17: 495–498. | Article | PubMed | ChemPort |
Chidi CC, King DR, Boles Jr ET. An ultrastructural study of the intimal injury induced by an indwelling umbilical
artery catheter. J Pediatr Surg 1983; 18: 109–115. | Article | PubMed | ChemPort |
Wakefield A, Cohen Z, Rosenthal A, Craig M, Jeejeebhoy KN, Gotlieb A et al. Thrombogenicity of total parenteral
nutrition solutions: II. Effect on induction of endothelial cell procoagulant activity. Gastroenterology 1989; 97:
1220–1228. | PubMed | ChemPort |
Pottecher T, Forrler M, Picardat P, Krause D, Bellocq JP, Otteni JC. Thrombogenicity of central venous catheters:
prospective study of polyethylene, silicone and polyurethane catheters with phlebography or post-mortem
examination. Eur J Anaesthesiol 1984; 1: 361–365. | PubMed | ChemPort |
Khilnani P, Goldstein B, Todres ID. Double lumen umbilical venous catheters in critically ill neonates: a
randomized prospective study. Crit Care Med 1991; 19: 1348–1351. | Article | PubMed | ChemPort |
Junker P, Egeblad M, Nielsen O, Kamper J. Umbilical vein catheterization and portal hypertension. Acta Paediatr
Scand 1976; 65: 499–504. | Article | PubMed | ChemPort |
O'Grady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG et al. Guidelines for the prevention of
intravascular catheter-related infections. The Hospital Infection Control Practices Advisory Committee, Center for
Disease Control and Prevention, US. Pediatrics 2002; 110: e51. | Article | PubMed |
Butler-O'Hara M, Buzzard CJ, Reubens L, McDermott MP, DiGrazio W, D'Angio CT. A randomized trial comparing
long-term and short-term use of umbilical venous catheters in premature infants with birth weights of less than
1251 grams. Pediatrics 2006; 118: e25–e35. | Article | PubMed | ISI |
Albisetti M, Andrew M, Monagle P. Hemostatic abnormalities. In: de Alarcon P, Werner E (eds). Neonatal
Hematology. Cambridge University Press: United Kingdom, 2005, pp 310–348.
Le Coultre C, Oberhansli I, Mossaz A, Bugmann P, Faidutti B, Belli DC. Postoperative chylothorax in children:
differences between vascular and traumatic origin. J Pediatr Surg 1991; 26: 519–
523. | Article | PubMed | ChemPort |
Barnes C, Newall F, Monagle P. Post-thrombotic syndrome. Arch Dis Child 2002; 86: 212–
214. | Article | PubMed | ChemPort |
Monagle P, Chalmers E, Chan A, DeVeber G, Kirkham F, Massicotte P et al. Antithrombotic therapy in neonates
and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition).
Chest 2008; 133: 887S–968S. | Article | PubMed | ChemPort |
Darling JC, Newell SJ, Dear PR. Placement of neonatal central venous catheter tips in the right atrium: a practice
to be avoided? Arch Dis Child Fetal Neonatal Ed 2001; 85: F146. | Article | PubMed | ChemPort |
Cartwright DW. Central venous lines in neonates: a study of 2186 catheters. Arch Dis Child Fetal Neonatal Ed
2004; 89: F504–F508. | Article | PubMed | ChemPort |















Marks KA, Zucker N, Kapelushnik J, Karplus M, Levitas A. Infective endocarditis successfully treated in extremely
low birth weight infants with recombinant tissue plasminogen activator. Pediatrics 2002; 109: 153–
158. | Article | PubMed |
Darling JC, Newell SJ, Mohamdee O, Uzun O, Cullinane CJ, Dear PR. Central venous catheter tip in the right
atrium: a risk factor for neonatal cardiac tamponade. J Perinatol 2001; 21: 461–
464. | Article | PubMed | ChemPort |
Torres-Valdivieso MJ, Cobas J, Barrio C, Munoz C, Pascual M, Orbea C et al. Successful use of tissue
plasminogen activator in catheter-related intracardiac thrombus of a premature infant. Am J Perinatol 2003; 20:
91–96. | Article | PubMed | ChemPort |
Wang M, Hays T, Balasa V, Bagatell R, Gruppo R, Grabowski EF et al. Low-dose tissue plasminogen activator
thrombolysis in children. J Pediatr Hematol Oncol 2003; 25: 379–386. | Article | PubMed |
Tardin FA, Avanza Jr AC, Andiao MR, Rabello SM, Cristello Ede M, Baltan EC et al. Combined rTPA and aspirin
therapy for intracardiac thrombosis in neonates. Arq Bras Cardiol 2007; 88: e121–e123. | Article | PubMed |
Rimensberger PC, Humbert JR, Beghetti M. Management of preterm infants with intracardiac thrombi: use of
thrombolytic agents. Paediatr Drugs 2001; 3: 883–898. | Article | PubMed | ChemPort |
Cholette JM, Rubenstein JS, Alfieris GM, McDermott MP, Harmon WG, Vermilion R et al. Elevated risk of
thrombosis in neonates undergoing initial palliative cardiac surgery. Ann Thorac Surg 2007; 84: 1320–
1325. | Article | PubMed |
Fenton KN, Siewers RD, Rebovich B, Pigula FA. Interim mortality in infants with systemic-to-pulmonary artery
shunts. Ann Thorac Surg 2003; 76: 152–156; discussion 156–157. | Article | PubMed |
Messinger Y, Sheaffer JW, Mrozek J, Smith CM, Sinaiko AR. Renal outcome of neonatal renal venous thrombosis:
review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients. Pediatrics 2006; 118: e1478–
e1484. | Article | PubMed |
Kim JH, Lee YS, Kim SH, Lee SK, Lim MK, Kim HS. Does umbilical vein catheterization lead to portal venous
thrombosis? Prospective US evaluation in 100 neonates. Radiology 2001; 219: 645–
650. | PubMed | ISI | ChemPort |
Chalmers EA. Perinatal stroke—risk factors and management. Br J Haematol 2005; 130: 333–
343. | Article | PubMed | ISI |
Wu YW, Hamrick SE, Miller SP, Haward MF, Lai MC, Callen PW et al. Intraventricular hemorrhage in term
neonates caused by sinovenous thrombosis. Ann Neurol 2003; 54: 123–126. | Article | PubMed |
Manco-Johnson MJ. How I treat venous thrombosis in children. Blood 2006; 107: 21–
29. | Article | PubMed | ChemPort |
deVeber GA, MacGregor D, Curtis R, Mayank S. Neurologic outcome in survivors of childhood arterial ischemic
stroke and sinovenous thrombosis. J Child Neurol 2000; 15: 316–324. | Article | PubMed | ChemPort |
Golomb MR, deVeber GA, MacGregor DL, Domi T, Whyte H, Stephens D et al. Independent walking after
neonatal arterial ischemic stroke and sinovenous thrombosis. J Child Neurol 2003; 18: 530–
536. | Article | PubMed |










Wong VK, LeMesurier J, Franceschini R, Heikali M, Hanson R. Cerebral venous
thrombosis as a cause of neonatal seizures. Pediatr Neurol 1987; 3: 235–
237. | Article | PubMed | ChemPort |
Barrington KJ. Umbilical artery catheters in the newborn: effects of catheter design
(end vs side hole). Cochrane Database Syst Rev 2000 CD000508.
Barrington KJ. Umbilical artery catheters in the newborn: effects of catheter materials.
Cochrane Database Syst Rev 2000 CD000949.
Boros SJ, Thompson TR, Reynolds JW, Jarvis CW, Williams HJ. Reduced thrombus
formation with silicone elastomere (silastic) umbilical artery catheters. Pediatrics
1975; 56: 981–986. | PubMed | ChemPort |
Andrews EJ, Hughes Jr HC. Thromboembolic sequelae to indwelling silastic cannulas
in sheep arteries. J Biomed Mater Res 1973; 7: 137–
144. | Article | PubMed | ChemPort |
Gursel T, Kocak U, Kaya Z, Bukulmez A, Atalay Y. Activated protein C resistance in
cord blood from healthy and complicated newborns. J Matern Fetal Neonatal Med
2007; 20: 797–801. | Article | PubMed | ChemPort |
Khan JU, Takemoto CM, Casella JF, Streiff MB, Nwankwo IJ, Kim HS. Catheterdirected thrombolysis of inferior vena cava thrombosis in a 13-day-old neonate and
review of literature. Cardiovasc Intervent Radiol 2008; 31: S153–
S160. | Article | PubMed |
Formstone CJ, Hallam PJ, Tuddenham EG, Voke J, Layton M, Nicolaides K et al.
Severe perinatal thrombosis in double and triple heterozygous offspring of a family
segregating two independent protein S mutations and a protein C mutation. Blood
1996; 87: 3731–3737. | PubMed | ChemPort |
Zoller B, Hillarp A, Berntorp E, Dahlback B. Activated protein C resistance due to a
common factor V gene mutation is a major risk factor for venous thrombosis. Annu
Rev Med 1997; 48: 45–58. | Article | PubMed | ChemPort |
Nowak-Gottl U, Dubbers A, Kececioglu D, Koch HG, Kotthoff S, Runde J et al. Factor
V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a
prospective study. J Pediatr 1997; 131: 608–612. | Article | PubMed | ChemPort |















Fijnheer R, Paijmans B, Verdonck LF, Nieuwenhuis HK, Roest M, Dekker AW. Factor V Leiden in central venous
catheter-associated thrombosis. Br J Haematol 2002; 118: 267–270. | Article | PubMed | ISI | ChemPort |
Lammle B, Kremer Hovinga JA, Alberio L. Thrombotic thrombocytopenic purpura. J Thromb Haemost 2005; 3:
1663–1675. | Article | PubMed | ChemPort |
Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women.
Implications for venous thromboembolism screening. JAMA 1997; 277: 1305–
1307. | Article | PubMed | ISI | ChemPort |
Zoller B, Norlund L, Leksell H, Nilsson JE, von Schenck H, Rosen U et al. High prevalence of the FVR506Q
mutation causing APC resistance in a region of southern Sweden with a high incidence of venous thrombosis.
Thromb Res 1996; 83: 475–477. | Article | PubMed | ChemPort |
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of
the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous
thrombosis. Blood 1996; 88: 3698–3703. | PubMed | ISI | ChemPort |
Junker R, Koch HG, Auberger K, Munchow N, Ehrenforth S, Nowak-Gottl U. Prothrombin G20210A gene mutation
and further prothrombotic risk factors in childhood thrombophilia. Arterioscler Thromb Vasc Biol 1999; 19: 2568–
2572. | PubMed | ISI | ChemPort |
Keku T, Millikan R, Worley K, Winkel S, Eaton A, Biscocho L et al. 5,10-Methylenetetrahydrofolate reductase
codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites. Cancer Epidemiol
Biomarkers Prev 2002; 11: 1611–1621. | PubMed | ISI | ChemPort |
Rady PL, Szucs S, Grady J, Hudnall SD, Kellner LH, Nitowsky H et al. Genetic polymorphisms of
methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) in ethnic populations
in Texas; a report of a novel MTHFR polymorphic site, G1793A. Am J Med Genet 2002; 107: 162–
168. | Article | PubMed |
Schneppenheim R, Greiner J. Thrombosis in infants and children. Hematology (Am Soc Hematol Educ Program)
2006; 86–96.
Eldibany MM, Caprini JA. Hyperhomocysteinemia and thrombosis: an overview. Arch Pathol Lab Med 2007; 131:
872–884. | PubMed | ChemPort |
Rook JL, Nugent DJ, Young G. Pediatric stroke and methylenetetrahydrofolate reductase polymorphisms: an
examination of C677T and A1298C mutations. J Pediatr Hematol Oncol 2005; 27: 590–593. | Article | PubMed |
van Hylckama Vlieg A, van der Linden IK, Bertina RM, Rosendaal FR. High levels of factor IX increase the risk of
venous thrombosis. Blood 2000; 95: 3678–3682. | PubMed | ChemPort |
Meijers JC, Tekelenburg WL, Bouma BN, Bertina RM, Rosendaal FR. High levels of coagulation factor XI as a risk
factor for venous thrombosis. N Engl J Med 2000; 342: 696–701. | Article | PubMed | ChemPort |
Nelson KB. Perinatal ischemic stroke. Stroke 2007; 38: 742–745. | Article | PubMed |
Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R et al. Heparin and low-molecularweight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001;
119: 64S–94S. | Article | PubMed | ISI | ChemPort |

















Frost J, Mureebe L, Russo P, Russo J, Tobias JD. Heparin-induced thrombocytopenia in the pediatric
intensive care unit population. Pediatr Crit Care Med 2005; 6: 216–219. | Article | PubMed |
Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic therapy in children: the
Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126: 645S–
687S. | Article | PubMed | ChemPort |
Andrew M, Marzinotto V, Massicotte P, Blanchette V, Ginsberg J, Brill-Edwards P et al. Heparin therapy
in pediatric patients: a prospective cohort study. Pediatr Res 1994; 35: 78–
83. | Article | PubMed | ChemPort |
Young TE, Mangum B. NEOFAX 2008, 21st edn, vol 1 Thomson Reuters: Montvale, 2008, 358pp.
Spadone D. Heparin induced thrombocytopenia in the newborn. J Vasc Surg 1996; 15: 306–312.
Martchenke J, Boshkov L. Heparin-induced thrombocytopenia in neonates. Neonatal Netw 2005; 24: 33–
37. | PubMed |
Streif W, Goebel G, Chan AK, Massicotte MP. Use of low molecular mass heparin (enoxaparin) in
newborn infants: a prospective cohort study of 62 patients. Arch Dis Child Fetal Neonatal Ed 2003; 88:
F365–F370. | Article | PubMed | ChemPort |
Michaels LA, Gurian M, Hegyi T, Drachtman RA. Low molecular weight heparin in the treatment of
venous and arterial thromboses in the premature infant. Pediatrics 2004; 114: 703–
707. | Article | PubMed | ISI |
Massicotte P, Adams M, Marzinotto V, Brooker LA, Andrew M. Low-molecular-weight heparin in pediatric
patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128: 313–
318. | Article | PubMed | ISI | ChemPort |
Malowany JI, Knoppert DC, Chan AK, Pepelassis D, Lee DS. Enoxaparin use in the neonatal intensive
care unit: experience over 8 years. Pharmacotherapy 2007; 27: 1263–
1271. | Article | PubMed | ChemPort |
Malowany JI, Monagle P, Knoppert DC, Lee DS, Wu J, McCusker P et al. Enoxaparin for neonatal
thrombosis: a call for a higher dose for neonates. Thromb Res 2008; 122(6): 826–
830. | Article | PubMed | ChemPort |
Edstrom CS, McBride J, Theriaque D, Kao KJ, Christensen RD. Obtaining blood samples for anti-factor
Xa quantification through umbilical artery catheters. J Perinatol 2002; 22: 475–477. | Article | PubMed |
Williams MD, Chalmers EA, Gibson BE. The investigation and management of neonatal haemostasis
and thrombosis. Br J Haematol 2002; 119: 295–309. | Article | PubMed |
Nowak-Gottl U, Auberger K, Halimeh S, Junker R, Klinge J, Kreuz WD et al. Thrombolysis in newborns
and infants. Thromb Haemost 1999; 82(Suppl 1): 112–116. | PubMed |
Andrew M, DeVeber G. Pediatric Thromboembolism and Stroke Protocols. BC Decker Inc., Hamilton:
Canada, 1997.
Coombs CJ, Richardson PW, Dowling GJ, Johnstone BR, Monagle P. Brachial artery thrombosis in
infants: an algorithm for limb salvage. Plast Reconstr Surg 2006; 117: 1481–
1488. | Article | PubMed | ChemPort |
Weitz JI, Hirsh J. New anticoagulant drugs. Chest 2001; 119: 95S–107S. | Article | PubMed | ChemPort |
Consultem também:
Hemorragia intraventricular no
recém-nascido a termo
Autor(es): Paulo R. Margotto
Hemorragia intraventricular e
talâmica em um recém-nascido
a termo com aumento de
anticorpos antifosfolípides
Autor(es): Paulo R. Margotto
Obrigado!
Dr. Paulo R. Margotto; Ddos Márcio, Antenor, Leonardo e Ciro