A Avaliação e Manejo da Trombose Pós-natal M A Saxonhouse and D J Burchfield

1. 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

2. 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: saxonma@peds.ufl.edu Journal of Perinatology 2009: 29, 467–478

3. Ddos Márcio, Antenor, Leonardo e Ciro

4. 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.

5. Incidência da doença tromboembólica neonatal • 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%.

6. O sistema hemostático neonatal • 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.

7. Locais de tromboembolismo no pós-natal, exames de imagem e manejo

8. 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.

9. 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

10. 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.

11. 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.

12. 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).

13. 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.

14. 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.

15. 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.

16. Trombose venosa 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.

17. Fatores de risco para trombose pós natal

18. 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 Adquiridos Fatores de risco para o tromboembolismo

19. 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 Fatores genéticos Avaliação laboratorial para distúrbio protrombótico

20. É confuso devido limitado número de estudos Recomendado: Detalhada história familiar (desordens, história gestacional, etc) Extensiva pesquisa laboratorial de desordem protrombótica. Avaliação da trombose pós-natal clinicamente sintomática Avaliação laboratorial para distúrbio protrombótico

21. 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 antitrombótica

22. 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 recém-nascido fique resistente. • Necessita de acesso IV.

23. Terapia anticoagulante HFN X LMWH 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.

24. 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).

25. LMWH • Apesar das várias preparações todas apresentam atividade contra FXa. • Sua administração pode ser através de cateteres subcutâneos.

26. Agentes Trombolíticos • 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.

27. Terapia recomendada e doses dos agentes antitrombóticos neonatais

28. 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.

29. 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

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39. Consultem também:

40. Obrigado! Dr. Paulo R. Margotto; Ddos Márcio, Antenor, Leonardo e Ciro