The emerging role of immunothrombosis in paediatric conditions

Franchi, Thomas; Eaton, Simon; Coppi, Paolo De; Giuliani, Stefano

doi:10.1038/s41390-019-0343-6

Cited by 14 publications

(11 citation statements)

References 96 publications

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“…Moreover, exacerbations of cardiovascular disease, including acute myocardial infarction and unstable angina, have been observed in bacteraemic infections caused by Neisseria meningitidis and Staphylococcus aureus (14–16). This association is not limited to adults but is also observed in children in acute conditions such as sepsis, necrotizing enterocolitis, and otitis media; or in chronic pulmonary infections caused by respiratory syncytial virus or Pseudomonas aeruginosa (17). Since thrombosis is observed after infection with a diverse range of pathogens, it suggests the ultimate risk of thrombosis after infection is influenced by both host and pathogen-derived factors (15).…”

Section: Introductionmentioning

confidence: 98%

Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models

Beristain‐Covarrubias

et al. 2019

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Thrombosis is a common consequence of infection that is associated with poor patient outcome. Nevertheless, the mechanisms by which infection-associated thrombosis is induced, maintained and resolved are poorly understood, as is the contribution thrombosis makes to host control of infection and pathogen spread. The key difference between infection-associated thrombosis and thrombosis in other circumstances is a stronger inflammation-mediated component caused by the presence of the pathogen and its products. This inflammation triggers the activation of platelets, which may accompany damage to the endothelium, resulting in fibrin deposition and thrombus formation. This process is often referred to as thrombo-inflammation. Strikingly, despite its clinical importance and despite thrombi being induced to many different pathogens, it is still unclear whether the mechanisms underlying this process are conserved and how we can best understand this process. This review summarizes thrombosis in a variety of models, including single antigen models such as LPS, and infection models using viruses and bacteria. We provide a specific focus on Salmonella Typhimurium infection as a useful model to address all stages of thrombosis during infection. We highlight how this model has helped us identify how thrombosis can appear in different organs at different times and thrombi be detected for weeks after infection in one site, yet largely be resolved within 24 h in another. Furthermore, we discuss the observation that thrombi induced to Salmonella Typhimurium are largely devoid of bacteria. Finally, we discuss the value of different therapeutic approaches to target thrombosis, the potential importance of timing in their administration and the necessity to maintain normal hemostasis after treatment. Improvements in our understanding of these processes can be used to better target infection-mediated mechanisms of thrombosis.

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Section: Introductionmentioning

confidence: 98%

Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models

Beristain‐Covarrubias

et al. 2019

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“…As noted, endothelial cells are critical in modulating the balance between activation of coagulation and fibrinolysis mediated through the binding of thrombin to thrombomodulin ( Figure 3B). Additionally, platelet-neutrophil interactions are important in the formation of Neutrophil Extracellular Traps (NETs) and the process of NETosis which can induce a process referred to as immunothrombosis (Figure 4) (44,45).…”

Section: Hemostasis and The Regulation Of Clot Formationmentioning

confidence: 99%

“…Study details of the Andrew et al series describing the developing hemostatic system during infancy, childhood, and adolescence(45)(46)(47). Normal values from birth to 6 months old in the healthy term infant and preterm infant, and from 1 to 16 years old in the child and FXI, FXII, HWMK, and PK were lower in term and preterm infants in the postnatal period compared to adults• FXI and FXII decreased at 11 to 16 years old compared to adults• FV decreased throughout childhood and was lowest in adolescence• FVIII and vWf were similar in term and preterm infants and reached near or above adult values by 6 months…”

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Hemostatic Testing in Critically Ill Infants and Children

Nair

Parker

2021

Front. Pediatr.

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Children with critical illness frequently manifest imbalances in hemostasis with risk of consequent bleeding or pathologic thrombosis. Traditionally, plasma-based tests measuring clot formation by time to fibrin clot generation have been the “gold standard” in hemostasis testing. However, these tests are not sensitive to abnormalities in fibrinolysis or in conditions of enhanced clot formation that may lead to thrombosis. Additionally, they do not measure the critical roles played by platelets and endothelial cells. An added factor in the evaluation of these plasma-based tests is that in infants and young children plasma levels of many procoagulant and anticoagulant proteins are lower than in older children and adults resulting in prolonged clot generation times in spite of maintaining a normal hemostatic “balance.” Consequently, newer assays directly measuring thrombin generation in plasma and others assessing the stages hemostasis including clot initiation, propagation, and fibrinolysis in whole blood by viscoelastic methods are now available and may allow for a global measurement of the hemostatic system. In this manuscript, we will review the processes by which clots are formed and by which hemostasis is regulated, and the rationale and limitations for the more commonly utilized tests. We will also discuss selected newer tests available for the assessment of hemostasis, their “pros” and “cons,” and how they compare to the traditional tests of coagulation in the assessment and management of critically ill children.

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“…27 Os níveis mais altos de d-dímero nos pacientes com dilatação de artéria coronária em nosso estudo destacam uma importante via fisiopatológica que necessita ser mais investigada em pacientes com SIM-P. Com base no papel crescente da imunotrombose nas doenças pediátricas, tais como sepse e doenças reumáticas autoimunes, pode-se levantar a hipótese de que bloquear a cascata de coagulação pode contribuir para diminuir a resposta inflamatória. 28 De fato, várias publicações descreveram as propriedades não anticoagulantes da heparina, tais como inibindo a quimiotaxia de neutrófilos e a migração de leucócitos, neutralizando o fator de complemento C5a carregado positivamente, e sequestrando proteínas de fase aguda, com consequente diminuição de biomarcadores inflamatórios. 29 Portanto, a heparina também atuaria como terapia anti-inflamatória adjuvante em pacientes com SIM-P e inflamação da artéria coronária, juntamente com imunoglobulina endovenosa, corticosteroides e agentes imunobiológicos.…”

Section: Artigo Originalunclassified

O Coração de Pacientes Pediátricos com COVID-19: Novos Insights a Partir de um Estudo Ecocardiográfico Sistemático em um Hospital Terciário no Brasil

Diniz¹,

Cardoso²,

Sawamura³

et al. 2021

Arquivos Brasileiros De Cardiologia

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Fundamento: A pandemia da COVID-19 representa uma enorme carga para o sistema de saúde do mundo. Apesar de pacientes pediátricos terem sido relativamente poupados em comparação a adultos, estudos recentes mostraram um número crescente de pacientes críticos com Síndrome Inflamatória Multisistêmica Pediátrica (SIM-P) com disfunção cardiovascular importante. No entanto, pouco se conhece a respeito da relação entre anormalidades cardíacas e biomarcadores inflamatórios e de coagulação. Objetivos: Investigar anormalidades ecocardiográficas em pacientes pediátricos com COVID-19 admitidos em um hospital terciário. Métodos: Este foi um estudo longitudinal retrospectivo, baseado na revisão de prontuários médicos e ecocardiogramas de pacientes (0-19 anos) admitidos em um hospital terciário entre 30 de março e 30 de junho de 2020. Para a análise estatística, o nível de significância foi estabelecido em 5% (p<0,05). Resultados: Foram incluídos 48 pacientes, 73% com doenças pré-existentes, 20 (41,7%) com SIM-P. A idade mediana foi 7,5 (0-18,6) anos; 27 (56,2%) eram do sexo masculino. A duração mediana de internação foi 15,4 (2-92) dias e sete (14,6%) pacientes morreram. Um total de 70 ecocardiografias foram realizadas, 66,7% submeteram-se ao exame somente uma vez, e 33,3% várias vezes. Vinte e três (48%) pacientes apresentaram anormalidades no ecocardiograma: oito (16.6%) disfunção sistólica do ventrículo esquerdo, seis (12.5%) disfunção sistólica do ventrículo direito, e 12 (25%) dilatação da artéria coronária (Z-score>+2,5). Anormalidades ecocardiográficas foram significativamente associadas com SIM-P, admissão na unidade de terapia intensiva pediátrica, suporte ventilatório/vasoativo, e morte (p<0,05). Níveis significativamente mais altos de d-dímero (ng/mL) foram detectados em pacientes com disfunção ventricular esquerda [16733(4157-115668) vs. 2406.5(190-95040)], disfunção ventricular direita [25769(3422-115668) vs. 2803.5(190-95040)] e dilatação da artéria coronária [9652.5(921-115668) vs. 2724(190-95040)] (p<0,05). Conclusão: Anormalidades ecocardiográficas eram frequentes nos pacientes pediátricos com COVID-19 e associadas com piores desfechos clínicos. Exacerbação das vias de inflamação e coagulação pode exercer um importante papel na lesão cardiovascular nesses pacientes.

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The emerging role of immunothrombosis in paediatric conditions

Cited by 14 publications

References 96 publications

Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models

Understanding Infection-Induced Thrombosis: Lessons Learned From Animal Models

Hemostatic Testing in Critically Ill Infants and Children

O Coração de Pacientes Pediátricos com COVID-19: Novos Insights a Partir de um Estudo Ecocardiográfico Sistemático em um Hospital Terciário no Brasil

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