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Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)

Introduction: Paediatric Inflammatory Multisystem Syndrome - temporally associated with SARS-CoV2 (PIMS-TS) is a newly described syndrome during the COVID-19 pandemic. It is characterised by a state of persistent fever, inflammation and organ dysfunction following exposure to SARS-CoV-2 virus. It sh...

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Autores principales: Lam, Ho Pui Jeff, Alamelu, Jayanthi, Brighouse, James, Miller, Owen, Lillie, Jonathan, Inusa, Baba PD
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330267/
http://dx.doi.org/10.1182/blood-2020-142424
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author Lam, Ho Pui Jeff
Alamelu, Jayanthi
Brighouse, James
Miller, Owen
Lillie, Jonathan
Inusa, Baba PD
author_facet Lam, Ho Pui Jeff
Alamelu, Jayanthi
Brighouse, James
Miller, Owen
Lillie, Jonathan
Inusa, Baba PD
author_sort Lam, Ho Pui Jeff
collection PubMed
description Introduction: Paediatric Inflammatory Multisystem Syndrome - temporally associated with SARS-CoV2 (PIMS-TS) is a newly described syndrome during the COVID-19 pandemic. It is characterised by a state of persistent fever, inflammation and organ dysfunction following exposure to SARS-CoV-2 virus. It shares similar clinical features to Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. Like adult COVID-19 infection, profound inflammatory response significantly increases the risk of thromboembolism, which is a major cause of morbidity and mortality. In this review we share our experience, observation and prevention strategy with regard to thromboembolism in PIMS-TS. Method: Between the period of 14(th) March 2020 to 31(st) May 2020, Evelina London Children's Hospital admitted 68 patients with PIMS-TS from the South Thames Network. Patients were broadly treated with a combination of high dose aspirin and immunomodulation in the initial period. Realising its pro-thrombotic potential, from 1(st) May 2020, treatment strategy was changed to incorporate prophylactic subcutaneous low molecular weight heparin (dalteparin 100units/kg once daily) in combination with low dose aspirin (5mg/kg once daily, maximum 75mg) when a working diagnosis of PIMS-TS was made. We retrospectively collected data to understand the prevalence and pattern of thromboembolism in this cohort of patients. Results: Five patients (7.4%) developed thromboembolic complications during their acute illness with 6 recorded events overall. (Table 1) Three events happened without prophylactic anticoagulation cover. Four (5.9%) were cardiovascular/arterial events and 2 (2.9%) were venous thromboembolism. Those who required ventilation support and extracorporeal membrane oxygenation (ECMO) were associated with higher thrombotic rate using 2-tailed Fisher's exact test (ventilation: p=0.02; ECMO: p=0.004). One ischaemic cerebrovascular event resulted in death. Two bleeding events were recorded whilst on anticoagulation. One was iatrogenic following arterial line insertion and another a haemorrhagic transformation from an ischaemic stroke. Coagulation markers (fibrinogen and D-dimer) followed the overall pattern observed in inflammatory markers (ferritin and C-reactive protein) on admission, at peak values and at 2-week follow up, suggesting a connection between the degree of inflammation and hypercoagulability and inferring immunothrombosis. (Table 2) Peak ferritin and D-dimer levels were significantly higher in the group with thromboembolism using 2-tailed Mann-Whitney U test (ferritin: p=0.038; D-dimer: p=0.034). Conclusion: Thromboembolism needs to be considered as a significant complication in patients with a diagnosis of PIMS-TS. We observed more cardiovascular/arterial events than venous events, which coincided with the fact that PIMS-TS patients commonly develop cardiac involvement and coronary abnormalities. In addition to rapid correction of hyper-inflammatory state using immunomodulation, we suggest the consideration of low dose aspirin (5mg/kg once daily, maximum 75mg) and prophylactic dalteparin (100units/kg once daily) to prevent both arterial and venous thrombosis after careful individual assessment and exclusion of co-existing factors that can cause increased bleeding risk. This may be especially relevant in those with already raised ferritin and D-dimer levels on admission. [Figure: see text] DISCLOSURES: Inusa:Vertex: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Bluebird bio: Research Funding; Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau.
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spelling pubmed-83302672021-08-03 Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS) Lam, Ho Pui Jeff Alamelu, Jayanthi Brighouse, James Miller, Owen Lillie, Jonathan Inusa, Baba PD Blood 114.Hemoglobinopathies, Excluding Thalassemia-Clinical Introduction: Paediatric Inflammatory Multisystem Syndrome - temporally associated with SARS-CoV2 (PIMS-TS) is a newly described syndrome during the COVID-19 pandemic. It is characterised by a state of persistent fever, inflammation and organ dysfunction following exposure to SARS-CoV-2 virus. It shares similar clinical features to Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. Like adult COVID-19 infection, profound inflammatory response significantly increases the risk of thromboembolism, which is a major cause of morbidity and mortality. In this review we share our experience, observation and prevention strategy with regard to thromboembolism in PIMS-TS. Method: Between the period of 14(th) March 2020 to 31(st) May 2020, Evelina London Children's Hospital admitted 68 patients with PIMS-TS from the South Thames Network. Patients were broadly treated with a combination of high dose aspirin and immunomodulation in the initial period. Realising its pro-thrombotic potential, from 1(st) May 2020, treatment strategy was changed to incorporate prophylactic subcutaneous low molecular weight heparin (dalteparin 100units/kg once daily) in combination with low dose aspirin (5mg/kg once daily, maximum 75mg) when a working diagnosis of PIMS-TS was made. We retrospectively collected data to understand the prevalence and pattern of thromboembolism in this cohort of patients. Results: Five patients (7.4%) developed thromboembolic complications during their acute illness with 6 recorded events overall. (Table 1) Three events happened without prophylactic anticoagulation cover. Four (5.9%) were cardiovascular/arterial events and 2 (2.9%) were venous thromboembolism. Those who required ventilation support and extracorporeal membrane oxygenation (ECMO) were associated with higher thrombotic rate using 2-tailed Fisher's exact test (ventilation: p=0.02; ECMO: p=0.004). One ischaemic cerebrovascular event resulted in death. Two bleeding events were recorded whilst on anticoagulation. One was iatrogenic following arterial line insertion and another a haemorrhagic transformation from an ischaemic stroke. Coagulation markers (fibrinogen and D-dimer) followed the overall pattern observed in inflammatory markers (ferritin and C-reactive protein) on admission, at peak values and at 2-week follow up, suggesting a connection between the degree of inflammation and hypercoagulability and inferring immunothrombosis. (Table 2) Peak ferritin and D-dimer levels were significantly higher in the group with thromboembolism using 2-tailed Mann-Whitney U test (ferritin: p=0.038; D-dimer: p=0.034). Conclusion: Thromboembolism needs to be considered as a significant complication in patients with a diagnosis of PIMS-TS. We observed more cardiovascular/arterial events than venous events, which coincided with the fact that PIMS-TS patients commonly develop cardiac involvement and coronary abnormalities. In addition to rapid correction of hyper-inflammatory state using immunomodulation, we suggest the consideration of low dose aspirin (5mg/kg once daily, maximum 75mg) and prophylactic dalteparin (100units/kg once daily) to prevent both arterial and venous thrombosis after careful individual assessment and exclusion of co-existing factors that can cause increased bleeding risk. This may be especially relevant in those with already raised ferritin and D-dimer levels on admission. [Figure: see text] DISCLOSURES: Inusa:Vertex: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Bluebird bio: Research Funding; Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau. American Society of Hematology 2020-11-05 2021-08-03 /pmc/articles/PMC8330267/ http://dx.doi.org/10.1182/blood-2020-142424 Text en Copyright © 2020 American Society of Hematology. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle 114.Hemoglobinopathies, Excluding Thalassemia-Clinical
Lam, Ho Pui Jeff
Alamelu, Jayanthi
Brighouse, James
Miller, Owen
Lillie, Jonathan
Inusa, Baba PD
Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title_full Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title_fullStr Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title_full_unstemmed Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title_short Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
title_sort thrombosis and risk management in paediatric inflammatory multisystem syndrome - temporally associated with sars-cov2 (pims-ts)
topic 114.Hemoglobinopathies, Excluding Thalassemia-Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330267/
http://dx.doi.org/10.1182/blood-2020-142424
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