Thrombosis and Risk Management in Paediatric Inflammatory Multisystem Syndrome - Temporally Associated with Sars-CoV2 (PIMS-TS)
Autor: | James Brighouse, Jonathan Lillie, Baba Inusa, Jayanthi Alamelu, Owen Miller, Ho Pui Jeff Lam |
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Rok vydání: | 2020 |
Předmět: |
medicine.medical_specialty
Aspirin business.industry medicine.drug_class medicine.medical_treatment Immunology Organ dysfunction Low molecular weight heparin Cell Biology Hematology medicine.disease Biochemistry Thrombosis Venous thrombosis Internal medicine Macrophage activation syndrome medicine Extracorporeal membrane oxygenation Kawasaki disease medicine.symptom 114.Hemoglobinopathies Excluding Thalassemia-Clinical business medicine.drug |
Zdroj: | Blood |
ISSN: | 1528-0020 0006-4971 |
DOI: | 10.1182/blood-2020-142424 |
Popis: | 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 14th March 2020 to 31st 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 1st 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. 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. |
Databáze: | OpenAIRE |
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