To the Editor: Fraile Navarro and colleagues1 recently published 20 recommendations for the treatment of coronavirus disease 2019 (COVID‐19) in children and adolescents from the National COVID‐19 Clinical Evidence Taskforce.
For the paediatric inflammatory multisystem syndrome (PIMS‐TS) recommendations, the Taskforce convened an expert advisory group.1 In the absence of clinical trials, the panel considered peer‐reviewed guidelines and cohort studies to formulate consensus recommendations.1 However, they deferred providing any guidance to help clinicians prevent thromboembolism. We suggest the Taskforce consider the same approach for paediatric anticoagulation guidance.
COVID‐19 is associated with marked coagulation activation and hypercoagulability in children.2,3 Life‐threatening pulmonary embolus requiring thrombolysis has been encountered in Australian adolescents hospitalised with COVID‐19.
A retrospective cohort study published in 2021 found that 2.1% of children hospitalised with symptomatic COVID‐19 infection and 6.5% of those with PIMS‐TS developed thrombosis.4 Thrombosis occurred more frequently in children aged 12 years and over who had central lines, PIMS‐TS, or an underlying oncological diagnosis. A D‐dimer of more than five times the upper limit of normal was significantly associated with thrombosis.4
The authors refer to “paediatric guidelines published in the US”, which are published on behalf of the Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee of the International Society of Thrombosis and Haemostasis; these adapt current consensus prophylaxis guidelines to include COVID‐19‐specific features.5
In deferring making specific recommendations, the authors suggested using existing local thromboprophylaxis guidelines. The Royal Children’s Hospital, Melbourne and the Sydney Children’s Hospital, Randwick have both independently developed COVID‐19‐specific thromboprophylaxis guidelines (that are very closely aligned),6,7 as have many other centres globally because previous local thromboprophylaxis guidelines are inadequate for COVID‐19‐associated thrombotic coagulopathy. The Melbourne/Sydney guidelines advise baseline coagulation testing in hospitalised children with COVID‐19, incorporating D‐dimer to assist risk assessment, twice‐daily enoxaparin and anti‐Xa monitoring/dose titration.6,7 These could be provided as supplemental material in these living guidelines.
The COVID‐19 anticoagulation in Children–Thromboprophylaxis (COVAC‐TP) trial — a phase 2 single‐arm study looking at 40 children who will receive monitored, low dose, twice‐daily enoxaparin (ClinicalTrials.gov Identifier NCT04354155) — will not change the level of evidence, so waiting for completion of this trial does not seem appropriate.
- 1. Fraile Navarro D, Tendal B, Tingay D, et al. Clinical care of children and adolescents with COVID‐19: recommendations from the National COVID‐19 Clinical Evidence Taskforce. Med J Aust 2022; 216: 255‐263. https://www.mja.com.au/journal/2022/216/5/clinical‐care‐children‐and‐adolescents‐covid‐19‐recommendations‐national‐covid
- 2. Chima M, Williams D, Thomas NJ, Krawiec C. COVID‐19‐associated pulmonary embolism in pediatric patients. Hosp Pediatr 2021; 11: e90‐e94.
- 3. Mitchell WB, Davila J, Keenan J, et al. Children and young adults hospitalized for severe COVID‐19 exhibit thrombotic coagulopathy. Pediatr Blood Cancer 2021; 68: e28975.
- 4. Whitworth H, Sartain SE, Kumar R, et al. Rate of thrombosis in children and adolescents hospitalized with COVID‐19 or MIS‐C. Blood 2021; 138: 190‐198.
- 5. Goldenberg NA, Sochet A, Albisetti M, et al. Consensus‐based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID‐19‐related illness. J Thromb Haemost 2020; 18: 3099‐3105.
- 6. Royal Children’s Hospital Melbourne. Clinical Practice Guidelines. COVID clinical management guidelines package (RCH). https://www.rch.org.au/uploadedFiles/Main/Content/clinicalguide/guideline_index/RCH‐COVID‐clinical‐management‐guidelines‐package.pdf (viewed Apr 2022).
- 7. Sydney Children’s Hospital. Thromboprophylaxis — children with COVID‐19 infection and multi‐inflammatory syndrome (MIS‐C). https://www.schn.health.nsw.gov.au/files/attachments/s128v1_thromboprophylaxis_children_with_covid19_infection_and_mis‐c.pdf (viewed Apr 2022).
We thank Professor Paul Monagle for his scientific advice and critical review of this letter.
No relevant disclosures.