Factors XI and XII in extracorporeal membrane oxygenation: longitudinal profile in children

Joppe Drop; Natasha Letunica; Suelyn Van Den Helm; C Heleen van Ommen; Enno Wildschut; Matthijs de Hoog; Joost van Rosmalen; Rebecca Barton; Hui Ping Yaw; Fiona Newall; Stephen B Horton; Roberto Chiletti; Amy Johansen; Derek Best; Joanne McKittrick; Warwick Butt; Yves d'Udekem; Graeme MacLaren; Matthew D Linden; Vera Ignjatovic; Chantal Attard; Paul Monagle

doi:10.1016/j.rpth.2023.102252

Factors XI and XII in extracorporeal membrane oxygenation: longitudinal profile in children

Res Pract Thromb Haemost. 2023 Nov 4;7(8):102252. doi: 10.1016/j.rpth.2023.102252. eCollection 2023 Nov.

Authors

Joppe Drop^{1

2

3}, Natasha Letunica³, Suelyn Van Den Helm^{3

4}, C Heleen van Ommen¹, Enno Wildschut², Matthijs de Hoog², Joost van Rosmalen^{5

6}, Rebecca Barton^{3

4

7}, Hui Ping Yaw³, Fiona Newall^{3

4

7}, Stephen B Horton^{4

8}, Roberto Chiletti^{9

10

11}, Amy Johansen^{9

10}, Derek Best^{9

10}, Joanne McKittrick⁹, Warwick Butt^{4

9

10

11}, Yves d'Udekem¹², Graeme MacLaren¹³, Matthew D Linden¹⁴, Vera Ignjatovic^{3

4

15

16}, Chantal Attard^{3

4}, Paul Monagle^{3

4

7

17}

Affiliations

¹ Department of Paediatrics, Division of Paediatric Hematology, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, South Holland, The Netherlands.
² Department of Paediatrics, Division of Paediatric Intensive Care and Paediatric Surgery, Erasmus Medical Centre - Sophia Children's Hospital, Rotterdam, South Holland, The Netherlands.
³ Haematology Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
⁴ Department of Paediatrics, The University of Melbourne, Melbourne, Victoria, Australia.
⁵ Department of Biostatistics, Erasmus University Medical Center, Rotterdam, South Holland, The Netherlands.
⁶ Department of Epidemiology, Erasmus University Medical Center, University Medical Center Rotterdam, Rotterdam, South Holland, The Netherlands.
⁷ Department of Clinical Haematology, The Royal Children's Hospital, Melbourne, Victoria, Australia.
⁸ Department of Cardiac Surgery, The Royal Children's Hospital, Melbourne, Victoria, Australia.
⁹ Department of Intensive Care, The Royal Children's Hospital, Melbourne, Victoria, Australia.
¹⁰ Paediatric Intensive Care Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
¹¹ Department of Critical Care, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Department of Cardiac Surgery, Children's National Heart Institute, Washington DC, USA.
¹³ Cardiothoracic Intensive Care Unit, National University Health System, Singapore.
¹⁴ School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.
¹⁵ Johns Hopkins All Children's Institute for Clinical and Translational Research, St Petersburg, Florida, USA.
¹⁶ Department of Paediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
¹⁷ Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia.

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) is used in children with cardiopulmonary failure. While the majority of ECMO centers use unfractionated heparin, other anticoagulants, including factor XI and factor XII inhibitors are emerging, which may prove suitable for ECMO patients. However, before these anticoagulants can be applied in these patients, baseline data of FXI and FXII changes need to be acquired.

Objectives: This study aimed to describe the longitudinal profile of FXI and FXII antigenic levels and function before, during, and after ECMO in children.

Methods: This is a prospective observational study in neonatal and pediatric patients with ECMO (<18 years). All patients with venoarterial ECMO and with sufficient plasma volume collected before ECMO, on day 1 and day 3, and 24 hours postdecannulation were included. Antigenic levels and functional activity of FXI and FXII were determined in these samples. Longitudinal profiles of these values were created using a linear mixed model.

Results: Sixteen patients were included in this study. Mean FXI and FXII antigenic levels (U/mL) changed from 7.9 and 53.2 before ECMO to 6.0 and 34.5 on day 3 and they recovered to 8.8 and 39.4, respectively, after stopping ECMO. Function (%) of FXI and FXII decreased from 59.1 and 59.0 to 49.0 and 50.7 on day 3 and recovered to 66.0 and 54.4, respectively.

Conclusion: This study provides the first insights into changes of the contact pathway in children undergoing ECMO. FXI and FXII antigen and function change during ECMO. Results from this study can be used as starting point for future contact pathway anticoagulant studies in pediatric patients with ECMO.

Keywords: extracorporeal membrane oxygenation; factor XI; factor XII; infant; newborn.