The Relationship between Platelet Phenotype and Function with Clinical Outcomes in 57 Paediatric Veno-Arterial ECMO Patients

S. Van Den Helm¹, H.P. Yaw^1,2, N. Letunica¹, R. Barton^1,2,3, F. Newall^1,2,3, S. Horton^2,4, G. MacLaren^1,5,6, R. Chiletti^5,7, A. Johansen^5,7, D. Best^5,7, J. McKittrick⁵, W. Butt^2,5,7, Y. d'Udekem^1,2,8, M. Linden⁹, P. Monagle^1,2,3, V. Ignjatovic^1,2

¹Murdoch Children's Research Institute, Haematology Research, Melbourne, Australia, ²University of Melbourne, Department of Paediatrics, Melbourne, Australia, ³The Royal Children's Hospital, Department of Clinical Haematology, Melbourne, Australia, ⁴The Royal Children's Hospital, Perfusion Department, Melbourne, Australia, ⁵The Royal Children's Hospital, Department of Intensive Care, Melbourne, Australia, ⁶National University Health System, Cardiothoracic Intensive Care Unit, Queenstown, Singapore, ⁷Murdoch Children's Research Institute, Paediatric Intensive Care Research, Melbourne, Australia, ⁸The Royal Children's Hospital, Department of Cardiac Surgery, Melbourne, Australia, ⁹The University of Western Australia, School of Biomedical Sciences, Perth, Australia

Abstract Number: PB1245

Meeting: ISTH 2020 Congress

Theme: Pediatrics » Bleeding in Neonates and Children

Background: Extracorporeal membrane oxygenation (ECMO) as a form of life support and the underlying diseases are associated with platelet dysfunction and coagulopathy. Maintaining haemostasis in ECMO patients is challenging. Understanding haemostasis and platelet function in the context of ECMO, particularly their association with patient outcomes, is essential in improving outcomes for children requiring this support.

Aims: This study aimed to determine the association between platelet phenotype and function, and bleeding and clotting outcomes in children on ECMO.

Methods: This study was approved by the Royal Children’s Hospital (RCH) Ethics in Human Research Committee and written informed consent was obtained from parents. ECMO patients were recruited from the RCH Paediatric Intensive Care Unit (PICU) from March 2017 to December 2019. Samples were collected from the arterial line of 57 neonates and children placed on veno-arterial ECMO (VA-ECMO) within 24 hours of ECMO initiation. Whole blood flow cytometry was used to measure markers of platelet phenotype and function (response to thrombin receptor activated peptide-6 (TRAP-6)). Clinical data was recorded and logistic regression was used to determine associations between platelet phenotype and function, and bleeding and thrombosis.

Results: 57 patients (Table 1) were recruited between the age of 1 day and 18 years (median age of 2.2 months). The median duration of VA-ECMO was 5 days (range 1 to 112 days). A significant association between both increased basal platelet activation and response to TRAP-6 with major bleeding was found using CD63, a lysosome release indicator (p=0.0033 and p=0.0192 respectively, Table 2).

Total Number of Patients	n = 57
Age	Neonates (0 – 30 days)	24 (42%)
	Infants (31 days – 1 year)	11 (19%)
	Children (1 – 18 years)	22 (39%)
Gender	Male	29 (51%)
	Female	28 (49%)
Cannulation site	Central	40 (70%)
	Peripheral	17 (30%)
At least one major bleed	>4ml/kg/hr for >4hrs Intracranial or pulmonary haemorrhage Gastrointestinal bleed requiring endoscope or surgical intervention Surgical site bleed requiring re-operation	25 (44%)
At least one thrombosis	Thrombosis (venous or arterial) requiring acute intervention or formal anticoagulation beyond ECMO Radiologically proven CNS embolic stroke ECMO circuit thrombosis requiring circuit change	8 (14%)

[Table 1. VA-ECMO patient demographics]

Major Bleeding	Odds Ratio	Standard Error	p-value	[95% Confidence Interval]
CD61 MFI	1.000	0.0001	0.0905	1.000	1.000
CD42b MFI	1.000	0.0001	0.3251	1.000	1.000
GPVI MFI	1.000	0.0002	0.8195	1.000	1.000
Basal CD62P %	0.877	0.1902	0.5320	0.573	1.341
Basal PAC1 %	1.041	0.0279	0.1093	0.988	1.097
Basal CD63%	1.258	0.1091	0.0033	1.062	1.491
Activated CD62P (AUC)	1.017	0.0138	0.2006	0.990	1.045
Activated PAC1 (AUC)	1.020	0.0106	0.0519	0.999	1.041
Activated CD63 (AUC)	1.048	0.023	0.0192	1.003	1.094

[Table 2. Relationship between platelet phenotype and function and major bleeding. (MFI = Median Fluorescence Intensity; AUC = Area Under the Curve)]

Conclusions: An association between increased basal activation state and the ability to further activate platelets with bleeding in paediatric VA-ECMO patients was identified. CD63 could potentially be used as an early biomarker of bleeding events in ECMO patients. Analysing platelets by flow cytometry could benefit ECMO patients by facilitating early intervention to prevent bleeding and clotting events.

To cite this abstract in AMA style:

Van Den Helm S, Yaw HP, Letunica N, Barton R, Newall F, Horton S, MacLaren G, Chiletti R, Johansen A, Best D, McKittrick J, Butt W, d'Udekem Y, Linden M, Monagle P, Ignjatovic V. The Relationship between Platelet Phenotype and Function with Clinical Outcomes in 57 Paediatric Veno-Arterial ECMO Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/the-relationship-between-platelet-phenotype-and-function-with-clinical-outcomes-in-57-paediatric-veno-arterial-ecmo-patients/. Accessed December 6, 2023.

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