Background: Extracorporeal membrane oxygenation (ECMO) is associated with platelet dysfunction, coagulopathy, bleeding, and thrombosis. Additionally, ECMO duration is an important factor affecting the outcome of paediatric patients. Understanding haemostasis and platelet-specific changes during ECMO is essential to improve clinical outcomes.

Aims: To determine the platelet phenotype and measure platelet function and their associations with clinical events during paediatric ECMO.

Methods: This study was approved by the Royal Children’s Hospital (RCH) Human Research Ethics Committee. Written informed consent was obtained from parents/guardians. Blood samples were collected from the arterial line of paediatric veno-arterial ECMO (VA-ECMO) patients. Platelet phenotype and function [response to thrombin receptor activated peptide-6 (TRAP-6)] were examined using whole blood flow cytometry and results at days 2 and 5 of ECMO were compared using paired t-tests.

Results: 18 VA-ECMO patients aged between 1 day and 15 years (median age 9 months) with median ECMO duration of 8 days were analysed.  56% of patients had at least one major bleed and 33% had at least one thrombosis during ECMO. Platelet fibrinogen receptor expression decreased by day 5 compared to day 2 of ECMO whereas von Willebrand Factor (VWF) expression increased (Figure 1). There were no associated changes in plasma fibrinogen or VWF. This decrease in fibrinogen receptor expression was observed regardless of bleeding or thrombosis status. However, the increase in VWF receptor expression was only observed in patients with bleeding or without a thrombosis (Figure 2). Platelet function decreased by day 5, as indicated by lower P-selectin, PAC-1 and CD63 Area Under the Curve (AUCs) values  in response to TRAP-6 (Figure 1).

Changes in platelet phenotype and function between day 2 and day 5 of VA-ECMO (AUC = Area Under the Curve; MFI = Median Fluorescence Intensity; VWF = von Willebrand factor)

 Changes in platelet phenotype between day 2 and day 5 of VA-ECMO according the bleeding and thrombosis status (AUC = Area Under the Curve; MFI = Median Fluorescence Intensity; VWF = von Willebrand Factor; Major bleeding = at least one major bleed during ECMO including >4ml/kg/hr for >4hours, intracranial or pulmonary haemorrhage, or gastrointestinal bleed requiring endoscope or surgical intervention, or surgical site bleed requiring re-operation; Thrombosis = Thrombosis (venous or arterial) requiring acute intervention or formal anticoagulation beyond ECMO , radiologically proven CNS embolic stroke or ECMO circuit thrombosis requiring circuit change)

Conclusions: Understanding changes in platelet phenotype and function during ECMO can provide insights into the pathophysiology leading to bleeding and/or thrombosis. For example, our results suggest reductions in platelet function over time may be one mechanism that contributes to bleeding on ECMO.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-fibrinogen-receptor-expression-and-platelet-function-decreases-as-duration-of-ecmo-increases-in-paediatric-veno-arterial-ecmo-patients/