Abstract
Extracorporeal membrane oxygenation (ECMO) is used for patients with cardiopulmonary failure and is associated with severe bleeding and poor outcome. Platelet dysfunction may be a contributing factor. The aim of this prospective observational study was to characterize platelet dysfunction and its relation to outcome in ECMO patients. Blood was sampled from thirty ECMO patients at three timepoints. Expression of CD62P, CD63, activated GPIIb/IIIa, GPVI, GPIbα and formation platelet-leukocyte aggregates (PLA) were analyzed at rest and in response to stimulation. Delta granule storage-pool deficiency and secretion defects were also investigated. Fifteen healthy volunteers and ten patients with coronary artery disease served as controls. Results were also compared between survivors and non-survivors. Compared to controls, expression of platelet surface markers, delta granule secretion and formation of PLA was reduced, particularly in response to stimulation. Baseline CD63 expression was higher and activated GPIIb/IIIa expression in response to stimulation was lower in non-survivors on day 1 of ECMO. Logistic regression analysis revealed that these markers were associated with mortality. In conclusion, platelets from ECMO patients are severely dysfunctional predisposing patients to bleeding complications and poor outcome. Platelet dysfunction on day 1 of ECMO detected by the platelet surface markers CD63 and activated GPIIb/IIIa is associated with mortality. CD63 and activated GPIIb/IIIa may therefore serve as novel prognostic biomarkers, but future studies are required to determine their true potential.
Highlights
Extracorporeal membrane oxygenation (ECMO) is being increasingly used for critically ill patients requiring hemodynamic or respiratory support [1]
This study reveals multiple signs of platelet dysfunction in ECMO patients and indicates that platelet dysfunction on day 1 of ECMO as determined by CD63 or activated GPIIb/ IIIa is associated with mortality
To the best of our knowledge, this study is the first to establish a link between platelet dysfunction and mortality in patients receiving ECMO
Summary
Extracorporeal membrane oxygenation (ECMO) is being increasingly used for critically ill patients requiring hemodynamic or respiratory support [1]. Veno-venous (VV-) ECMO is used for patients with respiratory failure and has gained importance during the ongoing COVID-19 pandemic [2]. Mortality is high in ECMO patients [5] and specific ECMO-related complications, for example bleeding and thrombotic complications contribute to the poor outcome [6, 7]. Platelet surface expression of P-selectin (CD62P), CD63 and the activated conformation of GPIIb/ IIIa (detected via the activation-specific antibody PAC1) and changes in response to stimulants like adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) can be assessed using flow cytometry [9]. Granule release occurs in response to thrombin stimulation and can be monitored by flow cytometry in
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