Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02002-5

The association of platelet dysfunction and mortality in ECMO patients

J. Chalupsky1, C. Olivier2, I. Bojti2, J.-S. Pooth2, G. Trummer3, C. Bode2, P. Diehl4, P. M. Siegel2

1Kardiologie und Angiologie I, Albert- Ludwigs-Universität Freiburg, Freiburg im Breisgau; 2Klinik für Kardiologie und Angiologie I, Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH, Freiburg im Breisgau; 3Klinik für Herz- und Gefäßchirurgie, Universitäts-Herzzentrum Freiburg - Bad Krozingen GmbH, Freiburg im Breisgau; 4Kardiologie, Ortenau-Klinikum Lahr-Ettenheim, Lahr/Schwarzwald;

Background: Extracorporeal membrane oxygenation (ECMO) is being increasingly used for critically ill patients suffering from cardiopulmonary failure but mortality in these patients remains high. Severe bleeding complications are common and associated with poor outcome. As platelets are important mediators in haemostasis and vascular inflammation, platelet dysfunction may play an important role. The aim of this study was to characterize platelet dysfunction and its relation to outcome in ECMO patients. Methods: We analysed the expression of the surface markers CD62P, CD63, activated GPIIb/IIIa, GPVI, GPIbα and platelet leukocyte aggregates at rest and in response to stimulation in patients receiving ECMO. Blood was sampled on day 1, 3 and after explantation of the ECMO system. Furthermore, we examined δ-granule release via a mepacrine assay, which allowed us to investigate an acquired δ-granule release deficiency. We compared the results to a group of healthy controls and patients with stable coronary artery disease and between survivors and non-survivors. Logistic regression was carried out to determine the association of different platelet markers with mortality. Results: We recruited 30 patients receiving ECMO, 15 healthy controls and 10 patients with stable coronary artery disease. Platelets from ECMO patients were severely dysfunctional as we found reduced expression of CD62P, CD63 and activated GPIIb/IIa and a reduced formation and platelet leukocyte aggregates in response to stimulation in ECMO patients, as well as a reduced expression of GPVI and GPIbα. According to mepacrine staining of δ-granules in platelets, granule release in response to stimulation was weaker in ECMO patients. In non-survivors, baseline expression of CD63 was higher and expression of activated GPIIb/IIIa in response to stimulation was lower and logistic regression analysis demonstrated that these markers were associated with mortality. Conclusion: Platelets from ECMO patients are severely dysfunctional placing patients at risk of severe 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. In the future, CD63 and activated GPIIb/IIIa may therefore serve as novel prognostic biomarkers guiding early clinical decision making for ECMO patients.   Fig. 1: Expression of activated GPIIb/IIIa in patients receiving extracorporeal membrane oxygenation (ECMO) vs. controls determined on resting (baseline), TRAP- or ADP-stimulated platelets using the conformation-specific antibody PAC-1. Blood was sampled from ECMO patients on day 1, day 3 and after ECMO explantation (Post). Expression of activated GPIIb/IIIa was compared to healthy controls (Healthy) and patients with coronary artery disease (CAD). The number of ECMO patients remaining at each time point and the number of control patients are indicated below. ns, not significant, *p<0.05, **p<0.01, ***p<0.001

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