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Observational Study
. 2022 Apr;53(3):712-721.
doi: 10.1007/s11239-021-02562-9. Epub 2021 Sep 16.

Early platelet dysfunction in patients receiving extracorporeal membrane oxygenation is associated with mortality

Patrick Malcolm Siegel  1 , Julia Chalupsky  2 , Christoph B Olivier  2 , István Bojti  2 , Jan-Steffen Pooth  3 , Georg Trummer  3 , Christoph Bode  2 , Philipp Diehl  2
Affiliations
Observational Study

Early platelet dysfunction in patients receiving extracorporeal membrane oxygenation is associated with mortality

Patrick Malcolm Siegel et al. J Thromb Thrombolysis. 2022 Apr.

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.

Keywords: Critical care; Extracorporeal membrane oxygenation; Hemorrhage; Mortality; Platelets.

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Conflict of interest statement

G.T. is founder, shareholder, and part time employee of Resuscitec Freiburg, Germany. J.P. is a part time employee of Resuscitec Freiburg, Germany. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Platelet expression of CD62P in patients receiving extracorporeal membrane oxygenation (ECMO) compared to controls. CD62P expression was analyzed by flow cytometry on resting (baseline), thrombin receptor activating peptide (TRAP)-stimulated and adenosine diphosphate (ADP)-stimulated platelets. Blood was sampled from ECMO patients on day1, day 3 and after ECMO explantation (Post). CD62P expression on platelets was compared to healthy controls (Healthy) and patients with coronary artery disease (CAD). a, Baseline CD62P expression was similar in ECMO patients and controls. CD62P expression in response to TRAP (b) and ADP (c) stimulation was lower in ECMO patients. The number of ECMO patients remaining at each time point and the number of control patients are indicated below. Data are presented as mean ± standard error of the mean. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 2
Fig. 2
Platelet expression of CD63 in patients receiving extracorporeal membrane oxygenation (ECMO) compared to controls. CD63 expression was analyzed by flow cytometry on resting (baseline), thrombin receptor activating peptide (TRAP)-stimulated and adenosine diphosphate (ADP)-stimulated platelets. Blood was sampled from ECMO patients (ECMO) on day 1, day 3 and after ECMO explantation (Post). CD63 expression on platelets was compared to healthy controls (Healthy) and patients with coronary artery disease (CAD). a, Baseline CD63 expression was significantly elevated on platelets from ECMO patients compared to controls. b, CD63 expression in response to TRAP was lower in ECMO patients compared to healthy controls. c, CD63 expression in response to ADP stimulation was similar in ECMO patients and controls. The number of ECMO patients remaining at each time point and the number of control patients are indicated below. Data are presented as mean ± standard error of the mean. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 3
Fig. 3
Expression of activated GPIIb/IIIa in patients receiving extracorporeal membrane oxygenation (ECMO) compared to controls. Expression of activated GPIIb/IIIa was analyzed by flow cytometry on resting (baseline), thrombin receptor activating peptide (TRAP)-stimulated and adenosine diphosphate (ADP)-stimulated platelets using the conformation specific antibody PAC-1. Blood was sampled from ECMO patients (ECMO) on day 1, day 3 and after ECMO explantation (Post). Expression of activated GPIIb/IIIa on platelets was compared to healthy controls (Healthy) and patients with coronary artery disease (CAD). a, Baseline expression of activated GPIIb/IIIa did not significantly differ between ECMO patients or controls. b, Expression of activated GPIIb/IIIa in response to TRAP stimulation was significantly lower in ECMO patients at all time points compared to healthy controls and CAD patients. c, Expression of activated GPIIb/IIIa in response to ADP stimulation in ECMO patients was also significantly lower compared to controls. The number of ECMO patients remaining at each time point and the number of control patients are indicated below. Data are presented as mean ± standard error of the mean. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001
Fig. 4
Fig. 4
Levels of platelet leukocyte aggregates (PLA) in patients receiving extracorporeal membrane oxygenation (ECMO) compared to controls. The percentage of CD61+/CD45+ PLA of all CD45+ leukocytes is presented. PLA were analyzed at rest (‘baseline’) and in response to simulation with adenosine diphosphate (ADP) and phorbol 12-myristate 13-acetate (‘stimulated’). Blood was sampled from ECMO patients (ECMO) on day 1, day 3 and after ECMO explantation (Post). PLA in ECMO patients were compared to healthy controls (Healthy) and patients with coronary artery disease (CAD). a, baseline PLA levels were similar in ECMO patients and healthy controls. CAD patients had higher levels of PLA. b, PLA formation in response to stimulation was significantly reduced in ECMO patients and reached significance at all time points compared to healthy controls. The number of ECMO patients remaining at each time point and the number of control patients are indicated below. Data are presented as mean ± standard error of the mean. ns, not significant, *p < 0.05, **p < 0.01, ***p < 0.001
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