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

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.

SUBMITTER: Siegel PM

PROVIDER: S-EPMC8444511 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used for critically ill patients requiring hemodynamic support but has been shown to induce an inflammatory response syndrome potentially leading to severe complications and poor outcome. Monocytes are comprised of different subsets and play a central role in the innate immune system. The unique small binding proteins, Designed Ankyrin Repeat Protein "F7" and single chain variable fragment "MAN-1," specifically detect the activated conformation of the leukocyte integrin Mac-1 enabling the highly sensitive detection of monocyte activation status. The aim of this study was to characterize monocyte function and heterogeneity and their association with outcome in VA-ECMO patients. Methods: VA-ECMO patients were recruited from the ICUs of the University Hospital in Freiburg, Germany. Blood was sampled on day 0 and day 3 after VA-ECMO placement, after VA-ECMO explantation and from healthy controls. Monocyte subset distribution, baseline activation and stimulability were analyzed by flow cytometry using the unique small binding proteins F7 and MAN-1 and the conventional activation markers CD163, CD86, CD69, and CX3CR1. Furthermore, expression of monocyte activation markers in survivors and non-survivors on day 0 was compared. Simple logistic regression was conducted to determine the association of monocyte activation markers with mortality. Results: Twenty two patients on VA-ECMO and 15 healthy controls were recruited. Eleven patients survived until discharge from the ICU. Compared to controls, baseline monocyte activation was significantly increased, whereas stimulability was decreased. The percentage of classical monocytes increased after explantation, while the percentage of intermediate monocytes decreased. Total, classical, and intermediate monocyte counts were significantly elevated compared to controls. On day 0, baseline binding of F7 was significantly lower in non-survivors than survivors. The area under the ROC curve associated with mortality on day 0 was 0.802 (p = 0.02). Conclusions: Distribution of monocyte subsets changes during VA-ECMO and absolute classical and intermediate monocyte counts are significantly elevated compared to controls. Monocytes from VA-ECMO patients showed signs of dysfunction. Monocyte dysfunction, as determined by the unique tool F7, could be valuable for predicting mortality in patients receiving VA-ECMO and may be used as a novel biomarker guiding early clinical decision making in the future.

Project description:Objective: Hemorrhagic and thromboembolic complications are common during support with extracorporeal membrane oxygenation (ECMO). As platelets play a pivotal role in hemostasis, we aimed to clarify how ECMO support affects platelet function. Methods: We included 33 adult patients undergoing ECMO support at a tertiary ECMO referral center at Aarhus University Hospital, Denmark. Blood samples were collected on the first morning following ECMO initiation, and subsequently every morning until the 7th (±1) day. Platelet aggregation was evaluated by whole blood impedance aggregometry (Multiplate® Analyzer) using adenosine diphosphate (ADPtest), arachidonic acid (ASPItest), and thrombin-receptor-agonist-peptide-6 (TRAPtest) as agonists. A new model was applied, taking platelet count into consideration in interpretation of impedance aggregometry analyses. On the 1st and 3rd day, platelet activation was assessed by flow cytometry (Navios) using collagen-related peptide, ADP, TRAP, and arachidonic acid as agonists. Results: Blood samples from all 33 patients were analyzed on day 1 of ECMO support; 24 patients were still receiving ECMO and analyzed on day 3; 12 patients were analyzed on day 7 (±1). After ECMO initiation, platelet counts decreased significantly (p < 0.002) and remained low during ECMO support. ECMO patients demonstrated significantly reduced platelet aggregation on day 1 compared with healthy controls (all p < 0.001). However, when taking platelet count into consideration, platelet aggregation relative to platelet count did not differ from healthy controls. Flow cytometry analyses demonstrated impaired platelet activation in ECMO patients on day 1 compared with healthy controls (all p < 0.03). No substantial difference was found in platelet activation from day 1 to day 3 on ECMO support. Conclusions: Employing impedance aggregometry and flow cytometry, we found both impaired platelet aggregation and decreased platelet activation on day 1 of ECMO support compared with healthy controls. However, platelet aggregation was not impaired, when interpreted relative to the low platelet counts. Furthermore, levels of bound fibrinogen, on the surface of activated platelets in ECMO patients, were higher than in healthy controls. Together, these findings suggestively oppose that platelets are universally impaired during ECMO support. No marked difference in activation from day 1 to day 3 was seen during ECMO support.

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

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