Abstract
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.
Highlights
Extracorporeal membrane oxygenation (ECMO) is used to treat critically ill patients suffering from acute respiratory and/or cardiac failure unresponsive to conventional treatment [1]
We present data from 33 patients treated with ECMO between September 2017 and April 2019; among which, 24 patients had flow cytometry performed on both day 1 and day 3
Two patients had VA ECMO converted to a VV configuration during the course of ECMO support, and another patient had VA ECMO converted to a combined VA/VV configuration
Summary
Extracorporeal membrane oxygenation (ECMO) is used to treat critically ill patients suffering from acute respiratory and/or cardiac failure unresponsive to conventional treatment [1]. Bleeding and thromboembolic events frequently occur during ECMO support, greatly affecting patient outcomes [5, 6]. Major bleeding is reported to occur in up to one third of adult ECMO patients [4, 7, 8], and reports of intracranial hemorrhage range from 5 to 20% [3, 9, 10]. Thromboembolic complications are generally less common with intracranial infarction reported to occur in up to 5% [3, 7, 9] and venous thrombosis in 7–10% of adult ECMO patients [7, 11]. Recent studies have investigated mechanisms in vitro that may affect platelet function during ECMO support, suggesting that platelets may become concurrently activated and impaired [13,14,15]
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