BIO14: Platelet energy metabolism in an in-vitro ECMO model

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) exposes blood to mechanical shear stress and artificial surfaces, leading to platelet activation and thrombosis. We hypothesize that ECMO-induced platelet activation leads to changes in platelet energy metabolism. Methods: Based on an in vitro ECMO model (Cardiohelp platform; HLS Advanced 5.0 Oxygenator), human whole blood was circulated at low (1 L/min) or nominal flow (4L/min) for 6 hours. A static control sample was drawn after priming and held in the same tubing at 37 °C. Experiments were terminated if clot formation caused device failure. Samples were drawn at baseline as well as hourly throughout the experiment (T0 – T6) and assessed for cell counts and intracellular levels of bioenergetic intermediates, which were normalized to platelet count. Results: Preliminary data documents that 83% of ECMO runs completed 6 hours of perfusion. One nominal ECMO run was terminated due to clot formation after 5 hours. We found a statistically significant difference in platelet ATP levels after 6 hours between the control and the nominal group (181 nM ± 13 vs 107 nM ± 11, p = 0.02). Furthermore, we saw a statistically significant difference in ADP levels at T6 between the control group and the nominal group (517 nM ± 45 vs 255 nM ± 16, p = 0.001) as well as between the control group and the low-flow-group (330 nM ± 9, p = 0.001). We observed a trend in difference between low and nominal flow groups for ATP and ADP. Conclusion: This preliminary analysis indicates that ECMO pump flow rate effects on ATP and ADP levels in platelets. These insights into energy metabolism in platelets exposed to ECMO might lead to novel therapeutical approaches to prevent clotting events during ECMO.