Platelet-derived microparticles generated by neonatal extracorporeal membrane oxygenation systems

Abstract

Current anticoagulation strategies do not eliminate thromboembolic stroke or limb loss during neonatal extracorporeal membrane oxygenation (ECMO), a form of cardiopulmonary bypass (CPB). In adults, CPB surgery generates prothrombotic platelet-derived microparticles (PMPs), submicron membrane vesicles released from activated platelets. However, information on PMP generation in neonatal ECMO systems is lacking. The objective of this study was to compare PMP generation in five different neonatal ECMO systems, using a simulated circuit with swine blood at 300 ml/min for 4 hours. Systems were composed of both newer components (centrifugal pump and hollow-fiber oxygenator) and traditional components (roller-head pump and silicone membrane oxygenator). Free plasma hemoglobin levels were measured as an indicator of hemolysis and flow cytometry-measured PMP. Hemolysis generated in all ECMO systems was similar to that observed in noncirculated static blood (p = 0.48). There was no difference in net PMP levels between different oxygenators with a given pump. In contrast, net PMP generation in ECMO systems with a centrifugal pump was at least 2.5 times greater than in roller-head pump systems. This was significant when using either a hollow-fiber (p < 0.005) or a silicone membrane (p < 0.05) oxygenator. Future studies are needed to define the relationship between pump-generated PMP and thrombosis.

Figures

Figure 1

Neonatal in vitro ECMO model. A graphical depiction of a test circuit adapted from a previous study, which includes each of the in vitro circuit components that include the reservoir bag, pump, and oxygenator. Blood is drained from the reservoir bag, into the pump, pushed through the oxygenator, across an arterial catheter, and returns to the reservoir bag. To simulate the arterial resistance of an actual patient, an arterial catheter connected the oxygenator to the blood reservoir.

Figure 2

Effect of neonatal ECMO systems on free plasma hemoglobin (fPH) levels. A: Silicone oxygenator systems. B: Hollow-fiber oxygenator systems. Data represent the mean ± SE (n = 3 independent experiments).

Figure 3

Effect of neonatal ECMO systems on the normalized index of hemolysis (NIH). NIH values of each neonatal ECMO system in g/L. Data represent the mean ± SE (n = 3 independent experiments) except in CPQ system (n = 4 independent experiments). CPQ, Centrifugal + Pediatric Oxygenator.

Figure 4

Effect of neonatal ECMO systems on the generation of platelet-derived microparticles (PMPs). A: Silicone oxygenator systems. B: Hollow-fiber oxygenator systems. Data represent the mean ± SE (n = 3 independent experiments).