Oxygenator Thrombogenicity: Pump-induced von Willebrand Factor Elongation as the Key Parameter (vWFOx)

• Applicant: Dr. Johanna Clauser
• Subject Area: Biomedical Systems Technology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576770669

Extracorporeal membrane oxygenation (ECMO) is used for critically ill patients in emergency situations, when acute lung and/or cardiac failure occur. Although being a potentially life-saving measure, adverse events such as oxygenator dysfunction due to clotting or bleeding events occur frequently. In this context, the von Willebrand factor (vWF) plays a central role as it is essential for the maintenance of coagulation in the event of vascular injury. It mediates the adhesion of platelets to the subendothelial matrix and contributes to the aggregation of platelets, especially under conditions of high shear stress in arterial vessels. However, when shear stresses increase far above 5000 s-1, unfolding and subsequent proteolysis of vWF results in dysfunction and loss of hemostatic maintenance. In ECMO circuits, high shear stresses above the critical unfolding threshold are applied to the blood by the pump. Additionally, huge artificial surface areas are present by the fiber bundle of the oxygenator, thereby presenting a high risk for vWF adhesion and subsequent platelet activation and coagulation initiation. Consequently, bleeding due to impaired vWF function, and thrombosis due to its interaction with artificial surfaces pose a major challenge in the management of ECMO therapy. We hypothesize that vWF, which was unfolded in the pump, may refold before entering the oxygenator, depending on the distance between pump and oxygenator and the shear stresses in the tubing between. In a complete or partially folded state, vWF does not expose binding sites for artificial material and platelet binding, thus reducing the thrombogenic potential of the oxygenator and the complete ECMO circuit. In contrast, if entering the oxygenator unfolded, vWF may easily attach to the membrane fibers promoting platelet adhesion, activation, and coagulation. To test our hypothesis, we first use a live imaging in-vitro approach. Using microfluidic channel experiments, the behavior of vWF is visualized in real time, measuring refolding times and distances. Additionally, live cell imaging experiments on a microchip will visualize vWF behavior, measuring refolding times and distances. Based on the acquired parameter set, two pump-oxygenator distances are chosen for the following in-vitro experiments. First, experiments are performed with isolated vWF in buffer solution and analyses focus solely on vWF activity, quantity and attachment. Second, whole blood experiments provide results on the impact of vWF unfolding and fiber mat binding on the complete coagulation cascade. If our hypothesis is confirmed, we will have identified a novel way to reduce the thrombogenicity of oxygenators in ECMO by adjusting the pump-oxygenator distance based on our finding regarding vWF refolding kinetics.

• DFG Programme: Research Grants