Background: Clot formation on foreign surfaces of extracorporeal membrane oxygenation systems is a frequent event. Herein, we show an approach that mimics the enzymatic process of endogenous nitric oxide (NO) release on the oxygenator membrane via a biomimetic, non-fouling microgel coating to spatiotemporally inhibit the platelet (PLT) activation and improve antithrombotic properties. This study aims to evaluate the potential of this biomimetic coating towards NO-mediated PLT inhibition and thereby the reduction of clot formation under flow conditions. Methods: Microgel-coated (NOrel) or bare (Control) poly(4-methyl pentene) (PMP) fibers were inserted into a test channel and exposed to a short-term continuous flow of human blood. The analysis included high-resolution PLT count, pooled PLT activation via β-Thromboglobulin (β-TG) and the visualization of remnants and clots on the fibers using scanning electron microscopy (SEM). Results: In the Control group, PLT count was significantly decreased, and β-TG concentration was significantly elevated in comparison to the NOrel group. Macroscopic and microscopic visualization showed dense layers of stable clots on the bare PMP fibers, in contrast to minimal deposition of fibrin networks on the coated fibers. Conclusion: Endogenously NO-releasing microgel coating inhibits the PLT activation and reduces the clot formation on PMP fibers under dynamic flow.

Introduction: Due to improved technology and increased application the mortality during extracorporeal membrane oxygenation (ECMO) is constantly declining. Nevertheless, complications including haemorrhage or thrombus formation remain frequent. Local mitigation of coagulation within an ECMO system to prevent thrombus formation on ECMO components and optimizing systemic anticoagulation is an approach to reduce clotting and bleeding complications at once. Foreign surfaces of ECMO systems, activate platelets (PLTs), which besides their major role in coagulation, can trigger the formation of neutrophil extracellular traps (NETs) contributing to robust thrombus formation. The impact of a reduced PLT count on PLT activation and NET formation is of paramount importance and worth investigating. Methods: In this study platelet poor (PLT^–) and native (PLT⁺) heparinized human blood was circulated in two identical in vitro test circuits for ECMO devices for 6 hours. PLT reduction was achieved by a centrifugation protocol prior to the experiments. To achieve native coagulation characteristics within the test circuits, the initial heparin dose was antagonized by continuous protamine administration. Results: The PLT^– group showed significantly lower platelet activation, basal NET formation and limited clot stability measured via thromboelastometry. Fluorescent and scanning electron microscope imaging showed differences in clot composition. Both groups showed equal clot formation within the circuit. Conclusions: This study demonstrated that the reduction of PLTs within an ECMO system is associated with limited PLT activation and NET formation, which reduces clot stability but is not sufficient to inhibit clot formation per se.

Background: Hemocompatibility of left ventricular assist devices is essential for preventing adverse events. In this study, we compared the hemocompatibility of an axial-flow (Sputnik) to a centrifugal-flow (HeartMate 3) pump. Methods: Both pumps were integrated into identical in vitro test circuits, each filled with 75 mL heparinized human blood of the same donor. During each experiment (n = 7), the pumps were operated with equal flow for six hours. Blood sampling and analysis were performed on a regular schedule. The analytes were indicators of hemolysis, coagulation activation, platelet count and activation, as well as extracellular vesicles. Results: Sputnik induced higher hemolysis compared to the HeartMate 3 after 360 min. Furthermore, platelet activation was higher for Sputnik after 120 min onward. In the HeartMate 3 circuit, the platelet count was reduced within the first hour. Furthermore, Sputnik triggered a more pronounced increase in extracellular vesicles, a potential trigger for adverse events in left ventricular assist device application. Activation of coagulation showed a time-dependent increase, with no differences between both groups. Conclusions: This experimental study confirms the hypothesis that axial-flow pumps may induce stronger hemolysis compared to centrifugal pumps, coming along with larger amounts of circulating extracellular vesicles and a stronger PLT activation.

Clot formation inside a membrane oxygenator (MO) due to blood-to-foreign surface interaction represents a frequent complication during extracorporeal membrane oxygenation. Since current standard monitoring methods of coagulation status inside the MO fail to detect clot formation at an early stage, reliable sensors for early clot detection are in demand to reduce associated complications and adverse events. Bioimpedance analysis offers a monitoring concept by integrating sensor fibers into the MO. Herein, the feasibility of clot detection via bioimpedance analysis is evaluated. A custom-made test chamber with integrated titanium fibers acting as sensors was perfused with heparinized human whole blood in an in vitro test circuit until clot formation occurred. The clot detection capability of bioimpedance analysis was directly compared to the pressure difference across the test chamber (ΔP-TC), analogous to the measurement across MOs (ΔP-MO), the clinical gold standard for clot detection. We found that bioimpedance measurement increased significantly 8 min prior to a significant increase in ΔP-TC, indicating fulminant clot formation. Experiments without clot formation resulted in a lack of increase in bioimpedance or ΔP-TC. This study shows that clot detection via bioimpedance analysis under flow conditions in a blood-perfused test chamber is generally feasible, thus paving the way for further investigation.

According to the Extracorporeal Life Support Organization (ELSO) guidelines, pre-assembled and already primed extracorporeal membrane oxygenation (ECMO) systems can be safely stored for up to 30 days under specific conditions. This study gives a detailed overview of existing pre-assembly practices. An anonymous online survey was conducted among chief perfusionists at German ECMO centers. Forty-four of a total of 83 ECMO centers (53%) completed the survey. Thirty-three percent do not preassemble ECMO systems. Seventy-seven percent (n = 34) reported having preassembled ECMO systems readily available (30% dry preassembly/20% wet preassembly/27% wet preassembly with circulation). Half of the participating centers (50%) reported having a standard operating procedure (SOP) and the majority (57%) of chief perfusionists expressed a need for an evidence-based SOP. A maximum storage time for wet preassembled ECMO systems is established in 88% of departments. On average, wet preassembled systems are discarded after 20 days, which is below the ELSO’s safe limit of 30 days. Overall, this survey reveals a heterogeneous approach regarding the practice of provisioning preassembled ECMO systems. The demand for an evidence-based SOP for the preassembly and storing of ECMO systems becomes evident, necessitating the determination of hygienic standards, regular training, and a reliable maximum storage period.

Artificial organs, such as extracorporeal membrane oxygenators, dialyzers, and hemoadsorber cartridges, face persistent challenges related to the flow distribution within the cartridge. This uneven flow distribution leads to clot formation and inefficient mass transfer over the device's functional surface. In this work, a comprehensive methodology is presented for precisely integrating triply periodic minimal surfaces (TPMS) into module housings and question whether the internal surface topology determining the flow distribution affects blood coagulation. Three module types are compared with different internal topologies: tubular, isometric, and anisometric TPMS. First, this study includes a computational fluid dynamics (CFD) simulation of the internal hemodynamics, validated through experimental residence time distributions (RTD). Blood tests using human whole blood and subsequent visualization of blood clots by computed tomography, allow the quantification of structure‐induced blood clotting. The results indicate that TPMS topologies, particularly anisometric ones, serve as effective flow distributors and significantly reduce and delay blood clotting compared to conventional tubular geometries. For these novel TPMS modules, the inner surfaces can be activated chemically or functionalized to function as a selective adsorption site or biocatalytic surface or made of a permeable material to facilitate mass transfer.