Periodic Reporting for period 1 - fitsCAN (Blood flow induced thrombosis and stenosis due to cannulation – an interdisciplinary study)
Berichtszeitraum: 2022-09-01 bis 2025-02-28
In extracorporeal organ support, one or more organ functions are supported via different types of management of the blood outside of the body. Examples of this are intermittent, or continuous renal replacement therapy, and extracorporeal life support (extracorporeal carbon dioxide removal, extracorporeal cardio-pulmonary resuscitation, and extracorporeal membrane oxygenation (ECMO)). The latter are used for temporary lung- and/or heart-failure. About 1.5 million patients require hemodialysis worldwide whereas ECMO has had an essential life-saving role during both the COVID-19 and H1N1 pandemic but could be considered for any kind of refractory respiratory failure when conventional intensive care does not suffice. In both treatments, two or more accesses to the human circulatory system are used; one for blood drainage and another to return oxygenated and/or cleaned blood. The flow velocity in the cannula and the cannulated blood vessels is often significantly higher than physiologically experienced. The high flow rate implies that larger forces (stress) act on the blood cells and the vessel walls that enhance the risk for complications in the form of formation of stenoses and/or thrombi. Both forming of blood clots (thromboembolism) as well as morphological and mechanical changes leading to vessel stenosis are common complications, also influencing treatment efficiency. This project focus on the impact of blood flow on these complications. To connect the onset of thrombus formation or vessel stenosis to the flow dynamics, several different research methodologies, engineering and clinically oriented, need to be applied, synchronized, and carried out in parallel. Clinical data such as medical imaging (computed tomography, CT, and ultrasound, US) are needed to construct laboratory and simulation relevant frameworks. Computational fluid dynamics and fluid mechanical experimental methods are used to assess flow and mixing as well as transport of the different blood components (e.g. blood cells and chemical species). To link the flow to the specific onset of the complications, patient-specific coagulation data is analyzed as well as the response of certain individual human proteins to fluid stresses. This in turn requires a project group consisting of experimental and numerical fluid mechanics expertise as well as clinical specialists in nephrology, intensive care/ECMO, and radiology. The combination of the different tools and close interaction between engineering and medicine will facilitate a considerably better understanding of the underlying pathological processes where the outcome of the research will both enable and facilitate device development and clinical decision-making reducing overall treatment complications.
To create the laboratory and simulation framework, patient specific topographical anatomical data of the venous circulatory system including the right atrium, superior and inferior vena cavae was acquired and averaged models for both experimental and numerical studies have been established. This in combination with generalized and simplified geometries of a cannula in a straight vessel have enabled building of basic understanding with respect to fluid physics of clinically relevant flows addressed in this project. The work highlights the care needed when simulating these flows, providing experimental validation data for a canonical flow, but also the effect on the results depending on the performance of cannula with respect to vessel geometry. Moreover, a platform to understand the effect of the different cannulation strategies and cannula design on fluid stresses and treatment complication risks has been formed for veno-venous (VV) ECMO, and a similar structure is currently formed for arterio-venous fistula flows used in HD. To understand the onset of thrombus formation and link this with the fluid stress characteristics, one aspect of the work has been to collect blood clots from ECMO circuit components. This work has required setting up a highly dedicated team to coordinate all aspects from mixing fixation solutions and deliver them to the clinic, incorporate routines in the clinic to investigate the circuits after usage, ensuring, applying, and finally getting time within large international infrastructure to carry out the measurements to understand the composition of the clots and the onset mechanisms. For atrio-venous fistula used in HD, a similarly highly dedicated team has been formed to follow a patient from the time where the fistula is created to a potential development of vessel pathology, assessing the cannula (needle) positioning and flows used during the treatment. This established interaction with clinical partners and colleagues is key to in ensure a feedback loop between engineering and clinic for direct knowledge transfer. The interaction leads to change of perspectives, where the inter-disciplinary knowledge is incorporated to push both disciplines forward. The strong inter-disciplinary exchange enables identifying and defining new fundamental ideas and solutions that can be directly applied to the treatment of individual patient.
In the analysis of blood clots collected from ECMO circuit components after treatment we have been able to assess the mechanical properties and its relation to clot composition and fibrin orientation within the clot. We have found that the blood clot topology and composition differ as compared to what has been reported regarding blood clots in humans. We now continue with the categorization, combining the analysis with the fluid dynamics of the respective ECMO components and the associated patient coagulation data. This work has the potential to provide novel understanding which may change and adjust the treatment, i.e. ECMO management including anti-coagulation management and operating conditions of the ECMO circuit. Moreover, combined with the detailed knowledge of the flow structures developing in these flows as well as mixing characteristics between cannula flow and native blood flow under treatment relevant conditions. This work will also support further model development of the involved processes important to assess the risk for onset of thrombus and stenosis formation and facilitate improved cannulation techniques, strategies, and new devices for reduced complication risks.