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Multimodal Characterization of Flow-Induced Thrombus Initiation and Growth in Extracorporeal Membrane Oxygenation
KTH, School of Engineering Sciences (SCI), Engineering Mechanics, Fluid Mechanics. (FLOW)ORCID iD: 0000-0001-9503-9300
Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607 Hamburg, Germany; Advanced Light Source, Lawrence Berkeley National Laboratory, 6 Cyclotron Rd, Berkeley, CA 94720, USA.ORCID iD: 0000-0002-5772-8065
Umeå Centre for Electron Microscopy, Umeå University, Umeå, Sweden; Science for Life Laboratory, Department of Chemistry, Umeå University, Umeå, Sweden.ORCID iD: 0000-0003-1615-0583
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fiberprocesser. Deutsches Elektronen-Synchrotron DESY, Notkestr. 85, 22607 Hamburg, Germany; Dept. of Fibre and Polymer Technology, KTH, Stockholm, Sweden.ORCID iD: 0000-0002-6940-6012
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

In cases of severe cardiopulmonary failure, extracorporeal membrane oxygenation (ECMO) may be temporarily used as a life-saving support for cardiac and/or lung function. Operating under non-physiological flow conditions, characterized by elevated shear rates and stagnant flow zones, there is an increased risk of inducing thrombosis, bleeding and hemolysis. Pinpointing the underlying mechanism triggering the onset of thrombus formation may aid development of device design, as well as management of anti-coagulation, benefiting patient outcome. Here we present a combined methodology enabling a multiscale understanding of thrombus development. Two thrombi collected from different ECMO circuits were analyzed by computational fluid dynamics (CFD), ultra small angle X-ray Scattering (USAXS) and scanning electron microscopy (SEM). USAXS quantified the density and bulk alignment of fibrin, building the thrombus scaffold structure. SEM provided information on cellular morphology and surface fibrin structure, and CFD identified regions in the ECMO circuit with high thrombotic potential. Together, this combined approach was able to link local flow conditions and the structural growth of thrombi in ECMO circuits.

National Category
Fluid Mechanics Other Medical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-371647OAI: oai:DiVA.org:kth-371647DiVA, id: diva2:2006443
Funder
Swedish Research Council, 2019-04800
Note

QC 20251016

Available from: 2025-10-14 Created: 2025-10-14 Last updated: 2025-10-16Bibliographically approved
In thesis
1. Flow Dynamics and Thrombus Formation in Extracorporeal Membrane Oxygenation: A Combined Computational and Experimental Study
Open this publication in new window or tab >>Flow Dynamics and Thrombus Formation in Extracorporeal Membrane Oxygenation: A Combined Computational and Experimental Study
2025 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In cases of severe cardiac and/or respiratory failure, extracorporeal membrane oxygenation (ECMO) can be used as a bridge to organ recovery or transplantation. In ECMO, blood is drained through a venous drainage cannula by a pump, pushed through a membrane lung for gas exchange, and returned to the patient through a return cannula. Along this path blood passes through tubing and several connectors. These components expose blood components to elevated shear rates, highly unsteady flow fields, prolonged residence times, and artificial surfaces, increasing the risk of hemolysis, bleeding, and thrombosis.

  This work investigates the flow structures and stresses that arise in ECMO circuit components and connects them to mechanisms for blood damage. It also provides a methodology where the thrombus morphology and composition can be assessed with scanning electron microscopy (SEM) and ultra small angle X-ray scattering (USAXS) to the local flow field. By using large eddy simulations (LES) complemented by Reynolds averaged Navier Stokes (RANS) modeling, flow phenomena were evaluated under clinically relevant operating conditions and compared with experimental observations. Results revealed that the size and intensity of recirculation zones and other flow structures were highly dependent on operating conditions, with inlet recirculation and larger rotating flow cells blocking the main flow at low inlet flow rates in the DP3 pump (Xenios AG,Heilbronn, Germany). The low-weight DP3 impeller exhibited wobbling, that could potentially increase both hemolysis and plastic spallation. Cavities and protrusions were found to promote stagnation, shear layers, with recirculation volumes growing with increased flow rates. Shear rate analysis further identified elongational shear in several locations, including the pump inlet, blade wakes and pump outlet. These regions pose a risk for von Willebrand factor (vWf) unfolding followed by platelet activation and consequently thrombus growth.

Overall, the findings emphasized that both operational settings and circuit design strongly influenced the formation of damaging flow conditions in the ECMO circuit. Linking flow features to thrombus morphology and known mechanisms for blood damage provides a foundation for improved models for thrombosis, refined clinical guidelines, and helps with future device design.

Abstract [sv]

Vid kraftigt nedsatt hjärt- och/eller lungfunktion kan extracorporal membranoxygenering (ECMO) användas i väntan på att organen återhämtar sig eller tills dess att transplantation kan utföras. I ECMO dras blodet ut genom en venös dränagekanyl med hjälp av en pump som sedan trycker blodet genom en membranlunga för gasutbyte. Därefter återförs det syresatta blodet till patienten via en returkanyl. På vägen genom systemet passerar blodet också slangar och ett flertal konnektorer. Dessa komponenter utsätter blodet för höga skjuvkrafter, kraftigt instabila flöden, artificiella ytskikt och risk för att blodkomponenter fastnar i flödesstrukturerna under en längre tid vilket kan leda till både hemolys, blödning och trombos.

Det här arbetet utvärderar flödesstrukturer och skjuvkrafter som uppstår i ECMO systemets komponenter och kopplar dem till mekanismer för skador på blodets beståndsdelar. Arbetet ger också förslag på en metod för att utvärdera trombers morfologi och komposition med svepelektronmikroskopi och småvinkelspridning av röntgenstrålar (small angle X-ray scattering) och kopplar det till det lokala flödesfältet. Genom att använda large eddy simulations (LES) och Reynolds averaged Navier Stokes (RANS) modellering kunde olika flödesfenomen utvärderas med kliniskt relevanta testvillkor och jämföras med experimentella observationer. Resultaten visade att storlek och intensitet hos recirkulationszoner och andra flödesstrukturer var beroende av testvillkoren, där kraftigare inloppsrecirkulation och större roterande flödesceller blockerade flödet. Detta var särskilt tydligt vid lägre inloppsflöden i DP3-pumpen. Den lätta impellern hos DP3-pumpen konstaterades wobbla, något som kan ge upphov till både hemolys och utfällning av mikroplaster. Hålrum och utbuktande delar påvisades ge upphov till flödesstagnation, skjuvlager och recirkulationsvolymer vilka växte med ökad flödeshastighet. Genom att undersöka skjuvhastigheter kunde regioner med elongerande skjuvegenskaper konstateras i pumpinloppet, bladvakerna och pumputloppet. I dessa regioner är risken större för att von Willebrandfaktorn (vWf) ska rullas ut och aktivera blodplättarna runt sig vilket följaktligen kan leda till trombos.

Sammanfattningsvis visar resultaten att testvillkor och komponentdesign hos ECMO-komponenter kraftigt påverkar skapandet av flödesvillkor, vilka kan skada och aktivera blodkomponenter. Genom att koppla flödesstrukturer till trombmorfologin och mekanismer som är kända för att skada blodkomponenter skapas i detta arbetet en grund för bättre trombosmodeller, tydligare kliniska riktlinjer och hjälp för framtida komponentdesign.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2025
Series
TRITA-SCI-FOU ; 2025:45
Keywords
extracorporeal membrane oxygenation, large eddy simulations, blood flow characteristics, thrombosis, von Willebrand factor, small angle X-ray scattering, scanning electron microscopy
National Category
Fluid Mechanics Other Medical Engineering
Research subject
Engineering Mechanics
Identifiers
urn:nbn:se:kth:diva-371662 (URN)978-91-8106-389-9 (ISBN)
Public defence
2025-10-30, F3, Lindstedtsvägen 26, Stockholm, 10:00 (English)
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Supervisors
Note

QC 251015

Available from: 2025-10-15 Created: 2025-10-15 Last updated: 2025-11-24Bibliographically approved

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Nilsson, FridaRoth, Stephan V.Prahl Wittberg, Lisa

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