TY - JOUR
T1 - A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions
AU - Petkantchin, R.
AU - Rousseau, A.
AU - Eker, O.
AU - Zouaoui Boudjeltia, K.
AU - Raynaud, F.
AU - Chopard, B.
AU - INSIST investigators
AU - Hoekstra, A.
AU - Padmos, R.
AU - Azizi, V.
AU - Miller, C.
AU - van der Kolk, M.
AU - Majoie, Charles
AU - van Bavel, Ed
AU - Marquering, Henk
AU - Arrarte-Terreros, Nerea
AU - Konduri, Praneeta
AU - Georgakopoulou, Sissy
AU - Roos, Yvo
AU - van der Lugt, Aad
AU - Dippel, Diederik W. J.
AU - Lingsma, Hester L.
AU - Boodt, Nikki
AU - Samuels, Noor
AU - Payne, Stephen
AU - Jozsa, Tamas
AU - el-Bouri, Wahbi K.
AU - Gilvarry, Michael
AU - McCarthy, Ray
AU - Duffy, Sharon
AU - Dwivedi, Anushree
AU - Fereidoonnezhad, Behrooz
AU - Moerman, Kevin
AU - McGarry, Patrick
AU - Staessens, Senna
AU - de Meyer, Simon
AU - Vandelanotte, Sarah
AU - Migliavacca, Francesco
AU - Dubini, Gabriele
AU - Luraghi, Giulia
AU - Rodriguez Matas, Jose Felix
AU - Bridio, Sara
AU - Blanc-Guillemaud, Vanessa
AU - Panteleev, Mikhail
AU - Shibeko, Alexey
N1 - With supplementary information. - Author correction published in: Scientific Reports (2023) 13:20369.
PY - 2023/8/22
Y1 - 2023/8/22
N2 - One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.
AB - One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.
UR - https://doi.org/10.1038/s41598-023-47162-0
UR - http://www.scopus.com/inward/record.url?scp=85168711950&partnerID=8YFLogxK
UR - https://pure.uva.nl/ws/files/162829554/41598_2023_40973_MOESM1_ESM.pdf
U2 - 10.1038/s41598-023-40973-1
DO - 10.1038/s41598-023-40973-1
M3 - Article
C2 - 37608073
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 13681
ER -