Recommendations for defining disturbed flow as laminar, transitional, or turbulent in assays of hemostasis and thrombosis: communication from the ISTH SSC Subcommittee on Biorheology.
Bark, David L; Vital, Eudorah F; Oury, Cécileet al.
2025 • In Journal of Thrombosis and Haemostasis, 23 (1), p. 345 - 358
[en] Blood flow is vital to life, yet disturbed flow has been linked to atherosclerosis, thrombosis, and endothelial dysfunction. The commonly used hemodynamic descriptor "disturbed flow" found in disease and medical devices is not clearly defined in many studies. However, the specific flow regime-laminar, transitional, or turbulent-can have very different effects on hemostasis, thrombosis, and vascular health. Therefore, it remains important to clinically identify turbulence in cardiovascular flow and to have available assays that can be used to study effects of turbulence. The objective of the current communication was to 1) provide clarity and guidance for how to clinically identify turbulence, 2) define standard measures of turbulence that can allow the recreation of flow conditions in a benchtop assay, and 3) review how cells and proteins in the blood can be impacted by turbulence based on current literature.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Bark, David L; Department of Pediatrics, Division of Hematology and Oncology, Washington University in St. Louis, St. Louis, Missouri, USA. Electronic address: bark@wustl.edu
Vital, Eudorah F; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia, USA
Oury, Cécile ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Lam, Wilbur A; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, Georgia, USA, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
Gardiner, Elizabeth E; Division of Genome Science and Cancer, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
Language :
English
Title :
Recommendations for defining disturbed flow as laminar, transitional, or turbulent in assays of hemostasis and thrombosis: communication from the ISTH SSC Subcommittee on Biorheology.
National Institute of Biomedical Imaging and Bioengineering NHMRC - National Health and Medical Research Council NIH - National Institutes of Health NHLBI - National Heart Lung and Blood Institute
Funding text :
Funding information D.L.B. acknowledges funding support from National Institutes of Health; National Heart, Lung, and Blood Institute (R01HL164424); and National Institute of Biomedical Imaging and Bioengineering (R21EB034579). E.E.G. receives funding from the National Health and Medical Research Council of Australia.
Bortot, M., Ashworth, K., Sharifi, A., Walker, F., Crawford, N.C., Neeves, K.B., Bark, Jr D., Di Paola, J., Turbulent flow promotes cleavage of VWF (von Willebrand factor) by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13). Arterioscler Thromb Vasc Biol 39 (2019), 1831–1842.
Stein, P.D., Sabbah, H.N., Turbulent blood flow in the ascending aorta of humans with normal and diseased aortic valves. Circ Res 39 (1976), 58–65.
Becker, R.C., Eisenberg, P., Turpie, A.G., Pathobiologic features and prevention of thrombotic complications associated with prosthetic heart valves: fundamental principles and the contribution of platelets and thrombin. Am Heart J 141 (2001), 1025–1037.
Nesbitt, W.S., Westein, E., Tovar-Lopez, F.J., Tolouei, E., Mitchell, A., Fu, J., Carberry, J., Fouras, A., Jackson, S.P., A shear gradient–dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15 (2009), 665–673.
Moody, L.F., Friction factors for pipe flow. Trans ASME 66 (1944), 671–678.
Bharadvaj, B.K., Mabon, R.F., Giddens, D.P., Steady flow in a model of the human carotid bifurcation. Part I—flow visualization. J Biomech 15 (1982), 349–362.
Taylor, G.I., Experiments with rotating fluids. Proc R Soc Lond A Math Phys Sci 100 (1921), 114–121.
Morshed, K.N., Bark, Jr D., Forleo, M., Dasi, L.P., Theory to predict shear stress on cells in turbulent blood flow. PLoS One, 9, 2014, e105357, 10.1371/journal.pone.0105357.
Zhou, Y., Schroeder, C.M., Single polymer dynamics under large amplitude oscillatory extension. Phys Rev Fluids, 1, 2016, 053301, 10.1103/PhysRevFluids.1.053301.
Sharifi, A., Bark, D., Mechanical forces impacting cleavage of von Willebrand factor in laminar and turbulent blood flow. Fluids, 6, 2021, 67, 10.3390/fluids6020067.
Kuethe, D.O., Measuring distributions of diffusivity in turbulent fluids with magnetic-resonance imaging. Phys Rev A Gen Phys 40 (1989), 4542–4551.
Kuethe, D.O., Gao, J.H., NMR signal loss from turbulence: models of time dependence compared with data. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 51 (1995), 3252–3262.
Dyverfeldt, P., Sigfridsson, A., Kvitting, J.P.E., Ebbers, T., Quantification of intravoxel velocity standard deviation and turbulence intensity by generalizing phase-contrast MRI. Magn Reson Med 56 (2006), 850–858.
De Gennes, P.G., Theory of spin echoes in a turbulent fluid. Phys Lett A 29 (1969), 20–21.
Elkins, C.J., Alley, M.T., Saetran, L., Eaton, J.K., Three-dimensional magnetic resonance velocimetry measurements of turbulence quantities in complex flow. Exp Fluids 46 (2009), 285–296.
Dyverfeldt, P., Gårdhagen, R., Sigfridsson, A., Karlsson, M., Ebbers, T., On MRI turbulence quantification. Magn Reson Imaging 27 (2009), 913–922.
Nygaard, H., Paulsen, P.K., Hasenkam, J.M., Pedersen, E.M., Rovsing, P.E., Turbulent stresses downstream of three mechanical aortic valve prostheses in human beings. J Thorac Cardiovasc Surg 107 (1994), 438–446.
Isaaz, K., Bruntz, J.F., Da Costa, A., Winninger, D., Cerisier, A., de Chillou, C., Sadoul, N., Lamaud, M., Ethevenot, G., Aliot, E., Noninvasive quantitation of blood flow turbulence in patients with aortic valve disease using online digital computer analysis of Doppler velocity data. J Am Soc Echocardiogr 16 (2003), 965–974.
Liu, J.S., Lu, P.C., Chu, S.H., Turbulence characteristics downstream of bileaflet aortic valve prostheses. J Biomech Eng 122 (2000), 118–124.
Le, T.B., Sotiropoulos, F., On the three-dimensional vortical structure of early diastolic flow in a patient-specific left ventricle. Eur J Mech B Fluids 35 (2012), 20–24.
Chnafa, C., Mendez, S., Nicoud, F., Image-based large-eddy simulation in a realistic left heart. Comput Fluids 94 (2014), 173–187.
Domenichini, F., Pedrizzetti, G., Baccani, B., Three-dimensional filling flow into a model left ventricle. J Fluid Mech 539 (2005), 179–198.
Chnafa, C., Mendez, S., Nicoud, F., Image-based simulations show important flow fluctuations in a normal left ventricle: what could be the implications?. Ann Biomed Eng 44 (2016), 3346–3358.
Gülan, U., Rossi, V.A., Gotschy, A., Saguner, A.M., Manka, R., Brunckhorst, C.B., Duru, F., Schmied, C.M., Niederseer, D., A comparative study on the analysis of hemodynamics in the athlete's heart. Sci Rep, 12, 2022, 16666, 10.1038/s41598-022-20839-8.
Gülan, U., Saguner, A.M., Akdis, D., Gotschy, A., Tanner, F.C., Kozerke, S., Manka, R., Brunckhorst, C., Holzner, M., Duru, F., Hemodynamic changes in the right ventricle induced by variations of cardiac output: a possible mechanism for arrhythmia occurrence in the outflow tract. Sci Rep, 9, 2019, 100, 10.1038/s41598-018-36614-7.
Saikrishnan, N., Yap, C.H., Milligan, N.C., Vasilyev, N.V., Yoganathan, A.P., In vitro characterization of bicuspid aortic valve hemodynamics using particle image velocimetry. Ann Biomed Eng 40 (2012), 1760–1775.
Ha, H., Ziegler, M., Welander, M., Bjarnegård, N., Carlhäll, C.J., Lindenberger, M., Länne, T., Ebbers, T., Dyverfeldt, P., Age-related vascular changes affect turbulence in aortic blood flow. Front Physiol, 9, 2018, 36, 10.3389/fphys.2018.00036.
Yamaguchi, T., Kikkawa, S., Yoshikawa, T., Tanishita, K., Sugawara, M., Measurement of turbulence intensity in the center of the canine ascending aorta with a hot-film anemometer. J Biomech Eng 105 (1983), 177–187.
Valen-Sendstad, K., Piccinelli, M., Steinman, D.A., High-resolution computational fluid dynamics detects flow instabilities in the carotid siphon: implications for aneurysm initiation and rupture?. J Biomech 47 (2014), 3210–3216.
Buchmann, N.A., Atkinson, C., Jeremy, M.C., Soria, J., Tomographic particle image velocimetry investigation of the flow in a modeled human carotid artery bifurcation. Exp Fluids 50 (2011), 1131–1151.
Dyverfeldt, P., Hope, M.D., Tseng, E.E., Saloner, D., Magnetic resonance measurement of turbulent kinetic energy for the estimation of irreversible pressure loss in aortic stenosis. JACC Cardiovasc Imaging 6 (2013), 64–71.
Binter, C., Gotschy, A., Sündermann, S.H., Frank, M., Tanner, F.C., Lüscher, T.F., Manka, R., Kozerke, S., Turbulent kinetic energy assessed by multipoint 4-dimensional flow magnetic resonance imaging provides additional information relative to echocardiography for the determination of aortic stenosis severity. Circ Cardiovasc Imaging, 10, 2017, e005486, 10.1161/CIRCIMAGING.116.005486.
Ha, H., Kim, G.B., Kweon, J., Huh, H.K., Lee, S.J., Koo, H.J., Kang, J.W., Lim, T.H., Kim, D.H., Kim, Y.H., Kim, N., Yang, D.H., Turbulent kinetic energy measurement using phase contrast MRI for estimating the post-stenotic pressure drop: in vitro validation and clinical application. PLoS One, 11, 2016, e0151540, 10.1371/journal.pone.0151540.
Dyverfeldt, P., Kvitting, J.P.E., Sigfridsson, A., Engvall, J., Bolger, A.F., Ebbers, T., Assessment of fluctuating velocities in disturbed cardiovascular blood flow: in vivo feasibility of generalized phase-contrast MRI. J Magn Reson Imaging 28 (2008), 655–663.
Lantz, J., Ebbers, T., Engvall, J., Karlsson, M., Numerical and experimental assessment of turbulent kinetic energy in an aortic coarctation. J Biomech 46 (2013), 1851–1858.
Andersson, M., Karlsson, M., Characterization of anisotropic turbulence behavior in pulsatile blood flow. Biomech Model Mechanobiol 20 (2021), 491–506.
Arzani, A., Dyverfeldt, P., Ebbers, T., Shadden, S.C., In vivo validation of numerical prediction for turbulence intensity in an aortic coarctation. Ann Biomed Eng 40 (2012), 860–870.
Lee, S.E., Lee, S.W., Fischer, P.F., Bassiouny, H.S., Loth, F., Direct numerical simulation of transitional flow in a stenosed carotid bifurcation. J Biomech 41 (2008), 2551–2561.
Ziegler, M., Alfraeus, J., Good, E., Engvall, J., De Muinck, E., Dyverfeldt, P., Exploring the relationships between hemodynamic stresses in the carotid arteries. Front Cardiovasc Med, 7, 2021, 617755, 10.3389/fcvm.2020.617755.
Freidoonimehr, N., Arjomandi, M., Sedaghatizadeh, N., Chin, R., Zander, A., Transitional turbulent flow in a stenosed coronary artery with a physiological pulsatile flow. Int J Numer Method Biomed Eng, 36, 2020, e3347, 10.1002/cnm.3347.
Peterson, S.D., Plesniak, M.W., The influence of inlet velocity profile and secondary flow on pulsatile flow in a model artery with stenosis. J Fluid Mech 616 (2008), 263–301.
Zajac, J., Eriksson, J., Dyverfeldt, P., Bolger, A.F., Ebbers, T., Carlhäll, C.J., Turbulent kinetic energy in normal and myopathic left ventricles. J Magn Reson Imaging 41 (2015), 1021–1029.
Kronborg, J., Svelander, F., Eriksson-Lidbrink, S., Lindström, L., Homs-Pons, C., Lucor, D., Hoffman, J., Computational analysis of flow structures in turbulent ventricular blood flow associated with mitral valve intervention. Front Physiol, 13, 2022, 806534, 10.3389/fphys.2022.806534.
Sabbah, H.N., Walburn, F.J., Stein, P.D., Patterns of flow in the left coronary artery. J Biomech Eng 106 (1984), 272–279.
Mahalingam, A., Gawandalkar, U.U., Kini, G., Buradi, A., Araki, T., Ikeda, N., Nicolaides, A., Laird, J.R., Saba, L., Suri, J.S., Numerical analysis of the effect of turbulence transition on the hemodynamic parameters in human coronary arteries. Cardiovasc Diagn Ther 6 (2016), 208–220.
Young, D.F., Tsai, F.Y., Flow characteristics in models of arterial stenoses. II. Unsteady flow. J Biomech 6 (1973), 547–559.
Young, D.F., Tsai, F.Y., Flow characteristics in models of arterial stenoses. I. Steady flow. J Biomech 6 (1973), 395–410.
Bark, Jr DL., Ku, D.N., Wall shear over high degree stenoses pertinent to atherothrombosis. J Biomech 43 (2010), 2970–2977.
Wiegmann, L., Thamsen, B., De Zélicourt, D., Granegger, M., Boës, S., Schmid Daners, M., Meboldt, M., Kurtcuoglu, V., Fluid dynamics in the HeartMate 3: influence of the artificial pulse feature and residual cardiac pulsation. Artif Organs 43 (2019), 363–376.
Thamsen, B., Gülan, U., Wiegmann, L., Loosli, C., Schmid Daners, M., Kurtcuoglu, V., Holzner, M., Meboldt, M., Assessment of the flow field in the HeartMate 3 using three-dimensional particle tracking velocimetry and comparison to computational fluid dynamics. ASAIO J 66 (2020), 173–182.
Thamsen, B., Blümel, B., Schaller, J., Paschereit, C.O., Affeld, K., Goubergrits, L., Kertzscher, U., Numerical analysis of blood damage potential of the HeartMate II and HeartWare HVAD rotary blood pumps. Artif Organs 39 (2015), 651–659.
Leo, H.L., He, Z., Ellis, J.T., Yoganathan, A.P., Microflow fields in the hinge region of the CarboMedics bileaflet mechanical heart valve design. J Thorac Cardiovasc Surg 124 (2002), 561–574.
Hatoum, H., Maureira, P., Dasi, L.P., A turbulence in vitro assessment of On-X and St Jude Medical prostheses. J Thorac Cardiovasc Surg 159 (2020), 88–97.
Hatoum, H., Yousefi, A., Lilly, S., Maureira, P., Crestanello, J., Dasi, L.P., An in vitro evaluation of turbulence after transcatheter aortic valve implantation. J Thorac Cardiovasc Surg 156 (2018), 1837–1848.
Yoganathan, A.P., Chandran, K., Sotiropoulos, F., Flow in prosthetic heart valves: state-of-the-art and future directions. Ann Biomed Eng 33 (2005), 1689–1694.
Li, C.P., Chen, S.F., Lo, C.W., Lu, P.C., Turbulence characteristics downstream of a new trileaflet mechanical heart valve. ASAIO J 57 (2011), 188–196.
Dasi, L.P., Ge, L., Simon, H.A., Sotiropoulos, F., Yoganathan, A.P., Vorticity dynamics of a bileaflet mechanical heart valve in an axisymmetric aorta. Phys Fluids, 19, 2007, 067105, 10.1063/1.2743261.
Kameneva, M.V., Burgreen, G.W., Kono, K., Repko, B., Antaki, J.F., Umezu, M., Effects of turbulent stresses upon mechanical hemolysis: experimental and computational analysis. ASAIO J 50 (2004), 418–423.
Davies, P.F., Remuzzi, A., Gordon, E.J., Dewey, Jr CF., Gimbrone, Jr MA., Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci U S A 83 (1986), 2114–2117.
Dewey, Jr CF., Bussolari, S.R., Gimbrone, Jr MA., Davies, P.F., The dynamic response of vascular endothelial cells to fluid shear stress. J Biomech Eng 103 (1981), 177–185.
Sallam, A.M., Hwang, N.H., Human red blood cell hemolysis in a turbulent shear flow: contribution of Reynolds shear stresses. Biorheology 21 (1984), 783–797.
Yoganathan, A.P., Woo, Y.R., Sung, H.W., Turbulent shear stress measurements in the vicinity of aortic heart valve prostheses. J Biomech 19 (1986), 433–442.
Meegan, J.E., Bastarache, J.A., Ware, L.B., Toxic effects of cell-free hemoglobin on the microvascular endothelium: implications for pulmonary and nonpulmonary organ dysfunction. Am J Physiol Lung Cell Mol Physiol 321 (2021), L429–L439.
Humphrey, J.D., Schwartz, M.A., Tellides, G., Milewicz, D.M., Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections. Circ Res 116 (2015), 1448–1461.
Stein, P.D., Sabbah, H.N., Measured turbulence and its effect on thrombus formation. Circ Res 35 (1974), 608–614.
Goldsmith, H.L., Marlow, J.C., Flow behavior of erythrocytes. II. Particle motions in concentrated suspensions of ghost cells. J Colloid Interface Sci 71 (1979), 383–407.
Wang, N.H.L., Keller, K.H., Augmented transport of extracellular solutes in concentrated erythrocyte suspensions in Couette flow. J Colloid Interface Sci 103 (1985), 210–225.
Stein, P.D., Sabbah, H.N., Blick, E.F., Contribution of erythrocytes to turbulent blood flow. Biorheology 12 (1975), 293–299.
