Hemodynamic activation of von Willebrand factor: an experimental study for predicting thrombus formation in blood-contacting medical devices
https://doi.org/10.15825/1995-1191-2026-2-218-226
Abstract
Objective: to evaluate the effect of hemodynamic stress on the functional activity of von Willebrand factor (VWF) in vitro and to assess the potential of these data for predicting thrombus formation during testing of blood-contacting medical devices. Materials and methods. Fresh human platelet-rich plasma (PRP) was used in all experiments. Hemodynamic conditions mimicking vascular stenosis were simulated in a closed-loop system equipped with a peristaltic pump using a narrow channel (diameter 0.7 mm), generating shear rates (γ) of 1000, 3000, and 5000 s–1. Control experiments were performed under low-shear conditions in a wider channel (diameter 3 mm). von Willebrand factor activity (vWF Act, %) was measured after one and two circulation cycles. Results. Under control conditions, the reduction in VWF activity was minimal, decreasing to 69.2% after two circulation cycles. In stenosis-like channels, a pronounced decrease in VWF activity was observed, with the magnitude depending on shear rate: 65.1% at γ = 1000 s–1, 63.6% at γ = 3000 s–1, and 62.6% at γ = 5000 s–1. The most substantial decline occurred after the first passage through the stenotic segment. At the highest shear rate (γ = 5000 s–1), microscopic analysis revealed the formation of platelet aggregates. Conclusion. The study demonstrates that increasing shear rate leads to enhanced activation and proteolytic degradation of VWF, primarily due to the loss of high-molecular-weight multimers. These findings highlight the critical role of hydrodynamic conditions in the development of hemostatic disturbances associated with vascular stenoses and mechanical circulatory support systems. Incorporating the assessment of VWF activity and multimer distribution into testing protocols for vascular prostheses and extracorporeal devices may improve prediction of their hemocompatibility.
About the Authors
D. N. ShilkinRussian Federation
Dmitry N. Shilkin.
135, Rublevskoye Shosse, 121552, Moscow
Phone: (922) 892-28-98
R. R. Salokhedinova
Russian Federation
Moscow
A. S. Buchnev
Russian Federation
Moscow
V. A. Elenkin
Russian Federation
Moscow
References
1. Grudinin NV, Bogdanov VK, Buchnev AS, Esipova OYu. Development of an extracorporeal pump for the ECMO system. Russian Journal of Transplantology and Artificial Organs. 2024; 26 (4): 133–139. https://doi.org/10.15825/1995-1191-2024-4-149-156.
2. Kuleshov AP, Itkin GP, Baybikov AS. Development of a channel-type centrifugal pump. Russian Journal of Transplantology and Artificial Organs. 2018; 20 (3): 32–39. https://doi.org/10.15825/1995-1191-2018-3-32-39.
3. Kuleshov AP, Itkin GP, Buchnev AS, Drobyshev AA. Mathematical evaluation of hemolysis of a channel centrifugal pump. Russian Journal of Transplantology and Artificial Organs. 2020; 22 (3): 79–85. https://doi.org/10.15825/1995-1191-2020-3-79-85.
4. Itkin GP, Dmitrieva OYu, Buchnev AS, Drobyshev AA, Kuleshov AP, Volkova EA et al. Results of experimental studies of the pediatric axial pump «DON-3». Russian Journal of Transplantology and Artificial Organs. 2018; 20 (2): 61–68. https://doi.org/10.15825/1995-1191-2018-2-61-68.
5. Mei X, Lu B, Wu P, Zhang L. In vitro study of red blood cell and VWF damage in mechanical circulatory support devices based on blood-shearing platform. Proc Inst Mech Eng H. 2022 Jun; 236 (6): 860–866. doi: 10.1177/09544119221088420.
6. Naveed A, Naveed B, Khan MA, Asif T. Gastrointestinal bleeding in recipients of left ventricular assist devices – a systematic review. Heart Fail Rev. 2023 Sep; 28 (5): 1163–1175. doi: 10.1007/s10741-023-10313-6.
7. Pham OL, Feher SE, Nguyen QT, Papavassiliou DV. Distribution and history of extensional stresses on vWF surrogate molecules in turbulent flow. Sci Rep. 2022 Jan 7; 12 (1): 171. doi: 10.1038/s41598-021-04034-9.
8. Jahangiri P, Veen KM, van Moort I, Bunge JH, Constantinescu A, Sjatskig J еt al. Early Postoperative Changes in Von Willebrand Factor Activity Are Associated With Future Bleeding and Stroke in HeartMate 3 Patients. ASAIO J. 2025 Jan 1; 71 (1): 27–35. doi: 10.1097/MAT.0000000000002250.
9. Rauch A, Susen S, Zieger B. Acquired von Willebrand Syndrome in Patients With Ventricular Assist Device. Front Med (Lausanne). 2019 Feb 5; 6: 7. doi: 10.3389/fmed.2019.00007.
10. Porter S, Clark IM, Kevorkian L, Edwards DR. The ADAMTS metalloproteinases. Biochem J. 2005 Feb 15; 386 (Pt 1): 15–27. doi: 10.1042/BJ20040424.
11. Waldow HC, Westhoff‑Bleck M, Widera C, Templin C, von Depka M. Acquired von Willebrand syndrome in adult patients with congenital heart disease. Int J Cardiol. 2014 Oct 20; 176 (3): 739–745. doi: 10.1016/j.ij-card.2014.07.104.
12. Truskey GA, Yuan F, Katz DF. Transport Phenomena in Biological Systems. 2nd ed. Pearson/Prentice Hall; 2009. ISBN: 978-0131569881. 888 p.
13. Sakariassen KS, Orning L, Turitto VT. The impact of blood shear rate on arterial thrombus formation. Future Sci OA. 2015 Nov 1; 1 (4): FSO30. doi: 10.4155/fso.15.28.
14. Gogia S, Neelamegham S. Role of fluid shear stress in regulating VWF structure, function and related blood disorders. Biorheology. 2015; 52 (5–6): 319–335. doi: 10.3233/BIR-15061.
15. Chan CHH, Inoue M, Ki KK, Murashige T, Fraser JF, Simmonds MJ еt al. Shear‐dependent platelet aggregation size. Artif Organs. 2020 Dec; 44 (12): 1286–1295. doi: 10.1111/aor.13783.
16. Vincent F, Rauch A, Spillemaeker H, Vincentelli A, Paris C, Rosa M еt al. Real-Time Monitoring of von Willebrand Factor in the Catheterization Laboratory: The Seatbelt of Mini-Invasive Transcatheter Aortic Valve Replacement? JACC Cardiovasc Interv. 2018 Sep 10; 11 (17): 1775–1778. doi: 10.1016/j.jcin.2018.05.047.
17. Bańka P, Wybraniec M, Bochenek T, Gruchlik B, Burchacka A, Swinarew A еt al. Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function. J Clin Med. 2023 Sep 29; 12 (19): 6301. doi: 10.3390/jcm12196301.
18. Dong C, Kania S, Morabito M, Zhang XF, Im W, Oztekin A еt al. A mechano-reactive coarse-grained model of the blood-clotting agent von Willebrand factor. J Chem Phys. 2019 Sep 28; 151 (12): 124905. doi: 10.1063/1.5117154.
19. Shiraishi Y, Tachizaki Y, Inoue Y, Hayakawa M, Yamada A, Kayashima M еt al. Hemolysis and von Willebrand factor degradation in mechanical shuttle shear flow tester. J Artif Organs. 2021 Jun; 24 (2): 111–119. doi: 10.1007/s10047-020-01219-3.
20. Kuleshov AP, Grudinin NV, Buchnev AS, Elenkin VA, Shilkin DN, Bogdanov VK. Evaluation of blood hemolysis during optimization of the ROTAFLOW centrifugal pump impeller. Russian Journal of Transplantology and Artificial Organs. 2025; 27 (3): 117–124. https://doi.org/10.15825/1995-1191-2025-3-117-124.
21. Kuleshov AP, Grudinin NV, Buchnev AS. Optimization of the ROTAFLOW centrifugal pump rotor. Russian Journal of Transplantology and Artificial Organs. 2025; 27 (3): 125–113. https://doi.org/10.15825/1995-1191-2025-3-125-133.
22. Wang Y, Nguyen KT, Ismail E, Donoghue L, Giridharan GA, Sethu P еt al. Effect of pulsatility on shear-induced extensional behavior of Von Willebrand factor. Artif Organs. 2022 May; 46 (5): 887–898. doi: 10.1111/aor.14133.
23. Jhun CS, Xu L, Siedlecki C, Bartoli CR, Yeager E, Lukic B еt al. Kinetic and Dynamic Effects on Degradation of von Willebrand Factor. ASAIO J. 2023 May 1; 69 (5): 467–474. doi: 10.1097/MAT.0000000000001848.
24. Hennessy‑Strahs S, Kang J, Krause E, Dowling RD, Rame JE, Bartoli CR. Patient-specific severity of von Willebrand factor degradation identifies patients with a left ventricular assist device at high risk for bleeding. J Thorac Cardiovasc Surg. 2024 Jan; 167 (1): 196–204. doi: 10.1016/j.jtcvs.2022.03.018.
25. Esipova OYu, Bogdanov VK, Esipov AS, Kuleshov AP, Buchnev AS, Volkova EA et al. Development of a new low-volume oxygenator and creation of a hydrodynamic stand for ex vivo lung perfusion in small animals. Russian Journal of Transplantology and Artificial Organs. 2023; 25 (3): 106–112. https://doi.org/10.15825/1995-1191-2024-3-176-182.
26. Esipova OYu, Buchnev AS, Drobyshev AA, Kuleshov AP, Grudinin NV, Bogdanov VK. Performance Evaluation of Oxygen Transfer of a Small-Sized Membrane Oxygenator. Biomedical Engineering. 2023; 4 (340): 21–25.
27. Itkin GP, Bychnev AS, Kuleshov AP, Drobyshev AA. Haemodynamic evaluation of the new pulsatile-flow generation method in vitro. Int J Artif Organs. 2020 Mar; 43 (3): 157–164. doi: 10.1177/0391398819879939.
28. Buchnev AS, Kuleshov AP, Esipova OYu, Drobyshev AA, Grudinin NV. Hemodynamic evaluation of a pulsating flow generation device in left ventricular assist systems. Russian Journal of Transplantology and Artificial Organs. 2023; 25 (1): 106–112. https://doi.org/10.15825/1995-1191-2019-3-69-75.
29. Pham OL, Feher SE, Nguyen QT, Papavassiliou DV. Computations of the shear stresses distribution experienced by passive particles as they circulate in turbulent flow: A case study for vWF protein molecules. PloS One. 2022; 17 (8): e0273312. doi: 10.1371/journal.pone.0273312.
30. Khairislamov KZ. Techenie Puazeilya dlya zhidkosti s peremennoi vyazkost’yu. Vestnik Yuzhno‑Uralskogo gosudarstvennogo universiteta. Seriya «Matematika. Mekhanika. Fizika». 2013; 5 (2): 170–173.
31. Kazakov LI. Razvitie techeniya Puazeilya v krugloi trube. 2019 Oct 7; (80-V2019); 32.
32. Holmes AP, Ray CJ, Kumar P, Coney AM. A student practical to conceptualize the importance of Poiseuille’s law and flow control in the cardiovascular system. Adv Physiol Educ. 2020 Sep 1; 44 (3): 436–443. doi: 10.1152/advan.00004.2019.
33. Bokeriya LA, Novikova SP. Protezy krovenosnykh sosudov i kardiohirurgicheskie zaplaty s tromboresistentnymi, antimikrobnymi svoistvami i nulevoi khirurgicheskoi poristost’yu. Serdechno‑sosudistye zabolevaniya. Byulleten’ NTsSSKh im. A.N. Bakuleva RAMN. 2008; 9 (4): 5–20.
34. Salokhedinova RR, Novikova SP, Orlova AA, Tsygankov YuM, Sergeev AA, Afanas’eva EA. Otsenka tromboresistentnosti protezov krovenosnykh sosudov s modifitsiruyushchim geparinovym pokrytiem. Serdechno‑sosudistye zabolevaniya. Byulleten’ NTsSSKh im. A.N. Bakuleva RAMN. 2023; 24 (4): 337–346. doi: 10.24022/1810-0694-2023-24-4-337-346.
35. Steiger T, Foltan M, Philipp A, Mueller T, Gruber M, Bredthauer A еt al. Accumulations of von Willebrand factor within ECMO oxygenators: Potential indicator of coagulation abnormalities in critically ill patients? Artif Organs. 2019 Nov; 43 (11): 1065–1076. doi: 10.1111/aor.13513.
36. Liu L, Chen S, Hu D, Zhu Y, Wu C, Liu A еt al. Von Willebrand factor in ECMO: a dynamic modulator of hemorrhage and thrombosis. Shock. 2025 Sep 1; 64 (3): 291–302. doi: 10.1097/SHK.0000000000002632.
37. Van Den Helm S, Letunica N, Barton R, Weaver A, Yaw HP, Karlaftis V еt al. Changes in von Willebrand Factor Multimers, Concentration, and Function During Pediatric Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2023 Apr 1; 24 (4): 268–276. doi: 10.1097/PCC.0000000000003152.
Review
For citations:
Shilkin D.N., Salokhedinova R.R., Buchnev A.S., Elenkin V.A. Hemodynamic activation of von Willebrand factor: an experimental study for predicting thrombus formation in blood-contacting medical devices. Russian Journal of Transplantology and Artificial Organs. 2026;28(2):218-226. (In Russ.) https://doi.org/10.15825/1995-1191-2026-2-218-226
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