Abstract Number: OC 31.3
Meeting: ISTH 2021 Congress
Background: The MYH9 gene encodes for the heavy chain of non-muscle myosin IIA (NMMHC-IIA), which is involved in various cellular processes that require contractile force generation. Although cytoskeleton’s role in platelet function is well known, the consequences of mutations in the MYH9 gene on NMMHC-IIA dependent intrinsic biomechanics of platelets are only poorly understood.
Aims: Analysis of biomechanical properties of platelets from patients with MYH9-related disorders.
Methods: We analyzed the biomechanical properties of platelets from MYH9-RD patients with a point mutation in the MYH9 gene at positions 1424 and 1841 located in the rod domain. High-throughput real-time fluorescence and deformability cytometry (RT-FDC) was used to assess the deformability of single platelets. F-actin content of platelets was determined by Phalloidin-Atto 647 binding in flow cytometry. Elastic and viscoelastic properties of platelet aggregates formed under hydrodynamic shear on the collagen matrix were quantified by the microcolloidal probe spectroscopy.
Results: Platelets from MYH9-RD patients showed up to two-fold lower deformation (i.e. stiffer platelets) and were larger in size (p.D1424N: deformation 0.051 ± 0.024 (mean ± SD), size 10.26 µm2 ± 0.91 (mean ± CD) and p.E1841K: deformation 0.06 ± 0.011, size 6.4 µm2 ± 0.88) than control platelets from healthy individual (deformation 0.151 ± 0.033, size 4.10 µm2 ± 0.24). Basal F-actin content was two-fold higher in platelets from than in the control platelets. Under shear on collagen, from MYH9-RD patients formed all thrombi, which were biomechanically softer (p.D1424N: Young’s modulus E: 1.06 kPa ± 0.75 (mean ± SD) and p.E1841K Young’s modulus E: 1.97 kPa ± 0.94) than thrombi from healthy individuals (Young’s modulus E: 2.37 kPa ± 1.544).
Conclusions: We demonstrate that single platelets from MYH9-RD patients with the point mutation in the MYH9 gene (p.D1424N and p.E1841K) are biomechanically stiffer with higher F-actin content than those from healthy individuals, but single thrombi from MYH9-RD patients are softer than thrombi from healthy individuals.
To cite this abstract in AMA style:Sachs L, Baumann J, Wesche J, Nestler P, Zaninetti C, Greinacher A, Bender M, Otto O, Palankar R. Platelets from Patients with MYH9 Related Disorders Are Mechanically Stiffer [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/platelets-from-patients-with-myh9-related-disorders-are-mechanically-stiffer/. Accessed August 8, 2022.
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