Abstract Number: OC 22.3
Meeting: ISTH 2022 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » VWF and von Willebrand Factor Disorders - Clinical Conditions
Background: Platelet-inspired nanoparticles that emulate platelet’s injury site-specific adhesion and aggregation functions via surface-decoration with three biofunctional peptides (von Willebrand factor (VWF)/phospholipid-binding peptides (VBP), collagen-binding peptides (CBP) and fibrinogen-mimetic peptides (FMP), have shown haemostatic efficiency in pre-clinical models of thrombocytopenia and trauma. Therefore, it was investigated whether such nanoparticles could be beneficial in the treatment of von Willebrand disease (VWD).
Aims: To assess haemostatic efficacy of platelet-inspired nanoparticles in VWF-KO and VWD-type 2B mice following tail-clip injury.
Methods: VWF-KO and VWD-type 2B mice received 2 mg/kg of different nanoparticle formulations: undecorated (control), single, double or triple peptide-decorated (VBP and/or CBP and/or FMP). Ten minutes post-injection, 3 mm of the tail tip was amputated and blood was collected over 20 min for VWF-KO mice and 30 min for VWD-type 2B mice. Quantitative data (mean±SD) were compared with ANOVA and Tukey’s multiple comparisons test.
Results: In VWF-KO mice, triple peptide-decorated particles significantly reduced bleeding compared to control particles (183±174 µL vs 539±203 µL; p < 0.0001) and not statistically different than wild-type mice (19±18 µL; p=0.2043). Here, single or double peptide-decorated particles did not significantly reduce bleeding. In VWD-type 2B mice, bleeding was significantly reduced with triple peptide-decorated particles compared to control particles (631±206 µL vs 966±199 µL, p=0.0001) and with two combinations of double peptide-decorated particles compared to control particles (587±271 µL with CBP+VBP, p=0.0003; 568±286 µL with CBP+FMP, p < 0.0001). Double peptide-decorated particles with VBP+FMP or single peptide-decorated particles did not affect bleeding.
Conclusion(s): Platelet-inspired biosynthetic nanoparticles significantly reduced bleeding in VWD murine models. In VWD-type 2B mice, the importance of the CBP-decoration highlights the pivotal role of collagen in particle anchoring and action. In VWF KO mice, all 3 peptides were required to achieve haemostatic efficiency. These results warrant further investigation of platelet-inspired nanoparticles as a novel strategy for the haemostatic management of VWD.
To cite this abstract in AMA style:
Roullet S, Luc N, Rayes J, Adam F, Ditto A, Gahagan E, Pawlowski C, Bruckman M, Lenting P, Sen Gupta A, Denis C. Effects of platelet-inspired haemostatic nanoparticles on bleeding in von Willebrand disease murine models [abstract]. https://abstracts.isth.org/abstract/effects-of-platelet-inspired-haemostatic-nanoparticles-on-bleeding-in-von-willebrand-disease-murine-models/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/effects-of-platelet-inspired-haemostatic-nanoparticles-on-bleeding-in-von-willebrand-disease-murine-models/