Abstract Number: OC 13.1
Meeting: ISTH 2021 Congress
Background: Different mechanisms such as platelet consumption, heparin-induced or sepsis may account for thrombocytopenia during Extracorporeal Membrane Oxygenation (ECMO). However, shedding of glycoprotein (GP) Ibα has been recently identified as a potential mechanism of platelet clearance. There is also evidence that platelet-GPIbα shedding is sensitive to high shear stress, a rheological condition provided by ECMO.
Aims: To investigate whether a shear-induced platelet-GPIbα shedding could promote thrombocytopenia under ECMO and the potential role of increased VWF-GPIbα interaction as a trigger
Methods: We first investigated in a cohort of 30 ECMO patients the time course of thrombocytopenia and platelet-GPIbα shedding. In an ECMO circulatory loop model, we next assessed the impact of shear stress on i) platelet-GPIbα shedding and ii) the role of VWF-GPIbα interaction on this shedding by inhibiting this interaction. Plasma levels of soluble GPIbα (assessed by ELISA) and GPIbα/GPIX MFI ratio (determined by flow cytometry) were used as surrogate markers of platelet-GPIbα shedding. We further evaluated in a NOD/SCID mouse model the clearance of platelets after their exposure to ECMO rheological conditions.
Results: An increase of plasma soluble GPIbα and a decrease of mean platelet count were both observed 24 hours after ECMO implantation (p=0.005 and p<0.0001, respectively, Fig.1A and 1B). Two days after ECMO removal, platelet count was restored. When perfusing platelets for 180 min in an ECMO loop model, we observed a time and shear dependent increase in platelet-GPIbα shedding (Fig 2A), which occurred independently of VWF-GPIbα interaction. When transfusing those shear-exposed human platelets to NOD/SCID mice, we observed a significant increase of platelets clearance when compared to unsheared-platelets (Fig 2B).
Conclusions: ECMO shear-induced platelet-GPIbα shedding promotes platelets clearance independently from VWF-GPIbα interaction. Inhibiting platelet-GPIbα shedding is a potential approach to reduce thrombocytopenia during ECMO support.
To cite this abstract in AMA style:Rauch A, Dupont A, Rosa M, Casari C, Ruez R, Ung A, Jeanpierre E, Didelot M, Rousse N, J Lenting P, Moussa M, Desvages M, Vincent F, Vincentelli A, Denis C, Van Belle E, Susen S. Shear-induced Platelet-GPIbα Shedding under Extracorporeal Membrane Oxygenation Promotes Thrombocytopenia Independently from von Willebrand Factor [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/shear-induced-platelet-gpib%ce%b1-shedding-under-extracorporeal-membrane-oxygenation-promotes-thrombocytopenia-independently-from-von-willebrand-factor/. Accessed November 29, 2023.
« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/shear-induced-platelet-gpib%ce%b1-shedding-under-extracorporeal-membrane-oxygenation-promotes-thrombocytopenia-independently-from-von-willebrand-factor/