Abstract Number: PB0867
Meeting: ISTH 2021 Congress
Background: Immune thrombocytopenia (ITP) is a bleeding disorder due to multiple alterations of the immune system leading to increased platelet (PLT) clearance and bleeding. Murine antibodies against GPIb have been shown to mediate PLT destruction in the liver.
Aims: To establish a humanized mouse model to study and investigate antibody –mediated destruction of human PLTs in vivo and to assess the impact of desialylation on bleeding.
Methods: Murine PLTs were depleted using a monoclonal antibody against CD42b in a NOD/SCID mouse model. After 24 hours, the % of circulating murine PLTs was determined by flow cytometry (FC). Human PLTs were injected in the tail vain with or without pre-incubation with a sialidase and their survival was determined after 1 – 5 hours by FC.
Results: A drastic reduction of the murine PLTs in the mouse circulation (<5%) was observed after injection of CD42b antibody without affecting animal survival. Next, the human PLTs were injected in the mouse blood stream via tail vein and approximately 90% of circulating PLTs were from human origin. To investigate the impact of desialylation on PLT clearance and function, human PLTs were injected upon incubation with sialidase. Interestingly, a fast reduction of the PLT survival compared to control was observed (% human PLT survival after 2 hours, mean±SEM: sialidase incubation vs. buffer: 28±5% vs. 45±3%, p= 0.0191). Higher number of human PLTs were detected after desialylation in the liver compared to the spleen. The bleeding time in the humanized mouse model was tested after murine PLTs depletion. In particular, a significant reduction of the bleeding time was observed after injection of human PLTs upon depletion.
Conclusions: Our finding suggests the use of this mouse model as potential tool for different experimental approaches in order to investigate human platelet disorders.
To cite this abstract in AMA style:Pelzl L, Singh A, Zlamal J, Marini I, Althaus K, Bakchoul T. Investigations of the Impact of Sialidase-mediated Changes on Bleeding Using a Humanized in vivo Mouse Model [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/investigations-of-the-impact-of-sialidase-mediated-changes-on-bleeding-using-a-humanized-in-vivo-mouse-model/. Accessed September 16, 2021.
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