Abstract Number: PB1376
Meeting: ISTH 2020 Congress
Background: Immune thrombocytopenia (ITP) is a bleeding disorder due to multiple alterations of the immune system leading to low platelet count and bleeding. Thus, these data suggests that targeting desialylation might be potential approach to modulate bleeding tendency.
Aims: To preclinically verify the efficacy of sialidase inhibition on the clinical outcome in ITP, we aimed to establish a humanized mouse model to study and investigate antibody -mediated desialylation of human PLTs, with a focus on bleeding.
Methods: An antibody against murine CD42b was injected into NOD/SCID mice to depleted murine PLTs. After 24 hours, the % of circulating murine PLTs was determined by flow cytometry (FC) and human PLTs were injected in the tail vain with or without pre-incubation with a sialidase. The survival of human PLTs was then determined by FC. The site of PLT destruction was investigated by collecting cells from explanted lung, liver and spleen. Human PLTs in these organs were detected using a novel FC method.
Results: A drastic reduction of the murine PLTs in the mouse circulation (>95%) was observed after injection of CD42b antibody without affecting animal survival. Next, the human PLTs were injected in the mouse tail vein. To investigate the impact of desialylation on PLT clearance, 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±standard error mean (SEM): 28±5%, p value 0.019). Desialylated PLTs were mainly found in the liver. 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 that the use of a humanized mouse model is a useful experimental approaches to investigate PLT-related bleeding diseases.
To cite this abstract in AMA style:Pelzl L, Marini I, Zlamal J, Althaus K, Bakchoul T. Investigations of the Impact of Sialidase-mediated Changes on the Life Span of Human Platelets Using a Humanized in vivo Mouse Model [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/investigations-of-the-impact-of-sialidase-mediated-changes-on-the-life-span-of-human-platelets-using-a-humanized-in-vivo-mouse-model/. Accessed September 21, 2023.
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