@article{Annabelle Dupont_Christelle Soukaseum_Mathilde Cheptou_Frédéric Adam_Thomas Nipoti_Marc-Damien Lourenco-Rodrigues_Paulette Legendre_Valérie Proulle_Antoine Rauch_Charlotte Kawecki_Marijke Bryckaert_Jean-Philippe Rosa_Camille Paris_Catherine Ternisien_Pierre Boisseau_Jenny Goudemand_Delphine Borgel_Dominique Lasne_Pascal Maurice_Peter J. Lenting_Cécile V. Denis_Sophie Susen_Alexandre Kauskot_2019, place={Pavia, Italy}, title={Relevance of platelet desialylation and thrombocytopenia in type 2B von Willebrand disease: preclinical and clinical evidence}, volume={104}, url={https://haematologica.org/article/view/9172}, DOI={10.3324/haematol.2018.206250}, abstractNote={Patients with type 2B von Willebrand disease (vWD) (caused by gain-of-function mutations in the gene coding for von Willebrand factor) display bleeding to a variable extent and, in some cases, thrombocytopenia. There are several underlying causes of thrombocytopenia in type 2B vWD. It was recently suggested that desialylation-mediated platelet clearance leads to thrombocytopenia in this disease. However, this hypothesis has not been tested <em>in vivo</em>. The relationship between platelet desialylation and the platelet count was probed in 36 patients with type 2B von Willebrand disease (p.R1306Q, p.R1341Q, and p.V1316M mutations) and in a mouse model carrying the severe p.V1316M mutation (the 2B mouse). We observed abnormally high elevated levels of platelet desialylation in both patients with the p.V1316M mutation and the 2B mice. <em>In vitro</em>, we demonstrated that 2B p.V1316M/von Willebrand factor induced more desialylation of normal platelets than wild-type von Willebrand factor did. Furthermore, we found that N-glycans were desialylated and we identified αIIb and β3 as desialylation targets. Treatment of 2B mice with sialidase inhibitors (which correct platelet desialylation) was not associated with the recovery of a normal platelet count. Lastly, we demonstrated that a critical platelet desialylation threshold (not achieved in either 2B patients or 2B mice) was required to induce thrombocytopenia <em>in vivo</em&gt;. In conclusion, in type 2B vWD, platelet desialylation has a minor role and is not sufficient to mediate thrombocytopenia.}, number={12}, journal={Haematologica}, author={Annabelle Dupont and Christelle Soukaseum and Mathilde Cheptou and Frédéric Adam and Thomas Nipoti and Marc-Damien Lourenco-Rodrigues and Paulette Legendre and Valérie Proulle and Antoine Rauch and Charlotte Kawecki and Marijke Bryckaert and Jean-Philippe Rosa and Camille Paris and Catherine Ternisien and Pierre Boisseau and Jenny Goudemand and Delphine Borgel and Dominique Lasne and Pascal Maurice and Peter J. Lenting and Cécile V. Denis and Sophie Susen and Alexandre Kauskot}, year={2019}, month={Dec.}, pages={2493-2500} }