Platelet proteome and function in X-linked thrombocytopenia with thalassemia and < i > in silico < /i > comparisons with gray platelet syndrome.

Platelet proteome and function in X-linked thrombocytopenia with thalassemia and <i>in silico</i> comparisons with gray platelet syndrome. Haematologica. 2020 Sep 28;Online ahead of print: Authors: Bergemalm D, Ramström S, Kardeby C, Hultenby K, Eremo AG, Sihlbom C, Bergström J, Palmblad J, Åström M Abstract In X-linked thrombocytopenia with thalassemia (XLTT; OMIM 314050), caused by the mutation p.R216Q in exon 4 of the GATA1 gene, male hemizygous patients display macrothrombocytopenia, bleeding diathesis and a β-thalassemia trait. Herein, we describe findings in two unrelated Swedish XLTT families with a bleeding tendency exceeding what is expected from the thrombocytopenia. Blood tests revealed low P-PAI-1 and P-factor 5, and elevated S-thrombopoietin levels. Transmission electron microscopy showed diminished numbers of platelet α- and dense granules. The proteomes of isolated blood platelets from 5 male XLTT patients, compared to 5 gender- and age matched controls, were explored. Quantitative mass spectrometry showed alterations of 83 proteins (fold change ≥±1.2, q< .05). Of 46 downregulated proteins, 39 were previously reported to be associated with platelet granules. Reduced protein levels of PTGS1 and SLC35D3 were validated in megakaryocytes of XLTT bone marrow biopsies by immunohistochemistry. Platelet function testing by flow cytometry revealed low dense- and α-granule release and fibrinogen binding ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research