Extra bone marrow maturation and repair of erythrocyte membranes

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Genetics of familial forms of thrombocytopenia

The joint application of clinical and genetic investigation to patients with inherited thrombocytopenias, as well as the availability of new methods for studying megakaryopoiesis, has greatly expanded the knowledge of these disorders in the last few years with regard to their etiology, pathogenesis and clinical aspects. In particular, new diseases have been described, as deriving from mutations in the genes FLNA, TUBB1, ITGA2/ITGB3, ANKRD26, CYCS, and ABCG5 or ABCG8. Moreover, forms previously considered separate entities were found to be different clinical aspects of a single disease. For instance, identification of MYH9 as the gene whose mutations cause the May-Hegglin anomaly led to the recognition that Sebastian platelet syndrome, Epstein syndrome, and Fechtner syndrome derive from mutations of the same gene and describe overlapping disorders. Despite these advances, knowledge of hereditary thrombocytopenias is still far from satisfactory because for approximately half of the patients it is not possible to formulate a definite diagnosis in that their illnesses has not yet been described. In this review, we provide a systematic description of hereditary thrombocytopenias as we know them today, giving special attention to genetic aspects

On the efficacy of neuraminidase treatment in studies on red cell aging

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Cytoskeleton modifications depending on binding of thrombin to platelet surface

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Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias

MYH9-related disease (MYH9-RD) is one of the most frequent forms of inherited thrombocytopenia. It is transmitted in an autosomal dominant fashion and derives from mutations of MYH9, the gene for the heavy chain of non-muscle myosin IIA. Patients present with congenital macrothrombocytopenia with mild bleeding tendency and may develop kidney dysfunction, deafness and cataracts later in life. The term MYH9-RD encompasses four autosomal-dominant thrombocytopenias that were previously described as distinct disorders, namely May-Hegglin Anomaly, Sebastian, Fechtner and Epstein syndromes. Thrombocytopenia is usually mild and derives from complex defects of megakaryocyte maturation and platelet formation. It is easily diagnosed, in that the presence of giant platelets in peripheral blood raises the suspicion of MYH9-RD and a simple immunofluorescence test on blood films confirms the diagnostic hypothesis. However, genotype/phenotype correlations have been recognized and mutation screening is therefore required to define the risk of acquiring extra-haematological defects. Results of a small clinical study suggested that a non-peptide thrombopoietin mimetic might greatly benefit both thrombocytopenia and bleeding tendency of MYH9-RD patients