1,721,019 research outputs found
Inherited thrombocytopenias: an updated guide for clinicians
No full textThe great advances in the knowledge of inherited thrombocytopenias (ITs) made since the turn of the century have significantly changed our view of these conditions. To date, ITs encompass 45 disorders with different degrees of complexity of the clinical picture and very wide variability in the prognosis. They include forms characterized by thrombocytopenia alone, forms that present with other congenital defects, and conditions that predispose to acquire additional diseases over the course of life. In this review, we recapitulate the clinical features of ITs with emphasis on the forms predisposing to additional diseases. We then discuss the key issues for a rational approach to the diagnosis of ITs in clinical practice. Finally, we aim to provide an updated and comprehensive guide to the treatment of ITs, including the management of hemostatic challenges, the treatment of severe forms, and the approach to the manifestations that add to thrombocytopenia
Genetics of familial forms of thrombocytopenia
No full textThe 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
Thrombopoietin receptor agonists in hereditary thrombocytopenias
No full textHereditary thrombocytopenias (HTPs) constitute a heterogeneous group of diseases characterized by a reduction in platelet count and a potential bleeding risk. As a result of advances in diagnostic methods, HTPs are increasingly being identified, and appear to be less rare than previously thought. Most HTPs do not have effective treatments, except for platelet transfusion when bleeding occurs and in preparation for procedures associated with a risk of bleeding. Preliminary clinical evidence suggests that thrombopoietin receptor agonists (TPO-RAs) with an established use in the treatment of certain acquired thrombocytopenias are well tolerated and provide clinical benefits in patients with some forms of HTP. These drugs may therefore be considered for the treatment of HTPs in clinical practice. However, caution and close monitoring are recommended, owing to the absence of long-term safety data and the potential risks posed by prolonged bone marrow stimulation in certain HTPs. In this review, we summarize the available clinical data on TPO-RAs in the treatment of HTPs, and discuss their use in patients with these disorders. We believe that TPO-RAs will play a major role in the treatment of HTPs, particularly myosin heavy chain 9-related disease, Wiskott-Aldrich syndrome, X-linked thrombocytopenia, and thrombocytopenia caused by THPO mutations
Recent advances in the understanding and management of MYH9-related inherited thrombocytopenias
No full textMYH9-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
Bleeding is not the main clinical issue in many patients with inherited thrombocytopaenias
No full textBleeding diathesis has been considered for a long time the main clinical issue impacting the lives of patients affected by inherited thrombocytopaenias. However, the number of known inherited thrombocytopaenias greatly increased in recent years, and careful evaluation of hundreds of patients affected by these 'new' disorders revealed that most of them are at risk of developing additional life-threatening disorders during childhood or adult life. These additional disorders are usually more serious and dangerous than low platelet count. For instance, it is known that mutations in RUNX1, ANKRD26 and ETV6 cause congenital thrombocytopaenia, but we now know that they also predispose to haematological malignancies. Similarly, MYH9 mutations result in congenital thrombocytopaenia and increase the risk of developing kidney failure, cataracts and hearing loss at a later stage, while MPL mutations cause a congenital thrombocytopaenia that almost always evolves into deadly bone marrow failure. Thus, identification of patients with these disorders is essential for evaluation of their prognosis, enabling effective genetic counselling, personalizing follow-up and giving appropriate treatments in case of development of additional diseases. Careful clinical evaluation and peripheral blood film examination are extremely useful tools in guiding the diagnostic process and identifying the candidate genes to be sequenced
Eltrombopag in preparation for surgery in patients with severe MYH9-related thrombocytopenia
No full textPatients with inherited thrombocytopenias often require platelet transfusions to raise platelet count before surgery or other invasive procedures; moreover, subjects presenting clinically significant spontaneous bleeding may benefit from an enduring improvement of thrombocytopenia. The hypothesis that thrombopoietin-mimetics can increase platelet count in inherited thrombocytopenias is appealing, but evidence is scarce. We conducted a prospective, phase 2 clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia. We enrolled 24 patients affected with MYH9-related disease, ANKRD26-related thrombocytopenia, X-linked thrombocytopenia/Wiskott-Aldrich syndrome, monoallelic Bernard-Soulier syndrome, or ITGB3-related thrombocytopenia. Average pre-treatment platelet count was 40.4 x109/L. Patients received a 3- to 6-week course of eltrombopag in a dose-escalation manner. Of 23 patients evaluable for response, 11 (47.8%) achieved a major response (platelet count >100 x109/L), 10 (43.5%) a minor response (platelet count at least twice than baseline), whereas 2 patients (8.7%) did not respond. Average increase of platelet count compared to baseline was 64.5 x109/L (p<0.001). Four patients who presented clinically significant spontaneous bleeding were admitted to a long-term eltrombopag administration (16 additional weeks): all of them obtained remission of mucosal hemorrhages that persisted throughout the treatment period. Treatment was globally well tolerated: 5 patients reported mild adverse events and one patient a moderate adverse event. In conclusion, eltrombopag was safe and effective in increasing platelet count and reducing bleeding symptoms in different forms of inherited thrombocytopenia. Despite these encouraging results, caution is recommended when using thrombopoietin-mimetics in inherited thrombocytopenias predisposing to leukemia
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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