Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup.

Inherited thrombocytopenias (IT) are genetic diseases characterized by low platelet count, sometimes associated with congenital defects or a predisposition to develop additional conditions. Next-generation sequencing has substantially improved our knowledge of IT, with more than 40 genes identified so far, but obtaining a molecular diagnosis remains a challenge especially for patients with non-syndromic forms, having no clinical or functional phenotypes that raise suspicion about specific genes. We performed exome sequencing (ES) in a cohort of 116 IT patients (89 families), still undiagnosed after a previously validated phenotype-driven diagnostic algorithm including a targeted analysis of suspected genes.

Treatment of inherited thrombocytopenias.

The new techniques of genetic analysis have made it possible to identify many new forms of inherited thrombocytopenias (IT) and study large series of patients. In recent years, this has changed the view of IT, highlighting the fact that, in contrast to previous belief, most patients have a modest bleeding diathesis. On the other hand, it has become evident that some of the mutations responsible for platelet deficiency predispose the patient to serious, potentially lifethreatening diseases.

Miniaturized 3D bone marrow tissue model to assess response to Thrombopoietin-receptor agonists in patients.

Thrombocytopenic disorders have been treated with the Thrombopoietin-receptor agonist Eltrombopag. Patients with the same apparent form of thrombocytopenia may respond differently to the treatment. We describe a miniaturized bone marrow tissue model that provides a screening bioreactor for personalized, pre-treatment response prediction to Eltrombopag for individual patients.

Inherited thrombocytopenias: an updated guide for clinicians.

The 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.

Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial.

Patients with inherited thrombocytopenias often require platelet transfusions to raise their platelet count before surgery or other invasive procedures; moreover, subjects with 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 II clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia.