Inherited thrombocytopenias (ITs) are rare conditions characterized by low platelet count resulting in impaired hemostasis.

Recent advances revealed that several forms expose patients to the risk of developing additional and life-threatening disorders. Making a definite diagnosis is essential to identify patients' prognosis, personalize follow-up and treatment. Furthermore, Eltrombopag, an oral drug mimicking thrombopoietin (THPO), was able to increase the number of platelets in most of the few patients treated so far. Despite these advances, knowledge on ITs is still unsatisfactory, in that nearly half of patients have yet unknown forms. Moreover, the individual patient's response to Eltrombopag can't be predicted. This project wants to improve knowledge on ITs by two approaches: identification and characterization of new ITs; an in vitro bone marrow model not only for pre-clinical pharmacological studies of innovative drugs, but also for predicting individual response to treatment.

The major problems when dealing with Inherited thrombocytopenias (ITs) are:

1. achieving a diagnosis of certainty;
2. setting up a personalized and effective treatment.

a) Near 50% of subjects remain without a diagnosis because they don't fit the diagnostic criteria for any known IT and don't have mutations in the causative genes identified so far. Our project, aimed at identifying new ITs by whole exome sequencing(WES) of a large number of subjects with unknow forms, will fill this gap; b)We want to improve therapy for ITs, which is presently mainly based on platelet transfusion, by the identification of new drugs and the usage of an innovative tool to predict in vitro patients' response to different treatment, allowing us to personalize therapeutic approaches.

Inclusion Criteria:

1. Exclusion of any known IT after the application of a validated diagnostic algorithm based on clinical and laboratory criteria;
2. Absence of mutations in genes known to be causative for IT;
3. Acquisition of written informed consent.

Exclusion Criteria:

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All patients affected with an IT who have not received a diagnosis of certainty will be considered eligible for enrollment, despite the application of a validated diagnostic algorithm.