Clinical and Genetic Characterization of 269 Patients With Suspected Inherited Platelet Disorders: The Padua Monocentric Experience.

Abstract

Background: Inherited platelet disorders (IPDs) are rare hematologic conditions encompassing a heterogeneous spectrum of quantitative and qualitative platelet defects, frequently associated with variable clinical phenotypes and comorbidities. Accurate diagnosis necessitates comprehensive genetic characterization, detailed clinical and bleeding history, and systematic evaluation of platelet count, size, and function, which are essential to distinguish IPDs from immune thrombocytopenia (ITP).

Aim: The aim of this study was to clinically and genetically characterize a total of 269 patients from 140 families with platelet disorders, evaluated at the First Chair, Department of Medicine, University of Padua.

Methods: Patients with suspected platelet disorders underwent comprehensive laboratory evaluation, and Sanger sequencing was performed to identify causative variants in approximately 30% of cases.

Results: We identified 80 patients from 44 families who were found to carry pathogenic or likely pathogenic variants, with the most frequent ones being linked to Bernard-Soulier syndrome (BSS), characterized by thrombocytopenia and bleeding tendency. Additionally, 23 subjects had MYH9 gene variants and one patient was affected by Glanzmann thrombasthenia. We also discovered seven pathogenic variants not previously described in the literature.

Conclusion: Due to the limitations of the Sanger method, the molecular defect could only be defined in approximately 30% of cases. In the remaining 70% of patients, the genetic cause remained unidentified, highlighting the need for further evaluation using an extended NGS panel targeting genes associated with inherited thrombocytopenias.