Diagnosing Czech Patients with Inherited Platelet Disorders

Area of Science:

• Hematology
• Genetics
• Molecular Diagnostics

Background:

• Inherited disorders of primary hemostasis cause diverse bleeding symptoms.
• Many patients lack definitive diagnoses, impacting family screening and treatment.
• Advanced diagnostic methods are crucial for accurate diagnosis.

Purpose of the Study:

• To enhance the diagnostic rate in patients with inherited primary hemostasis disorders.
• To evaluate the utility of next-generation sequencing (NGS) in diagnosing these conditions.

Main Methods:

• Retrospective analysis of 120 patients with undiagnosed bleeding disorders.
• Application of conventional methods: platelet morphology, function assays, aggregometry, flow cytometry.
• Implementation of next-generation sequencing (NGS) in a subset of 31 patients.

Main Results:

• Conventional methods were insufficient for definitive diagnosis in most patients.
• NGS identified definitive diagnoses in 6 patients (variants in ANKRD26, ITGA2B, F8).
• NGS identified suspected and novel suspected variants in 11 additional patients across multiple genes.

Conclusions:

• Next-generation sequencing (NGS) is a powerful tool for diagnosing inherited bleeding disorders.
• NGS offers a higher diagnostic yield compared to traditional methods.
• Gene variants of uncertain significance remain a challenge in NGS interpretation.