PB1293 - Genetic Landscape of Inherited Thrombocytopenia: Eight Years of Experiences in a Large Polish Cohort

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Co-Author(s)

BU

Bartosz Urbański

MD
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Lodz, Lodzkie, Poland

Co-Author(s)

KB

Katarzyna Bąbol-Pokora

MSc, PhD, Head of Medical Laboratory for Pediatric Oncology and Hematology, "Oncolab"
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland
AP

Agata Pastorczak

MD, PhD, University Professor
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland
SJ

Szymon Janczar

MD, PhD, University Professor
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland
OW

Olga Wegner

MD, PhD
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland
MW

Magdalena Wojdalska

MD, PhD
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland
MC

Magdalena Cienkusz

MD, PhD
Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Poland
Lublin, Lubelskie, Poland
AK

Agnieszka Kamela

MD
Department of Pediatrics, Institute of Medical Sciences, Medical College, University of Rzeszow, Rzeszow, Poland
Rzeszów, Podkarpackie, Poland
MR

Monika Richert-Przygońska

MD, PhD
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland
Bydgoszcz, Kujawsko-Pomorskie, Poland
GW

Grażyna Wróbel

MD, PhD
Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Poland
Wrocław, Dolnoslaskie, Poland
MJ

Michalina Jezierska

MD
Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Poland
Gdańsk, Pomorskie, Poland
KC

Krzysztof Chojnowski

Department of Haemostasis and Haemostatic Disorders
Medical University of Lodz, Poland
Łódź, Lodzkie, Poland

Presenting Author(s)

WM

Wojciech Młynarski

MD, PhD, Professor, Head of Department of Pediatrics, Oncology and Hematology
Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Poland
Łódź, Lodzkie, Poland

Background: Molecular diagnostics of inherited thrombocytopenia (IT) has emerged recently as the most challenging among congenital hemostasis disorders. Despite the identification of nearly 50 IT-related genes, the driver mutations often remain elusive. Diagnosis of IT is frequently delayed until adulthood due to the typically mild or asymptomatic nature and unsatisfactory awareness of the disease.

Aims: This study aimed to characterize the molecular background of IT genetically diagnosed at a reference laboratory in Poland.

Methods: The study included 162 patients with chronic thrombocytopenia since birth/childhood referred for genetic work-up to the Medical Laboratory for Pediatric Oncology and Hematology “Oncolab” in Lodz, Poland, between 2016 and 2023. Targeted next-generation sequencing on a panel of 750 genes, including IT-related ones (according to the Thrombogenomics Project standard), was performed. Subsequently, bioinformatic analysis and copy-number genomic studies were conducted, if necessary.

Results: The median age of the study group was 8.81 years (1.94-14.65), with pediatric patients accounting for 92% (n=149). The molecular background was identified in 56% of the patients (n=91). Among that group, 63 cases were associated with pathogenic variants in IT genes, according to the Bleeding Thrombotic and Platelet Disorder TIER1 genes (ISTH Gold Variants Project). The most common defects were found in the MYH9 (n=16;26%) and WAS genes (n=13;21%). Mutations predisposing to malignancies or bone marrow aplasia were identified in 11 patients (17%). In the remaining 28 patients, we demonstrated pathogenic variants potentially correlating with thrombocytopenia. The genetic basis of IT remained unknown in 44% (n=71) of the patients (Figure 1.).

Conclusion(s): The genetic testing results in Poland align with global trends. The use of reference methods enables the identification of the molecular background in most patients. Continued advancement and dissemination of genetic diagnostics, particularly in children, are crucial for improving their quality of life and implementing appropriate surveillance and genetic counseling for individuals with cancer-predisposing defects.