PB1240 - Inherited Platelet Disorders Associated With Platelet Membrane Glycoproteins Abnormalities: A Portuguese Centre Experience

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Patricia Martinho, PhD

Biologist - Laboratory Assistant
Unidade Funcional de Hematologia Moleculat, Serviço de Hematologia Clínica, CHUC
Coimbra, Coimbra, Portugal

Co-Author(s)

CP

Catarina Pinto

Laboratory Assistant
Unidade Funcional de Hematologia Molecular, Serviço de Hematologia Clínica, CHUC
Coimbra, Coimbra, Portugal
JC

Joana Cabral

Medical Doctor
Serviço Imunohemoterapia, Hospital de Braga
Braga, Braga, Portugal
JA

Joana Azevedo

Medical Doctor
Unidade Funcional de Hematologia Molecular, Serviço de Hematologia Clínica, CHUC
Coimbra, Coimbra, Portugal
AR

Adriana Roque

Medical Doctor
Unidade Funcional de Hematologia Molecular, Serviço de Hematologia Clínica, CHUC
Coimbra, Coimbra, Portugal
OL

Olena Lavrukhina

Medical Doctor
Blood and Transfusion Medicine Department, Hemophilia Reference Centre, Centro Hospitalar e Universitário de Coimbra
Coimbra, Coimbra, Portugal
Cristina Catarino, Dr

Doctor
Centro Hospitalar Universitário Lisboa Norte
Lisboa, Lisboa, Portugal
FR

Fátima Rodrigues

Medical Doctor
Serviço de Imunohemoterapia, Hospital Santa Maria
Lisboa, Lisboa, Portugal
EA

E.M. Antunes

Medical Doctor
Serviço de Imunohemoterapia, Hospital São José
Lisboa, Lisboa, Portugal
SB

Sara Batalha

Medical Doctor
Serviço de Pediatria, Hospital Dona Estefania
Lisboa, Lisboa, Portugal
SF

Susana Fernandes

MD
Immunohemotherapy Department, Centro Hospitalar Universitário de São João, Porto, Portugal
Porto, Porto, Portugal
ML

Manuela Lopes

MD
Immunohemotherapy Department, Centro Hospitalar Universitário de São João, Porto, Portugal
Porto, Porto, Portugal
CG

Catarina Geraldes

Clinical Hematology Department Director
Clinical Hematology Department, Centro Hospitalar e Universitário de Coimbra
Coimbra, Coimbra, Portugal
TF

Teresa Fidalgo

Laboratory Coordinator
Unidade Funcional de Hematologia Molecular, Serviço de Hematologia Clínica
Coimbra, Coimbra, Portugal

Background: Inherited platelet disorders, affecting either platelet functions or platelet count are a heterogeneous group of rare inherited disorders, and a molecular diagnosis is especially relevant to proper clinical management.
The most frequent molecular abnormalities in genes coding platelet membrane glycoproteins are: i) GP1BA, GP1BB and GP9 (Bernard-Soulier Syndrome (BSS) or dominantly inherited macrothrombocytopenia (monoallelic BSS); ii) ITGA2B and ITGB3 (Glanzmann thrombasthenia (GT), GT-like syndrome (GT-like) and autosomal dominant macrothrombocytopenia (ATMD).

Aims: Improve the molecular diagnosis of patients with suspected glycoprotein abnormalities and/or haemorrhagic diathesis of unknown cause by next generation sequencing (NGS).

Methods: Twenty-two unrelated patients [median age 39 years (4-70), 17F] and 10 relatives were analyzed. The molecular diagnosis was done using a custom panel for NGS (43 genes). Library preparation and sequencing was done using IonS5 protocol (Thermo Fisher Scientific).

Results: We have identified 23 different variants (pathogenic, potentially pathogenic, and unknown significance variant) in GP1BA (n=3), GP9 (n=3), ITGA2B (n=8) and ITGB3 (n=9) genes, including eight new variants. The patients diagnosed as BSS (n=3) and GT (n=5) were homozygous or compound heterozygous for 2 variants in GP9, 1 in GP1BA, 5 in ITGB3 and 1 in ITGA2B. These patients had more severe haemorrhagic manifestations (BS: 8-14). The remaining 14 heterozygous patients were diagnosed as GT-like (n=7; BS:2-11) monoallelic BSS (n=2; BS:0-2), and ATMD (n=5; BS:0-3). Some variants were previously reported in association with monoallelic BSS, GT-like syndrome and ATMD (Table1).

Conclusion(s): A phenotype-genotype correlation was observed in all patients, not only in the more severe forms (BSS and GT), but also, in the milder ones (monoallelic BSS, GT type and ATMD).
Our work broadens the spectrum of variants identified in BSS and GT, underlying the importance of genetic testing in recognizing both monoallelic and biallelic forms of these disorders, allowing a better clinical care, prognosis, and preventive treatments.