VPB0204 - Association between platelet receptor genotypes and the bleeding tendency of hemophilia patients

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: Virtual

Presenting Author(s)

Loredana Bury, PhD

Researcher
Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia
Perugia, Umbria, Italy

Co-Author(s)

HK

Haripriya Kuchi Bhotla

PhD student
University of Perugia, Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine
Perugia, Umbria, Italy
GP

Guido Piroli

PhD student
University of Perugia, Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine
Perugia, Umbria, Italy
EC

Enrica Cesari

PhD student
University of Perugia
Perugia, Umbria, Italy
EF

Emanuela Falcinelli

Post Doc
Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia
Perugia, Umbria, Italy
GG

Giuseppe Guglielmini

Biologist, PhD
Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, University of Perugia
Perugia, Umbria, Italy
RD

Raimondo De Cristofaro, MD, PhD

Professor, Haemostasis and Thrombosis Center Director
1.Fondazione Policlinico Universitario A. Gemelli, IRCCS, Center for Hemorrhagic and Thrombotic Diseases and Haemophilia Center, Rome, Italy; 2. Catholic University, Translational Medicine and Surgery Department Rome, Italy
Roma, Lazio, Italy
BZ

Barbara Zieger

Head of the Section Haemostaseology
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg
Freiburg, Baden-Wurttemberg, Germany
Paolo Gresele, MD, PhD

Professor
Dept. of Medicine and Surgery, University of Perugia
Perugia, Umbria, Italy

Background: Hemophilia bleeding severity is classified by residual factor activity as mild, moderate and severe. This classification, however, is not an entirely reliable predictor of the bleeding phenotype of individual patients. Little information is available on the contribution of platelets to the severity of the bleeding phenotype of patients with haemophilia, but some observations suggest a possible compensating function of increased platelet reactivity.
Common single nucleotide variants (SNVs) of platelet receptors have been shown to account for interindividual differences in platelet reactivity in normal individuals and the bleeding and thrombotic risk in some chronic disorders. These variants may also play a role in determining clinical disease severity in hemophilia.

Aims: Aim of our work was to investigate if common SNVs influencing platelet reactivity have a different distribution in hemophiliacs with similar residual factor levels but with different bleeding phenotypes.

Methods: 55 patients with haemophilia A or B were enrolled and their bleeding score (BS) was calculated using the ISTH-BAT. Blood was collected in sodium citrate and DNA was extracted. SNVs of ITGB3 (rs5918), ITGA2B (rs5911), ITGA2 (rs1126643 and rs1801106), GP6 (rs1613662), SELP (rs6136), ADRA2A (rs553668) and FCGR2A (rs1801274) were analyzed by PCR and Sanger sequencing.

Results: BS was significantly higher in hemophiliacs carriers of the SELP rs6136 A/C (BS A/A=8±7 vd A/C=12±5) and the FCGR2A rs1801274 G/G and A/G (BS A/A=7.5±3.5 vs A/G+G/G=13±6.6), previously associated with decreased platelet reactivity, despite similar residual factor levels. A combination of “platelet inhibiting” genotypes (FCGR2A rs1801274 A/G+G/G; SELP rs6136 A/C; ITGB3 rs5918 T/T) had a significantly higher prevalence in high bleeders and was associated with higher bleeding score (OR=4.9; 95% CI 1.1733 to 20.4798, p=0.029).

Conclusion(s): These results show for the first time that common genetic variants modulating platelet reactivity influence the bleeding phenotype of haemophilic patients, suggesting that platelet genotyping of hemophiliacs may help to formulate prognostic predictions.