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

1University of Perugia, Perugia, Umbria, Italy, 2University of Perugia, Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine, Perugia, Umbria, Italy, 3Catholic University of Sacred Heart, Translational Medicine and Surgery Department, Rome, Lazio, Italy, 4Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Baden-Wurttemberg, Germany

Abstract Number: VPB0204

Meeting: ISTH 2022 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Basic

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.

To cite this abstract in AMA style:

Bury L, Kuchi Bhotla H, Piroli G, Cesari E, Falcinelli E, Guglielmini G, De Cristofaro R, Zieger B, Gresele P. Association between platelet receptor genotypes and the bleeding tendency of hemophilia patients [abstract]. https://abstracts.isth.org/abstract/association-between-platelet-receptor-genotypes-and-the-bleeding-tendency-of-hemophilia-patients/. Accessed September 21, 2023.

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