Do Activated Platelets Contribute to Mild Bleeding in Severe Hemophilia A?

About 15% of severe Hemophilia A (HA) patients exhibit occasional bleeding, without requiring continuous therapy. Since platelets are critical for thrombus formation, this study investigated whether platelets are activated in severe HA with mild bleeding, and if so, do they contribute to alter the clinical severity. 38 severe HA patients were enrolled in this cross-sectional investigation and classified as severe or mild bleeders based on the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) score. Platelet activation was evaluated using platelet surface markers such as Annexin-V and PAC-1. Additionally, platelet aggregation was assessed by platelet aggregometry to understand the presence of hyper-aggregation. Multivariate regression analysis and correlation analysis were performed to assess the associations of clinical covariates with platelet activation markers. Based on the ISTH-BAT score, 13.15% of severe patients were identified as mild bleeders. No significant platelet activation and hyper-aggregation were observed in mild bleeders when compared to severe bleeders. However, one mild bleeder exhibited increased surface expression of integrin αIIbβ3 and enhanced platelet aggregation, which may not be ignored for the possible role of activated platelets in modulating the clinical phenotype in severe HA. Age emerged as a significant predictor of platelet activation while no significant correlation was observed between ISTH-BAT and platelet activation markers. Although no significant platelet activation was observed in severe HA with mild bleeding, one mild bleeder with increased surface expression of αIIbβ3 and hyper-aggregation suggest a possible compensatory role, warranting further multicentred investigation.

The online version contains supplementary material available at https://doi.org/10.1007/s12288-025-02280-9.