Myeloid Cell Function and Cytokine Profiles in Paediatric Haemophilia A: Insights From FVIII and Emicizumab Prophylaxis

Haemophilia A (HA) is an X-linked bleeding disorder caused by factor VIII (FVIII) deficiency, treated with FVIII infusions or, more recently, Emicizumab subcutaneously. Although Emicizumab is safe and effective, FVIII is still required for severe bleeding, trauma, or surgery, and few studies have compared these prophylactic options in paediatric patients. This study explores the immunological and haematological profiles of paediatric HA patients receiving FVIII or Emicizumab, using haemophilia B patients and healthy controls. Clinical parameters and immune cell populations showed no major differences aside from age-related variations. However, HA patients displayed higher HLA-DR expression on CD14⁺ cells than healthy controls, and Emicizumab-treated patients showed increased HLA-DR expression on CD11c⁺ cells compared with FVIII-treated patients. Plasma cytokines including IL-12p40, TNF-α, CCL-22, IL-18, and CCL-4 were elevated in HA, suggesting a dysregulated myeloid compartment in HA. Patient-derived macrophages exhibited a stronger pro-inflammatory (M1-like) polarization after in vitro FVIII stimulation, with increased TNF-α and reduced TGF-β gene expression. Stratification by prophylaxis showed that macrophages from FVIII-treated patients maintained the M1 phenotype, whereas those from Emicizumab-treated patients showed no clear shift and tended toward an immune-regulatory profile. These findings highlight distinct myeloid and cytokine signatures associated with different prophylaxis, emphasizing the need for optimized therapeutic strategies.