Beyond Body Weight: Biological and Clinical Determinants of Factor VIII Pharmacokinetics in Tunisian Patients

Inter-individual variability in factor VIII (FVIII) pharmacokinetics (PK) is well recognized in people with haemophilia A (PWH-A) and may compromise the effectiveness of prophylaxis. This variability is partially explained by clinical and biological determinants, including age, anthropometric parameters and von Willebrand factor antigen (VWF:Ag) levels.

To identify the determinants of FVIII-PK in Tunisian PWH-A and assess their implications for PK-guided prophylaxis.

A prospective PK study was conducted in 25 people with severe or moderate haemophilia A enrolled between December 2022 and December 2024. Following a 72-hour wash-out, PWH-A received standard half-life FVIII concentrates. FVIII activity was measured using one-stage assay (OSA) and chromogenic substrate assay (CSA) at baseline, 30 min, 5 h ±1 h, 24 h and 48 h post-infusion. PK parameters-half-life, clearance, in vivo recovery and area under curve (AUC)- were calculated and correlated with age, anthropometric parameters, ABO blood group and VWF:Ag levels.

FVIII activity measured by OSA and CSA showed a strong correlation (p < 0.0001). Higher VWF:Ag levels were associated with longer FVIII half-life (p = 0.021) and lower clearance (p = 0.027). Body mass index (BMI) correlated positively with IVR (p = 0.007) while younger age was associated with higher clearance (p = 0.037). No significant differences in PK parameters were observed between plasma-derived and recombinant FVIII concentrates, except for higher AUC with plasma-derived concentrates.

FVIII PK in Tunisian PWH-A shows substantial inter-individual variability. VWF:Ag levels, age and BMI were associated with PK parameters, supporting the implementation of individualized PK-guided prophylaxis in Tunisia.