Age, but not blood group or von Willebrand factor (VWF) levels, was weakly associated with factor VIII (FVIII) levels in patients with nonsevere hemophilia A, according to a study published in the Journal of Thrombosis and Haemostasis.

Researchers conducted an observational, cross-sectional study across 4 Austrian hemophilia centers to investigate the effects of blood group, VWF levels, and age on variability in FVIII levels, which would influence the assessment of severity in nonsevere hemophilia A.

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For 89 patients with hemophilia A, the lowest FVIII level from each patient’s history served as a basis for diagnosis and assessment of severity. Blood samples were taken during a routine visit to assess FVIII clotting activity (FVIII:C) with the one-stage clotting assay (OSA) and the chromogenic substrate assay (CSA), FVIII (FVIII:Ag) and VWF (VWF:Ag) antigens, and VWF activity (VWF:Act). The researchers also recruited 82 healthy control individuals.

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In patients with hemophilia A, no differences were observed between those with blood group O compared with those with non-O blood groups in FVIII:C OSA (14.1 vs 15.5), CSA (10.0 vs 10.0), and FVIII:Ag (15.2 vs 15.2). In contrast, non-O individuals in the control group had significantly higher FVIII levels compared with those with blood group O (FVIII:C OSA, 150.0 vs 109.5; P <.001).

FVIII:C and VWF levels were not correlated in patients with hemophilia A but were correlated in healthy controls (Spearman’s rho, 0.79; P <.001). Although age had a minor influence on FVIII:C in patients with hemophilia A, it had a strong influence in healthy controls. In multivariable regression analysis, there was a significant association between blood group, VWF:Ag, age, and FVIII:C (P <0.001) that accounted for 61.3% of the variation in FVIII:Act.

“We conclude that for the assessment of FVIII levels in patients with mild or moderate haemophilia A, neither the [blood group] nor the VWF level have to be taken into account,” wrote the researchers. “Age has to be considered a minor modification factor, as there is a consistent, but weak, increase in FVIII levels with age.”


1.     Rejtö J, Königsbrügge O, Grilz E, et al. Influence of blood group, von Willebrand factor levels and age on factor VIII levels in non‐severe haemophilia A [published online February 19, 2020]. J Thromb Haemost. doi: 10.1111/jth.14770