Age-dependent increase of FVIII:C in mild haemophilia A

Variability of FVIII:C levels in healthy individuals and age-dependent increase are a known phenomenon. In haemophilia, increasing FVIII:C levels with age have not been described yet. In our study, we evaluated this issue retrospectively in a cohort older than 45 years of 29 patients with mild haemophilia and 14 patients with moderate or severe haemophilia at last visit at the haemophilia centre Frankfurt. The median duration of observation evaluated in this study was 17 years (range 5-28). Results show a significant correlation of increasing FVIII:C levels with age in mild haemophilia (P = 0.000041) and a non-significant tendency to a higher increase in higher age (P = 0.085652). The median difference of FVIII:C level between the first and last measurement was 8% of normal plasma concentration (range -3% to +35%). Median FVIII:C level increase of patients younger than 62 years was 7.5% (range -3 to 22), median increase in older patients was 12% (range 0-35). This tendency could not be correlated to decreased number of bleedings, but FVIII substitution dosage should be adapted to changing plasma levels at higher age to prevent overdosing or thrombotic risks. Possible causes and contributing factors for increasing FVIII:C levels are discussed. Statistical significance remains to be confirmed in larger prospective studies also including younger patients.