Increasing levels of von Willebrand Factor and factor VIII with age in patients affected by von Willebrand disease

Background Increasing levels of von Willebrand factor (VWF) and factor VIII (FVIII:C) was associated with age in type 1 von Willebrand disease (VWD). Objectives To evaluate VWF and FVIII:C increase with age in a large group of patients with VWD and low levels of VWF, in whom levels were repeatedly measured. Methods Clinical charts from all patients evaluated at the A. Bianchi Bonomi Center between 1970 and 2018 were reviewed and data on VWF and FVIII:C collected. Patients affected by type 3, severe type 1 and 2N VWD were excluded. The repeated measurements were evaluated by linear mixed-effects models. A linear association between age and VWF/FVIII:C was shown after the age of 40 years in the linear mixed models and analyzed by calculating the regression slope coefficient (beta). Results A total of 617 patients were included in the study (314 type 2, 112 type 1, 181 low VWF levels), with a median age at first measurement of 28 years (interquartile range 14/42) and a mean follow-up of 16 years (standard deviation 11). VWF and FVIII:C increased with age in the whole group. The increase became linear after the age of 40 years (3.68 and 7.44 IU/dL per decade for VWF:activity and FVIII:C). In type 2, FVIII:C increased with age, whereas an increase of both VWF:activity and FVIII:C were shown in patients with type 1 VWD and low levels of VWF. Conclusions A differential increase of VWF and FVIII:C with age was shown among in different ages and types of VWD.