Changes in von Willebrand factor level and von Willebrand activity with age in type 1 von Willebrand disease

Abstract

In a normal population, VWF plasma levels (VWF:Ag) and VWF activity (VWF:RCo) increase by approximately 0.17 and 0.15 IU/ml per decade, but the influence of age is unknown in patients with type 1 von Willebrand disease (VWD). In a retrospective cohort study, the medical records of 31 type 1 VWD patients over the age of 30, who had been followed for ≥5 years, were reviewed for baseline clinical data and previously performed VWF:Ag, VWF:RCo and factor VIII levels (FVIII:C). VWF multimer analysis was normal in 27/31 cases performed. Mean bleeding score was 9.4 (range 2-21). Mean age at diagnosis was 33 (range 16-60 years), and duration of follow-up ranged from 5-26 years (mean 11 years). Patients had 2-10 time points of VWD testing (mean of 5.2). The mean VWF:Ag, VWF:RCo and FVIII:C at time of diagnosis were 0.44 IU/ml 0.34 IU/ml and 0.75 IU/ml. At last follow-up, the mean VWF:Ag, VWF:RCo and FVIII:C were significantly increased to 0.71 IU/L, 0.56 IU/ml and 0.90 IU/ml (p=<0.001, <0.001, and 0.0081, respectively). 18/31 patients had VWF:Ag, VWF:RCo and FVIII:C levels that increased into the normal range. The rate of change in VWF:Ag and VWF:RCo was 0.30 IU/ml (0.214-0.386, CI 95%, p<0.0001) and 0.20 IU/ml per year (0.126-0.274, CI 95%, p=0.0001). Patients with type 1 VWD experience age-related increases to VWF:Ag and VWF:RCo which can result in normalization of VWF levels. Further studies are required to determine if the bleeding phenotype resolves with the increases in VWF:Ag and VWF:RCo levels.

von Willebrand disease and aging: an evolving phenotype

“…Our analyses of VWF and FVIII levels measured over time in a subset of elderly individuals showed that an increase with age also occurs in type 1 VWD patients, which is in accordance with a smaller recent study [22]. This longitudinally measured increase in VWF parameters with age within elderly patients was not found in type 2 VWD.…”

Increase of von Willebrand factor with aging in type 1 von Willebrand disease: fact or fiction?

“…In fact, gene mutations affecting the synthesis, processing and secretion of VWF are more frequently detected in the more severe VWD-1 cases, 10 and it is reasonable to presume that genetic defects of the synthesis or processing of VWF may not allow the expression of age-related increases. 4 Indeed, 117 out of 195 (60%) of the patients investigated in our series would not have been diagnosed with VWD-1 had they been studied only at the last observation point. Indeed, when subdividing patients by severity subgroup, while 94% of those initially labeled as mild had normal laboratory values at the last observation time, only 6% of those defined as moderate normalized.…”

Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States

“…There are a number of possible reasons for this lack of diagnostic fidelity. VWF levels increase with age, such that patients diagnosed many years prior to study entry may have "outgrown" their diagnosis [30][31][32] ; furthermore, the appropriate reference interval for an older adult is not well defined. Assays for VWF function may not be ideal, resulting in potential false positive or false negative laboratory results.…”