Abstract
A number of inherited and acquired factors modulate von Willebrand factor antigen (VWF:Ag) levels, including blood type, race, activity and stress level, thyroid hormone status, and, in women, time in menstrual cycle. In reported studies a positive correlation between VWF:Ag and/or factor VIII levels and age has been demonstrated, with an increase of 5 – 6 IU/dL per decade (Conlan MG et al, 1993; Kamphuisen PW et al, 1998). Those studies have primarily assessed VWF and factor VIII as risk factors for ischemic heart disease, cerebrovascular disease, and venous thromboembolism. None of the subjects had von Willebrand disease (VWD). Their VWF:Ag levels were in the higher normal or elevated range. The purpose of this study was to determine whether there is a relationship between age and VWF:Ag level in patients with Type 1 VWD. We collected the data from 36 patients who were diagnosed with type 1 VWD and followed at the Penn Comprehensive Hemophilia and Thrombosis Program up to a period of 13 years (See Table 1 below). For each patient, date of birth, VWF:Ag levels with corresponding test dates were collected by reviewing the medical histories and the lab results. Test results obtained during pregnancy, DDAVP testing, or during prophylaxis or therapy for bleeding control were excluded. One year was set as the observation period, so the adjacent VWF:Ag levels that were tested less than one year were excluded from the dataset. When two test results were available on a patient within a one-year period, the lower test result was used.
To investigate whether there was a relationship between VWF:Ag levels and age, cross-sectional analyses (across each visit) and longitudinal analyses were performed using scatter plots, Spearman and Pearson correlations, and regression analysis. No significant increase in VWF:Ag levels with age was demonstrated. The fact that we did not find an increase in VWF:Ag levels over time in our patients could be due to the relatively small number of patients studied or could reflect a subtype of VWD, due to our selection criteria. Only patients with abnormal values were included. Some patients have a prior diagnosis of VWD and bleeding symptoms, but have normal values when tested. Since these patients are adults, this may be due, at least in part, to an age-related increase. Type 1 VWD may occur secondary to decreased VWF synthesis and/or clearance. It is possible that age-related effects on VWF levels will differ depending on the underlying factor(s) resulting in a lower VWF level. Further studies correlating a patient’s values longitudinally with the underlying pathophysiology of their disease would aid in our understanding of their bleeding risks over time.
Patient # Age at Last Visit, range (mean) Females (%) Race % (Cauc/AA/Other) VWF:Ag mean 36 17–70 (34) 89 78/19/3 49%
Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery