Outgrowing the laboratory diagnosis of type 1 von Willebrand disease: A two decade study

Von Willebrand Factor (VWF) levels are known to increase with age in the general population, but that effect is unclear in von Willebrand disease (VWD) patients. Thus, it is important to assess the trends of VWF levels with age, and the extent and rate of their normalization in patients with VWD. In a retrospective cohort study, we reviewed the medical records of 126 patients between 1996 and 2016 who met the NHLBI diagnostic criteria for type 1 VWD or "Low VWF" (LVWF). We followed all their historically documented VWF antigen (VWF:Ag), VWF activity (VWF:RCo), and Factor VIII (FVIII) levels longitudinally over time, correlating data with clinical setting at time of testing. The average duration of follow-up was 10.5 ± 3.7 years (SD). Out of the total study population, 27.8% achieved the primary outcome of complete normalization (CN) of both VWF:Ag and VWF:RCo levels, including 19.6% and 32.5% of those with VWD and LVWF, respectively. Linear regression demonstrated statistically significant positive trends of VWF:Ag, VWF:RCo, FVIII with time, calculated at 2.4, 1.4, and 1.4 U dL-1/year, respectively (P < .001 each). In the largest study population of VWD patients to date whose levels were followed longitudinally, there is a statistically significant rise in VWF:Ag, VWF:RCo, and FVIII levels observed with time. CN of both VWF:Ag and VWF:RCo levels was observed in almost a third of patients with VWD or LVWF, over an average of 10 years. Whether the bleeding phenotype also improves is unclear and requires further study.