Quantitative and qualitative changes of von Willebrand factor and their impact on mortality in patients with end-stage kidney disease.

von Willebrand factor (vWF) antigen levels are elevated in patients with end-stage kidney disease (ESKD). We determined the quantitative and qualitative abnormalities of vWF and factors influencing vWF proteolysis in participants with ESKD compared with age-matched controls and determined the association between abnormalities in vWF and mortality over 4 years of follow-up. vWF : Ag and von Willebrand factor propeptide (vWFpp) levels, vWF functional activity (vWF :RCo), vWF multimer profiles, ADAMTS-13, thrombospondin 1 (TSP-1), and interleukin 6 (IL-6) were evaluated before and after a single hemodialysis treatment in 55 individuals with vascular disease and an age-matched group of controls (n = 21). vWF : Ag and vWF activity were significantly higher in the ESKD patients and levels increased further following the dialysis procedure. The percentage of high molecular weight multimers (%HMWMs) was significantly elevated in the ESKD patients compared with controls. TSP-1 was lower and IL-6 was higher providing possible explanation for the increase in %HMWM in ESKD. The %HMWM dropped significantly in the postdialysis sample. Mortality at 4 years was significantly associated with vWF : Ag. There are higher plasma vWF : Ag levels and a small increase in HMWMs in the ESKD milieu. The acute drop in the %HMWM of vWF postdialysis appears to be due to shear forces encountered during the dialysis procedure. The contribution of these abnormalities to either a pro-thrombotic and/or pro-bleeding phenotype in this population requires further study.