Upregulation of Von Willebrand Factor, Von Wilelbrand Factor Propeptide, and ADMATS-13 In End-Stage Renal Disease

Abstract 5189

End-Stage Renal Disease (ESRD) is a complex syndrome in which systemic vascular pathophysiologic changes contribute to adverse cardiovascular and cerebrovascular manifestations. Cardiovascular disease alone is present in over 60% of patients with ESRD and contributes heavily to mortality among this population. Von Willebrand Factor (vWF) plays a well known role in platelet aggregation and has been shown to be upregulated in many thromboembolic conditions. However in many conditions, the role of von Willebrand Factor Propeptide (vWFpp), a peptide cleaved prior to assembly of active vWF multimers, and ADAMTS-13, the enzyme responsible for disassembly and deactivation of vWF multimers, have not been examined. The purpose of this study is to better characterize the relationship among vWF, vWFpp, and ADAMTS-13 as it relates to ESRD. Plasma samples from 51 patients with ESRD were collected prior to maintenance hemodialysis. A group of 50 normal individuals, both male and female, was included as control. Concentrations of vWF and vWFpp were quantified using the GTI® vWF & Propeptide Assay. A separate assay was used to measure ADAMTS-13 in these samples (GTI®). This data as well as the ratio of vWF:vWFpp were analyzed using the Mann-Whitney U test (two-tailed with Gaussian approximation). Compared to the controls, there was an upregulation of all three analytes in patients with ESRD. Levels of vWF were increased 1.3 fold, (mean 128 ± 69 U/dL, range 9.2 to 308) compared to control (mean 101 ± 60, range 22 to 332). Similarly, there was a 1.6 fold increase in both vWFpp (mean 148 ± 92, range 8.0 to 361) compared to (mean 92 ± 23, range 60 to 163) and ADAMTS-13 (mean 131 ± 27, range 67 to 150) compared to (mean 84 ± 22, range 36 to 128). However, the ratio of vWFpp:vWF (mean 1.2 ± 0.6, range 0.4 to 3.3) was unchanged compared to control (mean 1.2 ± 0.7, range 0.4 to 3.6). This study shows a previously uncharacterized increase in vWFpp and further validates the upregulation of vWF in ESRD. The normal vWFpp:vWF ratio implies an increased production in vWF in response to endothelial damage without any apparent alteration in vWF degradation or clearance. The proportional increase in ADAMTS-13 activity suggests that the increased vWF is being cleaved into inactive monomers. However, further studies are required to assess the proportion of vWF in each mulitmeric form and better understand the exact interaction among these components in ESRD.