Comparison of Different Assays for von Willebrand Factor in Hemodialysis Patients

Abstract

Von Willebrand factor (vWF) abnormalities are involved in the hemostatic disturbances of uremia. Studies of vWF in both anemic and recombinant erythropoietin (EPO)-treated maintenance hemodialysis (HD) patients have given inconsistent results that could be partially dependent on the methodology. Therefore, the reciprocal relationships between four different vWF assays were studied in HD patients in relation to EPO therapy. Plasma vWF activity measured by ELISA using monoclonal antibodies against platelet glycoprotein (GP) Ibα (vWF:Act), plasma vWF antigen concentration by ELISA employing polyclonal antihuman vWF antibodies (vWF:Ag), and functional vWF activity by ristocetin-induced platelet aggregation (RIPA) in both platelet-rich plasma (PRP) and whole blood were studied in 70 HD patients. In the whole group, no correlations between these assays were found. In the non-EPO patients (n = 32), vWF:Act was correlated with vWF:Ag (r = 0.504, p = 0.003) but not with vWF activity by RIPA in PRP. In the EPO-treated patients (n = 38), vWF:Act was higher than in the untreated ones (p = 0.001), and vWF:Ag was related to the whole-blood RIPA (r = 0.386, p = 0.016). In conclusion, the platelet GP Ibα-binding epitope of the vWF molecule assessed by vWF:Act ELISA is intact in HD patients. However, this assay does not reflect the functional vWF activity as measured by RIPA in PRP. In EPO-treated patients, the GP Ibα-binding domains of vWF are more available but the plasmatic vWF monomers are neither more numerous by vWF:Ag ELISA nor more hemostatically active by RIPA PRP. The whole blood RIPA test has some potential for the quantification of vWF monomers in EPO-treated HD patients.

Effect of Unfractionated and Low-Molecular-Weight Heparin on OPG, sRANKL, and von Willebrand Factor Concentrations During Hemodialysis

“…Our work is consistent with many previous studies reporting higher levels of OPG 20 –24 and vWF 25 –27 in patients with chronic kidney disease. As vWF is an endothelial dysfunction marker and OPG is considered to be one, increased levels of these glycoproteins identify population with high cardiovascular risk.…”

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

“…Although there are a number of reports in the literature that confirm that vWF antigen levels are elevated in chronic disease states [4][5][6]9,[19][20][21][22][23], the hemostatic risk is better identified by considering both the quantity and activity of vWF and the vWF multimer pattern. We report significantly elevated vWF : Ag levels and vWF : RCo (indicating increased vWF activity) in dialysis patients.…”

“…It is well documented that vWF antigen levels are markedly elevated in patients with chronic kidney disease (CKD) [3][4][5][6][7][8][9][10][11][12]. This may be due to hyperstimulation of vWF endothelial secretion pathways as most circulating vWF is derived from the endothelium.…”

Inflammatory Markers and Platelet Aggregation Tests as Predictors of Hemoglobin and Endogenous Erythropoietin Levels in Hemodialysis Patients

“…The RIPA test when performed in platelet-rich plasma (PRP) estimates functional activity of circulating vWF [16], which is a mostly EC-derived multimeric glycoprotein involved in platelet adhesion and aggregation, and in blood coagulation [17]. On the other hand, the whole blood RIPA in HD patients gives a measure of plasma vWF concentration rather than of its activity [18]. Thus, based on our previous findings [12, 14, 15], we hypothesized that enhanced whole blood RIPA was a marker of EC inflammation leading to the exacerbation of anemia in maintenance HD patients.…”