Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS)

Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) a re not unequivocal. Because of potential pathogenic implications, we examin ed the ability of vWF to bind to collagen in vitro, which reflects its func tion. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) w ere measured by enzyme-linked immunosorbent assay in children with (1) diar rhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immun e thrombocytopenia (TTP) (n = 40) and from controls (n = 35). Structural vW F was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2. 53 and vWF:CBA of 1.98 U/mL, The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). T he mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only childre n with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; th e ratio was elevated in children with ITP (1.36) and GE (1.27) and was norm al in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vW F, caused either by a primary (due to enterohemorrhagic Escherichia coli) o r secondary (due to consumption of functionally active vWF) process. This a bnormality was not obvious as structural anomaly by multimer analysis.