Unrecognized pattern of von Willebrand factor abnormalities in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura

Heterogeneous abnormalities in multimeric structure and fragmentation of en dothelial-derived von Willebrand factor (vWF) have been reported in hemolyt ic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Thi s study was conducted to establish whether different patterns of vWF abnorm alities were associated with different clinical syndromes. Plasmatic levels of vWF antigen (vWF:Ag), VWF release from endothelial cells (EC) exposed t o patient sera, and vWF multimeric pattern were studied during episodes and again in remission in three groups of patients with severe forms of HUS an d TTP paradigmatic of the most common clinical patterns of disease presenta tion: (1) plasma-responsive; (2) plasma-resistant; and (3) frequently relap sing. Plasma vWF:Ag and serum-induced VWF release from EC were increased in the acute phase of either plasma-responsive and plasma-resistant HUS and T TP, but normalized at remission only in plasma-responsive cases. Both indic es were persistently normal in the relapsing forms. Enhanced vWF fragmentat ion as defined by disappearance of high molecular weight and increase in lo w molecular weight forms was a consistent: finding of the acute phases, and always normalized in remission in all three groups. Unusually large VWF mu ltimers were found exclusively in plasma of relapsing forms of HUS and TTP both during and between relapses. Enhanced levels of vWF:Ag and serum capab ility to induce vWF release in vitro are markers of disease activity and ma y reflect systemic endothelial injury and consequent activation Their prese nce discriminates acute single-episode cases from relapsing farms and, when failing to normalize with plasma therapy, predicts plasma resistance. Enha nced low molecular weight multimers that closely paralleled disease activit y suggest a permissive role of fragmented VWF in the formation of microvasc ular thrombi. Finally, finding of unusually large multimers exclusively in relapsing forms of HUS and TTP even between relapses, when no other clinica l signs of disease activity could be detected, suggests that they cannot be the only factor in microvascular thrombosis.