We investigated a patient with atypical hemolytic uremic syndrome without diarrhea to determine the presence of antibodies and the specificity of the related antigens. The patient experienced repeated episodes of hemolytic uremic syndrome. She is dialysis dependent. von Willebrand factor (vWF), vWF multimers, platelet aggregation, ADAMTS-13 activity and platelet immunoblots were determined. During acute episodes vWF increased threefold, with unusually large vWF multimers on two occasions. Platelet aggregation was normal but the plasma caused spontaneous aggregation of normal platelets. Reactivity was removed after absorption with protein A. Protein blotting against platelet and microvascular endothelial cells showed strong and persistent reactivity against antigens of 200 and 55 kDa. Two-dimensional immunoblots of the whole platelet proteome and incubation with plasma identified strong immunoreactivity with two target spots in the 55-kDa area. Mass spectroscopy confirmed the target as beta-fibrin, molecular weight 50.73 kDa, isoelectric point 7.95, with MASCOT scores of 859 and 750, Two years after presentation another band was detected at 66 kDa and identified as the alpha subunit of fibrin. This patient's plasma contained a platelet-aggregating factor that was removed by immunoglobulin absorption. She developed antibodies against the alpha and beta subunits of fibrin/fibrinogen.