Potential Role of ADAMTS13/FXI Complexes in the Pathogenesis of End Stage Renal Disease.

ADAMTS13 alternatively known as von Willebrand Factor (vWF) cleaving protease is a Zinc metalloprotease which cleaves macromolecular M-vWF multimers at the Tyr (1605)-Met (1606) bond located in the AT domain of vWF. Down regulation of ADAMTS13 is known to be associated with thrombotic thrombocytopenic purpura (TTP). ADAMTS13 forms stable complex with factor XI and factor XIa. Measurement of ADAMTS13/FXI complexes in plasma may provide additional information on the pathogenesis of ESRD associated thrombotic complications. ADAMTS13/FXI can be measured using an ELISA based immunoassay. A polyclonal antibody reacts with a peptide in C-terminal region of the ADAMTS13 molecule is quoted on the micro titer plate. ADAMTS13 present in these test samples bind the antibody. After washing the bound ADAMTS13/FXI complexes were quantified. To test the hypothesis that ADAMTS13 levels are altered in ESRD, blood samples from 62 patients with ESRD prior to dialysis session were collected. Control group comprised of 34 normal healthy age match controls. The vWF antigen levels were also measured in both the groups using an ELISA method. The ESRD group exhibited a marked variation in the ADAMTS13/FXI complex levels with a range of 0 to 1100% (mean = 161±315) of the 62 samples. Eleven patients exhibited a greater than 250% where as the 51 patients exhibited less than 100 % complex. The distribution of ADMTS13/FXI complex was bi-modal. In the normals, the ADAMTS13/FXI complex activity ranges from 147–201% with a mean of 169±16. Unlike the ESRD population the normal group exhibited guassian distribution. The vWF antigen levels relatively higher in the ESRD patients (175±30) vs the normal (88±19). These results suggest that ADAMTS13/FXI is dysregulated in ESRD patients. While most of the patients exhibit a marked decrease in ADAMTS13 level, some of these patients exhibit markedly higher levels. Such fluctuation in the ADAMTS13/FXI level may contribute to the potential thrombotic and bleeding complications in ESRD pathogenesis.