THE ARGININE NITRIC-OXIDE PATHWAY IN THROMBOTIC MICROANGIOPATHY

Eleven patients with thrombotic thrombocytopenic purpura (TTP) or haem olytic uremic syndrome (HUS) were investigated with respect to plasma concentrations of L-arginine, a substrate for nitric oxide (NO) and as ymmetrical dimethyl arginine (ADMA), during active disease and after r ecovery. Plasma concentration of NO;, the degradation product of NO, w as also analyzed. The patients were treated with fresh-frozed plasma a nd plasmapheresis. One of the patients had experienced relapses of TTP five times during the preceeding year. After treatment with p.o. argi nine hydrochloride 1.5 g x 3 was started, no relapse has occurred duri ng a 12-month period. During the active phase the plasma concentration of arginine was low and that of NO3- was very high, indicating a high NO-synthesis rate. The arginine concentration normalized on recovery. Plasma levels of ADMA, was twice normal during active disease, and di d not return to normal on recovery. In conclusion, patients with TTP/H US exhibit signs of activation of the NO-synthesis.