Thrombotic microangiopathy in a 17-year-old patient: TTP, HUS or a bit of both?

Abstract

Thrombotic microangiopathies are characterized by the development of hyaline thrombi in small vessels resulting in thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. Thrombotic-thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are two major clinical syndromes of thrombotic microangiopathies. Although differential diagnosis between TTP and HUS is commonly determined in the clinical setting, recent evidence suggests major pathophysiological differences between the two diseases. Autoimmune inhibitors or genetic mutations of a von Willebrand factor (VWF) cleaving metalloprotease (ADAMTS13) leads to the accumulation of unusually large multimeric forms of VWF in TTP, facilitating adherence of platelets and development of microthrombi. In contrast, classic HUS is caused by infection with verocytotoxin-producing bacteria. This toxin induces endothelial injury, apoptosis and inflammation. Endothelial injury results in increased shear-stress, fostering cleavage of VWF, but thrombosis eventually develops. One would assume that measurement of ADAMTS13 activity and/or detection of verocytotoxin could easily contribute to the differential diagnosis of TTP or HUS. We report on a case of a young patient with thrombotic microangiopathy and renal involvement with low ADAMTS13 concentrations which did not respond well to plasmapheresis therapy, but subsequent to the detection of verocytoxin producing E. coli with the serotype O157:H7, reacted well to antibiotic treatment. Sequencing of the ADAMTS13 gene revealed no mutations and no anti-ADAMTS13 antibodies could be detected. This case shows overlapping presentations as well as etiologies for both TTP and HUS, a finding also underscored by a recent animal model in which verocytoxin triggered development of TTP in ADAMTS13-deficient mice.