The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes: overview of pathogenesis (Experience of The Oklahoma TTP-HUS Registry, 1989-2007)

The Oklahoma TTP (thrombotic thrombocytopenic purpura)-HUS (hemolytic uremic syndrome) Registry, an inception cohort of 382 consecutive patients with TTP-HUS, provides a complete community perspective of these syndromes. TTP is the diagnostic term used for all adults, with or without neurologic or renal abnormalities; it is typically an acquired disorder; it may rarely result from congenital ADAMTS13 deficiency. HUS is the term used for children who have renal failure, most often caused by Escherichia coli O157:H7 infection; it may rarely result from congenital abnormalities of complement regulation. Clinical categories related to associated conditions and potential etiologies provide a structure for describing pathogenesis of the acquired syndromes. (1) Following allogeneic hematopoietic stem cell transplantation; a disorder primarily affecting kidneys described as transplantation-associated thrombotic microangiopathy. (2) Pregnancy-associated; pregnancy is a prominent risk factor for the development of TTP. (3) Drug-associated; acute, immune-mediated systemic syndromes and also dose-dependent renal toxicity. (4) Bloody diarrhea prodrome, suggesting an enteric infectious etiology. (5) Presence of an additional autoimmune disorder. (6) Idiopathic. A severe deficiency of ADAMTS13 activity contributes to the pathogenesis of many idiopathic patients and also some patients who present during pregnancy, with bloody diarrhea, or who have additional autoimmune disorders.