Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS): the new thinking. Liu J, Hutzler M, Li C, Pechet L. Journal of Thrombosis and Thrombolysis 2001;11(3):261-272.

ABSTRACT:

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are two disorders with many similarities. Though their first descriptions appeared at different time in history, there has been a trend among physicians to consider them as the same clinical entity. However, in recent years new research findings on the pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome have revealed some differences between the two disorders. This paper reviews the current approaches to the clinical and laboratory diagnosis of TTP and HUS, as well as therapeutic strategies. Also described are the recent advances in three areas in the study of the pathophysiology of TTP and HUS, namely the newly discovered von Willebrand factor multimer-cleaving protease, endothelial cell apoptosis induced by serum from patients with TTP and atypical HUS, and the activation of complement system. Since distinguishing and differentiating between TTP and HUS may help to develop more effective therapies targeted at key steps of the disease development, possible ways of reclassifying the TTP-HUS disorders are discussed. These are: 1) metalloprotease deficient vs. metalloprotease non-deficient TTP-HUS; 2) apoptosis positive vs. apoptosis negative TTP-HUS; and 3) complement activation (alternative pathway) found in sporadic HUS. In the first group, classical TTP patients are categorized as metalloprotease deficient and classical HUS (diarrhea-associated HUS in children and adults) patients are nondeficient. In the second grouping, plasma from idiopathic TTP and nondiarrheal HUS patients induced cell death in small blood vessels of many tissues except lung tissue, while plasma from childhood/diarrhea-associated HUS patients did not. In the third group, those with normal complement levels and those with decreased complement levels are distinguished; complement levels reflect the activity of antibody and blood clotting proteins. Understanding and identifying these factors, and their relationship to TTP would assist in the development of therapies and decision-making regarding appropriate therapy for TTP-HUS.