Thrombotic thrombocytopenic purpura: a moving target

Almost 80 years after Eli Moschcowitz published the first description of the disease, most patients with idiopathic thrombotic thrombocytopenic purpura (TTP) were found to have acquired autoantibody inhibitors of the ADAMTS13 metalloprotease. Plasma ADAMTS13 normally cleaves von Willebrand factor within nascent platelet-rich thrombi, and ADAMTS13 deficiency allows unchecked thrombus growth to cause microangiopathic hemolysis, thrombocytopenia, and tissue infarction. At present, ADAMTS13 deficiency with a high-titer inhibitor level appears to be associated with an increased risk of early death and subsequent relapse. Thus, acquired ADAMTS13 deficiency identifies a specific mechanism of TTP and is a potential biomarker of disease activity or risk. At present, two major clinical questions in the field may be summarized as follows. First, by emphasizing TTP caused by ADAMTS13 deficiency, are we in danger of neglecting other causes that should be treated with plasma exchange? Second, should we treat asymptomatic patients who have severe ADAMTS13 deficiency to prevent future disease, and if so, how?