[Thrombotic thrombocytopenic purpura]

Abstract

Thrombotic thrombocytopenic purpura (TTP) is the most extensive and dangerous intravascular platelet clumping disorder. For more than a half-century after its initial recognition, mortality was near 100% and the etiology totally obscure. Then, in the late 1970s to early 1980s, empiric, but successful, therapy with plasma exchange was followed by sudden laboratory insight into pathophysiology. The most important finding was the identification of a novel metalloprotease, named ADAMTS13, which is involved in the regulation of the size of von Willebrand factor. Inherited or acquired deficiencies of ADAMTS13 impair von Willebrand factor cleavage, leading to the disseminated formation of platelet-rich thrombi in the microcirculation and to symptoms of end-organ ischemia. Treatment with plasma exchange, available for more than 20 years, has dramatically altered the course of disease in adults with TTP. Long term follow-up has revealed increasing frequencies of relapse that require new therapeutic alternatives for these patients.