New Concepts of Thrombotic Thrombocytopenic Purpura and a Strategy to Prevent its Relapse

In the past, thrombotic thrombocytopenic purpura (TTP) was defined as a syndrome of the pentad of thrombocytopenia, microangiopathic hemolytic anemia, neurologic deficits, renal abnormalities and fever. To include patients with incomplete features, the pentad definition was replaced by the triad of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and neurologic deficits; or the diad of thrombocytopenia and MAHA. None of these definitions provides a clear distinction of TTP from atypical hemolytic uremic syndrome (aHUS) or other causes of the syndrome of MAHA and thrombocytopenia or thrombotic microanangiopathy. This brief review describes a mechanistic definition of TTP, provides a framework for assessing the role of various co-morbid conditions in the pathogenesis of the syndrome of thrombocytopenia and MAHA, and summarizes new insights of the natural course of TTP. Based on these new insights, a strategy of ADAMTS13-guided preemptive rituximab therapy is proposed to prevent relapses in patients with acquired TTP. Thrombotic thrombocytopenic purpura (TTP) has been defined as a clinical syndrome of pentad (thrombocytopenia, microangiopathic hemolytic anemia [MAHA], neurological deficits, fever and renal abnormalities), triad (thrombocytopenia, MAHA, neurological deficits) or diad (thrombocytopenia and MAHA). In addition to this uncertainty, there was also no consensus on whether and how patients with prominent renal failure or co-morbid conditions should be excluded. The difficulty of defining TTP as a clinical syndrome arises from two facts: More than one disorder may cause the syndrome of diad, triad or pentad; and some patients of TTP do not present with thrombocytopenia or MAHA.