Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome: Pathogenesis and Therapy

Abstract

Thrombotic thrombocytopenia purpura (TTP) and hemolytic uremia syndrome (HUS) are rare and closed-related disorders with similar clinical features. They are characterized by thrombocytopenia and microangiopathic hemolytic anemia in different severity. TTP was conventionally described as a pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal involvement and fever. HUS affects mainly children and presents with microangiopathic hemolytic anemia, thrombocytopenia and a clinical picture dominated by renal insufficiency. Clinically, various denominations have been used to describe these similar syndromes with variable combinations of neurologic and renal manifestations. Because of without definitive pathogenetic evidence to support a clear distinction among the various clinical entities, some given such disorders the generic term TTP-HUS. In a recent decade, the pathogenesis of those disorders have been described: First, defective regulation of von Willebrand factor activity by a severe deficiency of A Disintegrin and Metalloprotease with ThromboSpondin, type I repeat, member 13 (ADAMTS13) is found in most patients with congenital and acquired idiopathic TTP. Second, mutations in the genes for complement proteins, including Complement 3, factor H, B and I, and membrane cofactor protein are associated with disregulation of alternative complement pathway in many patients with Atypical HUS. These advances, along with well-known association between Shiga toxins and Diarrhea positive HUS (D^+ HUS), provide the better understanding of variable disease processes and the further directions of diagnosis and treatment in TTP-HUS. TTP in adult typically follow a progressive course, irreversible renal failure, progressive neurologic deterioration, cardiac ischemia, and death are common outcome. Plasma exchange is associated with a high response rate, therefore, aggressive plasma exchange should be initiated in all patients as soon as the clinical dyad of microangiopathic hemolytic anemia & thrombocytopenia present.