Thrombotic Thrombocytopenic Purpura and Other Thrombotic Microangiopathic Hemolytic Anemias

Abstract

Thrombotic microangiopathies (TMAs) include several diseases, most prominently thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) characterized by profound thrombocytopenia and microangiopathic hemolytic anemia. Usually congenital TTP is due to mutations in the gene ADAMTS13 or idiopathic when autoantibodies against ADAMTS13 are defined. The differential diagnosis of TTP from other TMAs can be sometimes challenging even with the discovery of ADAMTS13 for more than a decade. The presence of ADAMTS13 activity does not rule out TTP and ultra-large von Willebrand factor (ULVWF) multimers not always present in plasma of patients with TTP. Pathogenesis of TTP is related to massive intravascular aggregation of platelets as a result of lack of degradation of ULVWF multimers because of a lack of ADAMTS13 or secretion of excessive ultra-large multimers by endothelial cells. Diagnostic criteria of TTP are based on clinical features of neurological and renal disfunction along with hemolytic anemia, severe thrombocytopenia, low ADAMTS13 activity, and mutation in ADAMTS13 gene when congenital TTP is suspected. The standard treatment of TTP includes plasma exchange or plasma infusion. Splenectomy, protein A immunoadsorbtion, immunosuppressive drugs, and CD20 antibodies against B cells like rituximab are also used. Recombinant ADAMTS13 in congenital TTP is still to be used only in clinical trials. In HUS plasmapheresis is not efficient. Treatment of other TMA diseases is based on their underlying conditions.