Diagnosis and treatment of TMA based on Japanese clinical guides.

Abstract

Patients with thrombotic microangiopathies (TMAs), which include thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS), and Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS), exhibit multiple symptoms. These include thrombocytopenia (platelet count <15×104/µl), microangiopathic hemolytic anemia (hemoglobin <10 g/dl), and organ damage, such as renal dysfunction or neurological abnormalities. Guidelines for the management of TTP, aHUS, and STEC-HUS have been published. Diagnosis of TTP, STEC-HUS, or aHUS requires ADAMTS13 activity <10%, the detection of STEC or Shiga toxins, or a genetic analysis to investigate the complement regulatory system, respectively. In the established management of TMAs, fresh frozen plasma is used for congenital TTP to supplement ADAMTS13. Plasma exchange (PE) is used in acquired TTP (ATTP) to remove inhibitors and replace ADAMTS13. Steroid therapy is administered in ATTP to suppress inhibitor production, and rituximab is administered in ATTP without response to PE or with high titers of ADAMTS13 inhibitors. Eculizumab, a monoclonal antibody for complement protein 5, is used for the treatment of aHUS. Supportive therapy is required for some TMAs, particularly STEC-HUS, but platelet transfusion is generally contraindicated for other TMAs, such as TTP. Treatments should be administered in accordance with these guidelines to improve the outcome of TMAs.