[The frontline of TMA management]

Thrombotic microangiopathy (TMA) is a pathological condition characterized by platelet thrombi-induced generalized microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. TMA includes the life-threatening diseases thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TTP is different from HUS in that it has a severe deficiency in ADAMTS13 activity. Congenital TTP is caused by a lack of plasma ADAMTS13 activity caused by genetic mutations, and acquired TTP is caused by a secondary deficiency caused by autoantibodies. In Japan the only product approved for the treatment of congenital TTP is fresh frozen plasma containing ADAMTS13. Recombinant ADAMTS13 may provide a new treatment option for congenital TTP. The first-line treatment for acquired TTP is plasma exchange. Rituximab treatment should be considered for patients who are refractory or have relapsed. Caplacizumab is a nanobody that specifically targets von Willebrand factor. ISTH recently published guidelines recommending that caplacizumab be added to the initial treatment for acquired TTP. Atypical HUS (aHUS) is related with the dysregulation of the complement alternative pathway. Eculizumab, a monoclonal antibody that inhibits C5, was the first drug approved for aHUS, and it was found to be well-tolerated by patients and effective in clinical use. TMA is classified based on its etiology, and specific treatments for targeting various etiologies are now available.