Practical aspects of diagnosis and treatment of thrombotic thrombocytopenic purpura
Abstract
Thrombotic thrombocytopenic purpura (TTP) is characterized by a triad of symptoms: thrombocytopenia, hemolytic anemia and organ dysfunction due to disturbed microcirculation. TTP is caused by severe deficiency of a plasma metalloprotease, ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs 13) either due to congenital defects in the ADAMTS13 gene (congenital TTP) or development of autoantiobodies against ADAMTS13 (acquired TTP). Organ dysfunction is life threatening and may lead to death unless patients are immediately applied a therapy of plasma exchange (PEX). Initial diagnosis of TTP is based on clinical symptoms of ischemic organ injury, thrombocytopenia and hemolytic anemia with negative Coombs test and schistocytes in blood smear. Suspected TTP requires collection of pretreatment samples for measurement of ADAMTS3 activity and level of anti-ADAMTS13 autoantibodies. PEX should be initiated as soon as possible, even before the results of ADAMTS13 activity and anti-ADAMTS13 autoantibodies become available. ADAMTS13 activity below 5–10% with the presence of ADAMTS13 autoantibodies confirms the diagnosis of acquired TTP and daily PEX in combination with immunosuppressive treatment (corticosteroids) should be continued. Diagnosis of congenital TTP is confirmed by low ADAMTS13 activity in the absence of autoantibodies to ADAMTS13. Congenital TTP is usually treated with infusions of fresh frozen plasma to substitute the missing enzyme.
Keywords: thrombotic thrombocytopenic purpuraADAMTS13Upshaw-Schulman syndromeschistocytesplasma exchangeimmunosuppression
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