Current management and therapeutical perspectives in thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a particular form of thrombotic microangiopathy typically characterized by microangiopathic hemolytic anemia, profound peripheral thrombocytopenia, and a severe deficiency of the von Willebrand factor-cleaving protease ADAMTS13 (acronym for A Disintegrin And Metalloproteinase with ThromboSpondin-1 motifs [13th member of the family]). ADAMTS13 deficiency is usually severe (<10% of normal activity) and results from autoantibodies directed to ADAMTS13 (acquired TTP) or from biallelic mutations of the encoding gene. In some cases, acquired TTP occurs in association with specific conditions that must be identified for appropriate management: a HIV infection, a connective tissue disease, a pregnancy, a cancer or a treatment with antiplatelet agents. TTP requires a rapid diagnosis and an adapted management in emergency, which allows current remission rates of 80 to 90%. Maximal measures of resuscitation may be required. Daily sessions of therapeutical plasma exchange (TPE) until durable platelet count recovery remain the basis of management of acquired TTP. In the last few years, the anti-CD20 monoclonal antibody rituximab has been increasingly used in patients with a suboptimal response to standard treatment, such as those with refractory disease (∼10% of cases) or an exacerbation of the disease despite intensive TPE (∼50% of cases). Rituximab prevents 1-year but not long-term relapses. Further studies should specify the optimal schedule of rituximab administration and its role as a prophylactic treatment in asymptomatic patients with severe acquired ADAMTS13 deficiency that persists even in disease remission. In hereditary TTP, also known as Upshaw-Schulman syndrome (USS), a diagnosis early in life is mandatory. Prophylactic infusions of plasma should be performed in chronic relapsing forms to prevent long-term organ complications, which have to be assessed accurately and regularly. In the upcoming years, new targeted therapies evaluated through international trials should further improve the management of these diseases. Consensual guidelines for the treatment of very specific and rare situations (such as management during pregnancy in USS patients and prevention of relapses in chronic relapsing acquired TTP) should arise from the shared experience of national groups.