Thrombotic Thrombocytopenic Purpura and atypical Haemolytic‐Uremic Syndrome: current management issues

Thrombotic hromocyopenic purpura(TTP) is a life‐threatening thrombotic disorder in which platelet/von Willebrand factor deposits occur in the microcirculation of many organs including the brain, kidney, heart and abdominal viscera. A related thrombotic microangiopathy, atypical Hemolytic‐Uremic Syndrome(aHUS), is characterized by platelet/fibrin deposition predominantly in the kidneys, with acute renal failure as the major presenting clinical manifestation. Key advances in understanding the pathophysiology of these disorders now allow a better classification, with ADAMTS13 deficiency associated with TTP and defects in complement regulating proteins or complement factors identified in aHUS. Therapeutic plasma exchange has markedly improved mortality in TTP from more than 90% in the past to 10% to 20% currently. Immunosuppressive therapy with corticosteroids and the anti‐CD20 monoclonal antibody rituximab has assumed even greater importance in the management of TTP patients with autoantibodies to ADAMTS13. Although plasma exchange is also useful in aHUS, the advent of the anti‐C5 complement pathway inhibitor eculizumab promises to further improve clinical outcomes in these patients.