Thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies

Abstract

Thrombotoic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterised by systemic platelet aggregation, organ ischaemia, profound thrombocytopenia (with increased marrow megakaryocytes) and fragmentation of erythrocytes. Haemolytic-uraemic syndrome (HUS) is another type of thrombotic microangiopathy accompanied by renal dysfunction. In adults, a thrombotic microangiopathy that clinically more often resembles HUS than TTP may follow: bone marrow or solid organ transplantation and immunosuppression with cyclosporine or tacrolimus; total-body irradiation; mitomycin; gemcitabine; multiple chemotherapeutic agents; or antiangiogenic/antineoplastic substances. This article discusses the thrombotic microangiopathies that have provided the most extensive molecular insights to date into pathophysiology. These are familial and acquired forms of TTP associated with deficient plasma von Willebrand factor (VWF)-cleaving metalloprotease (ADAMTS-13) activity; acquired diarrhoea-associated HUS; the thrombotic microangiopathies associated with cyclosporine/tacrolimus or bevacizumab; and the preeclampsia-HELLP (haemolysis-elevated liver enzymes-low platelets) syndrome.