[Diagnosis and management of thrombotic microangiopathies]

Thrombotic microangiopathies (TMAs) are microvascular occlusive disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia, and systemic or intrarenal aggregation of platelets. TMA includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). It is now well known that TTP is caused by deficiency of ADAMTS13 activity due to mutations in the ADAMTS13 gene (Upshaw-Schulman syndrome, USS) or by acquired autoantibodies against ADAMTS13. On the other hand, more than 90% of HUS cases are associated with Shiga toxin-producing E. coli infection. The remaining 10% of patients have what is called atypical HUS (aHUS). Most aHUS cases are caused by uncontrolled complement activation due to genetic mutations in the alternative pathway, such as complement factor H, complement factor I, membrane cofactor protein (CD46), and C3. TMAs also develop in association with various underlying diseases and conditions (so-called secondary TMA) including connective tissue disorders, transplantation (hematopoietic stem cell, liver, kidney), malignancy, pregnancy, and certain drugs. Plasma exchange is the first-line therapy for most patients with TMAs. Early plasma exchange improves TMA outcomes. Monoclonal therapies, rituximab in TTP and eculizumab in aHUS, are now frequently being used as second-line treatment options.